Brs Pharmacology (Board Review)

Name: Sulfisoxazole (Gantrisin) Class: Sulfonamide

Name: Sulfamethoxazole (Gantanol) Class: Sulfonamide

Mech.: Comp. inhib. of PABA incorp. into dihydropteric acid → inhib. of folic acid. Bacteriostatic. Absorption: Rapidly absorbed in GI tract. Parenteral. Distribution: Widely distrib; CSF. Crosses placenta. Metab.: Acetylated in liver Excretion, t_: Renal filtration, secretion Toxicity/S.E.s: Hypersensitivity—fever, rash, photosensitivity; UT disturbances— deposition of crystalline aggregates; hematopoetic disorders—dyscrasias Utility: Uncomplicated UTIs, trachoma (contag. disease of eyelid, conjunct, cornea), nocardiosis (tuberculosis-like infect.), prophylaxis (burnt skin, suppressing recurring UTIs, rheumatic fever) Special Features: Spectrum—gram +, gram -. Less renal toxicity than other sulfas. Protoype.

Mech.: Comp. inhib. of PABA incorp. into dihydropteric acid → inhib. of folic acid. Bacteriostatic. Absorption: Rapidly absorbed in GI tract (slower than isoxazole). Parenteral. Distribution: Widely distrib; limited CSF. Crosses placenta. Metab.: Acetylated in liver Excretion, t_: Renal filtration, secretion Toxicity/S.E.s: Hypersensitivity—fever, rash, photosensitivity; UT disturbances— deposition of crystalline aggregates; hematopoetic disorders—dyscrasias Utility: Uncomplicated UTIs, trachoma (contag. disease of eyelid, conjunct, cornea), nocardiosis (tuberculosis-like infect.), prophylaxis (burnt skin, suppressing recurring UTIs, rheumatic fever) Special Features: Spectrum—gram +, gram -.

Name: Sulfadiazine Class: Sulfonamide

Name: Sulfasalazine (Azulfidine) Class: Sulfonamide

Mech.: Comp. inhib. of PABA incorp. into dihydropteric acid → inhib. of folic acid. Bacteriostatic. Absorption: Rapidly absorbed in GI tract. Parenteral. Distribution: Widely distrib; good CSF. Crosses placenta. Metab.: Acetylated in liver Excretion, t_: Renal filtration, secretion Toxicity/S.E.s: Hypersensitivity—fever, rash, photosensitivity; UT disturbances— deposition of crystalline aggregates; hematopoetic disorders—dyscrasias Utility: Uncomplicated UTIs, trachoma (contag. disease of eyelid, conjunct, cornea), nocardiosis (tuberculosis-like infect.), prophylaxis (burnt skin, suppressing recurring UTIs, rheumatic fever) Special Features: Spectrum—gram +, gram -.

Mech.: Comp. inhib. of PABA incorp. into dihydropteric acid → inhib. of folic acid. Absorption: Poorly absorbed in GI tract. Distribution: GI tract Metab.: Hydrolized to active form by intest. bacteria. Excretion, t_: feces

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Toxicity/S.E.s: Interferes w/normal flora → ↓ vit. K synth. Utility: Active in bowel lumen. Used prior to surgery to reduce microbe population. Treat inflammatory bowel disease, rheumatoid arthritis Special Features: Broken down in intestines to liberate 5-aminosalicylate (antiinflammatory).

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Name: Silver Sulfadiazine (Silvadene) Class: Sulfonamide

Name: Sulfacetamide sodium (Sulamyd Sodium) Class: Sulfonamide

Mech.: Releases silver → toxicity for bacteria and fungi.

Mech.: Comp. inhib. of PABA incorp. into dihydropteric acid → inhib. of folic acid. Absorption: Distribution: Ophthalmic application. Penetrates into ocular fluids at high conc. Metab.: Excretion, t_: Toxicity/S.E.s: Utility: Ophthalmic infections Special Features: High aqueous concentrations are not irritating.

Absorption: Distribution: Topical Metab.: Excretion, t_: Toxicity/S.E.s: Utility: Used topically to reduce infection of burns, but not to treat established infections. Special Features:

Name: Trimethoprim-Sulfamethoxazole (Bactrim, Septra) Class: Mech.: Acts on two sequential steps in synth of folic acid. PABA competitive inhib, dihydrofolate reductase inhib. Bacteriostatic. Absorption: Oral, IV Distribution: Metab.: Excretion, t_: Toxicity/S.E.s: Megaloblastic anemia, leukopenia, granulocytopenia (prevented by admin. of folic acid) Utility: Uncomp. UTIs, otitis media, acute exacerbations of chronic bronchitis, various pneumonias. DOC for Travelers’ diarrhea, P. carinii pneumonia, Shigella enteritis, systemic Salmonella infects, prostatitis. Special Features: Trimethoprim = highly selective inhib. of bacterial dihydrofolate reductase.

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Name: Chloramphenicol (Chloromycetin) Class: Mech.: Bacteriostatic. Inhib protein synth by binding to 50S subunit. Absorption: Rapid oral absorption Distribution: Body fluids, good CSF. Crosses placenta. Milk. Metab.: Liver (glucuronyl transferase) Excretion, t_: Urine (filtration, secretion), 1.5-3.5 hr. Toxicity/S.E.s: Bone marrow depression (anemia, leukopenia, thrombocytopenia, prob. due to inhib. of mitoch. protein), aplastic anemia (allergic/idiosync, rare, irreversible, often fatal), Gray Baby Syndrome (neonate overdose due to reduced ability to conjuate CA and secrete metabolites), superinfection (S. aureus, Pseudomonas, fungi, can be life threatening). Utility: DOC for severe Bacteroides infects (esp. CNS), backup for memingitis, rickettsial infects, brucellosis. Special Features: Never use if safer antibiotic avail. Never use for mild infects.

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Name: Tetracycline (Achromycin V) Class: Tetracycline Mech.: Active uptake into bacteria →inhib protein synth by binding to 30S ribosome. Bacteriostatic Absorption: Oral adequate, but incomplete. Impaired by divalent cations. IM painful. IV may cause thrombophlebitis. Never intrathecal. Distribution: Good CSF. Conc. in liver → enterohepatic circ. Penetrates most tissues and fluids. Crosses placenta. Metab.: Excretion, t_: filtration (1°), bile Toxicity/S.E.s: GI — burning, discomfort, nausea, vomitiing; superinfection — due to broad spectrum, candida albicans (1°), staph enterocolitis, pseudomemb. colitis; hepatotoxicity (esp. in pregnancy); renal toxicity; Fanconi synd.; perm. brown discoloration of teeth; slowing of bone growth; phototoxicity; thrombophlebitis; hematopoetic changes; rare hypersens. rxns.

Name: Doxycycline (Vibramycin) Class: Tetracycline Mech.: Active uptake into bacteria →inhib protein synth by binding to 30S ribosome. Bacteriostatic Absorption: Good oral absorption. Impaired by divalent cations. IM painful. IV may cause thrombophlebitis. Never intrathecal. Distribution: Good CSF. Conc. in liver → enterohepatic circ. Penetrates most tissues and fluids. Crosses placenta. Metab.: Excretion, t_: bile; doesn’t require renal excretion

Toxicity/S.E.s: GI — burning, discomfort, nausea, vomitiing; superinfection — due to broad spectrum, candida albicans (1°), staph enterocolitis, pseudomemb. colitis; hepatotoxicity (esp. in pregnancy); renal toxicity; Fanconi synd.; perm. brown discoloration of teeth; slowing of bone growth; phototoxicity (more than others); thrombophlebitis; hematopoetic changes; rare hypersens. rxns.

Utility: gram - cocci, gram - bacilli, acid fast bacilli, chlamydiae, mycoplasma, rickettsia, spirochetes. No effect on viruses or fungi. Also used for acne, prophylaxis for Travelers’ diarrhea. Special Features: Broad spectrum. Decreased effect of oral contraceptives.

Utility: gram - cocci, gram - bacilli, acid fast bacilli, chlamydiae, mycoplasma, rickettsia, spirochetes. No effect on viruses or fungi. Also used for acne, prophylaxis for Travelers’ diarrhea. Special Features: Broad spectrum. Decreased effect of oral contraceptives.

Name: Minocyclin (Minocin) Class: Tetracycline Mech.: Active uptake into bacteria →inhib protein synth by binding to 30S ribosome. Bacteriostatic Absorption: Good oral absorption. Impaired by divalent cations. IM painful. IV may cause thrombophlebitis. Never intrathecal. Distribution: Good CSF. Conc. in liver → enterohepatic circ. Penetrates most tissues and fluids. Also enters tears and saliva. Crosses placenta. Metab.: Liver, but not critical. Excretion, t_: bile; doesn’t require renal excretion

Name: Penicillin G Class: Penicillin (Penicillin G-related) Mech.: Binds to PBPs, blocks activity of transpeptidases in terminal stages of cell wall formation. Bactericidal. Absorption: Erratic (30%). Usu. not used orally. I.M or I.V. Prolonged effect with repository preparations (procaine, benzathine (longest)) deep IM. Distribution: Widely distributed, little CSF unless meninges inflamed. Metab.: Excretion, t_: Rapidly elim. by kidneys (probenecid blocks excretion), small amt. in bile. Toxicity/S.E.s: hypersensitivity (1-10%), painful injection, epilepsy, superinfection. Utility: Many gram +, anaerobes, and a few gram -. Most staph. and gram resistant. Prophylactic use (rheumatic fever, strep. infections). Special Features: Narrow spectrum.

Toxicity/S.E.s: Vestibular toxicity; GI — burning, discomfort, nausea, vomitiing; superinfection — due to broad spectrum, candida albicans (1°), staph enterocolitis, pseudomemb. colitis; hepatotoxicity (esp. in pregnancy); renal toxicity; Fanconi synd.; perm. brown discoloration of teeth; slowing of bone growth; phototoxicity; thrombophlebitis; hematopoetic changes; rare hypersens. rxns.

Utility: gram - cocci, gram - bacilli, acid fast bacilli, chlamydiae, mycoplasma, rickettsia, spirochetes. No effect on viruses or fungi. Also used for acne, prophylaxis for Travelers’ diarrhea. Special Features: Broad spectrum. Decreased effect of oral contraceptives.

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Name: Penicillin V Class: Penicillin (Penicillin G-related) Mech.: Binds to PBPs, blocks activity of transpeptidases in terminal stages of cell wall formation. Bactericidal. Absorption: Acid stable → good oral absortption. Distribution: Widely distributed, little CSF unless meninges inflamed. Metab.: Excretion, t_: Rapidly elim. by kidneys (probenecid blocks excretion), small amt. in bile. Toxicity/S.E.s: : hypersensitivity (1-10%), superinfection. Utility: Mild to moderate infections only: Many gram +, anaerobes, and a few gram -. Most staph. and gram - resistant. Same spectrum as Pen. G, but less active. Special Features: Narrow spectrum.

Name: Methicillin (Staphcillin) Class: Penicillin (Penicillinase-resistant) Mech.: Binds to PBPs, blocks activity of transpeptidases in terminal stages of cell wall formation. Bactericidal. Absorption: Usu. IV for seious infections. IM. Distribution: Widely distributed, little CSF unless meninges inflamed. Metab.: Excretion, t_: Rapidly elim. by kidneys (probenecid blocks excretion), small amt. in bile. Toxicity/S.E.s: hypersensitivity (1-10%), superinfection. Utility: Penicillinase-producing staph. infections. Gram +. Special Features: Narrow spectrum.

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Name: Nafcillin (Nafcil) Class: Penicillin (Penicillinase-resistant) Mech.: Binds to PBPs, blocks activity of transpeptidases in terminal stages of cell wall formation. Bactericidal. Absorption: Poor oral. Usu. IV for seious infections. IM. Distribution: Widely distributed, little CSF unless meninges inflamed. Metab.: Excretion, t_: Rapidly elim. by kidneys (probenecid blocks excretion), small amt. in bile. Toxicity/S.E.s: hypersensitivity (1-10%), superinfection. Utility: Penicillinase-producing staph. infections. Gram +. Special Features: Narrow spectrum. Prob. most effective penicillinase-resist.

Name: Oxacillin (Bactocill) Class: Penicillin (Penicillinase-resistant) Mech.: Binds to PBPs, blocks activity of transpeptidases in terminal stages of cell wall formation. Bactericidal. Absorption: Acid stable. Absorbed orally. IM, IV. Distribution: Widely distributed, little CSF unless meninges inflamed. Metab.: Excretion, t_: Rapidly elim. by kidneys (probenecid blocks excretion), small amt. in bile. Toxicity/S.E.s: hypersensitivity (1-10%), superinfection. Utility: Penicillinase-producing staph. infections. Mild infections. Special Features: Narrow spectrum.

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Name: Ampicillin (Omnipen, Polycillin) Class: Penicillin (Aminopenicillin) Mech.: Binds to PBPs, blocks activity of transpeptidases in terminal stages of cell wall formation. Bactericidal. Absorption: Acid stable. Good oral, but food interferes. IM, IV. Distribution: Widely distributed, little CSF unless meninges inflamed. Metab.: Excretion, t_: Rapidly elim. by kidneys (probenecid blocks excretion), small amt. in bile. Toxicity/S.E.s: diarrhea, non-allergy skin rash, hypersensitivity (1-10%), superinfection. Utility: More effective against gram -s (esp. Proteus, H. influenzae, E. coli, P. mirabilis). Less active than Pen. G against gram+ cocci. Special Features: Broad spectrum.

Name: Amoxicillin (Amoxil) Class: Penicillin (Aminopenicillin) Mech.: Binds to PBPs, blocks activity of transpeptidases in terminal stages of cell wall formation. Bactericidal. Absorption: Acid stable. Good oral (better than ampicillin). Distribution: Widely distributed, little CSF unless meninges inflamed. Metab.: Excretion, t_: Rapidly elim. by kidneys (probenecid blocks excretion), small amt. in bile. Toxicity/S.E.s: diarrhea (less than ampicillin), hypersensitivity (1-10%), superinfection. Utility: More effective against gram -s (esp. Proteus, H. influenzae, E. coli, P. mirabilis). Less active than Pen. G against gram+ cocci. Special Features: Broad spectrum.

Name: Ticarcillin (Ticar) Class: Penicillin (Extended spectrum) Mech.: Binds to PBPs, blocks activity of transpeptidases in terminal stages of cell wall formation. Bactericidal. Absorption: IM, IV. Distribution: Widely distributed, little CSF unless meninges inflamed. Metab.: Excretion, t_: Rapidly elim. by kidneys (probenecid blocks excretion), small amt. in bile. Toxicity/S.E.s: hypersensitivity (1-10%), superinfection., coagulation disorders. Utility: Gram -. Effective against Pseudomonas, Proteus mirabilus, often used w/aminoglyc. Special Features: Narrow spectrum. Resistance develops quickly.

Name: Clavulanic acid

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Class: β-Lactamase Inhibitor Mech.: inhibits some β-lactamases Absorption: Distribution: Metab.: Excretion, t_: Toxicity/S.E.s: Utility: Combined with amoxicillin (Augmentin) to increase efficacy against penicillinase-producing bacteria (i.e., staph.) Special Features:

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Name: Sulbactam

Absorption: Distribution: Metab.: Excretion, t_: Toxicity/S.E.s: Utility: Combined with ampicillin (Unasyn-sulbactam) to increase efficacy against penicillinase-producing bacteria (i.e., staph). Special Features:

Name: Probenecid Class: Mech.: Interferes w/renal excretion of drugs that undergo tubular secretion. Inhib. glucuronide conjugation of other drugs. Absorption: Distribution: Metab.: Excretion, t_: Toxicity/S.E.s: Utility: Special Features: Decreases renal excretion of methotrexate — possible toxicity. Decreases renal excretion of penicillin.

Name: Cephalothin (Keflin) Class: First Gen. Cephalosporin Mech.: Binds to PBPs, blocks activity of transpeptidases in terminal stages of cell wall formation. Bactericidal. Absorption: IV. IM rarely used due to pain. Distribution: Poor CSF. Metab.: Excretion, t_: Toxicity/S.E.s: Hypersensitivity (some cross-sensitivity to pen.), superinfection, renal damage (worse if comb. w/aminoglycs.) Utility: Usu not DOC. Serious Klebsiella infects., strep/staph infects, some penicillinase-producing bacteria. Special Features: Narrow spectrum. Greater gram - activity than pen. G. More gram+ activity than gram - activity. Less susceptible to βlactamase than most penicillins.

Name: Cephalexin (Keflex) Class: First Gen. Cephalosporin Mech.: Binds to PBPs, blocks activity of transpeptidases in terminal stages of cell wall formation. Bactericidal. Absorption: Oral. Distribution: Poor CSF. Metab.: Excretion, t_: Toxicity/S.E.s: Hypersensitivity (some cross-sensitivity to pen.), superinfection, renal damage (worse if comb. w/aminoglycs.) Utility: Usu not DOC. Serious Klebsiella infects., strep/staph infects, some penicillinase-producing bacteria. Special Features: Narrow spectrum. Greater gram - activity than pen. G. More gram+ activity than gram - activity. Less susceptible to βlactamase than most penicillins.

Class: β-Lactamase Inhibitor Mech.: inhibits some β-lactamases

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Name: Cefoxitin (Mefoxin) Class: Second Gen. Cephalosporin Mech.: Binds to PBPs, blocks activity of transpeptidases in terminal stages of cell wall formation. Bactericidal. Absorption: IV. IM rare due to pain. Distribution: Poor CSF. Metab.: Excretion, t_: Toxicity/S.E.s: Hypersensitivity (some cross-sensitivity to pen.), superinfection, renal damage (worse if comb. w/aminoglycs.) Utility: Mixed anaerobic infects. Special Features: More gram- efficacy than first gen. Less gram+ cocci efficacy than first gen. ↑ β-lactamase resistance.

Name: Cefaclor (Ceclor) Class: Second Gen. Cephalosporin Mech.: Binds to PBPs, blocks activity of transpeptidases in terminal stages of cell wall formation. Bactericidal. Absorption: Oral. Distribution: Poor CSF. Metab.: Excretion, t_: Toxicity/S.E.s: Hypersensitivity (some cross-sensitivity to pen.), superinfection, renal damage (worse if comb. w/aminoglycs.) Utility: Resp. and middle ear infections (H. influenzae, M. catarrhalis) Special Features: More gram- efficacy than first gen. Less gram+ cocci efficacy than first gen. ↑ β-lactamase resistance. Problem w/bacterial resistance.

Name: Cefotaxime (Claforan) Class: Third Gen. Cephalosporin Mech.: Binds to PBPs, blocks activity of transpeptidases in terminal stages of cell wall formation. Bactericidal. Absorption: IV Distribution: good CSF Excretion, t_: Toxicity/S.E.s: Hypersensitivity (some cross-sensitivity to pen.), superinfection, renal damage (worse if comb. w/aminoglycs.) Utility: Serious nosocomial gram- sepsis. Meningitis caused by gram- enteric bacteria or H. influenzae. Serious Klebsiella infects., strep/staph infects, some penicillinase-producing bacteria. Nosocomial infects. Often used in comb. w/aminoglycosides. Special Features: Decreased efficacy against gram+ cocci. Broader gramspectrum. More resistance against β-lactamases than second generation. Problem w/bacterial resistance.

Name: Cefixime (Suprax) Class: Third Gen. Cephalosporin Mech.: Binds to PBPs, blocks activity of transpeptidases in terminal stages of cell wall formation. Bactericidal. Absorption: Oral Distribution: poor CSF Excretion, t_: Toxicity/S.E.s: Hypersensitivity (some cross-sensitivity to pen.), superinfection, renal damage (worse if comb. w/aminoglycs.) Utility: Serious nosocomial gram- sepsis. Serious Klebsiella infects., strep/staph infects, some penicillinase-producing bacteria. Nosocomial infects. Often used in comb. w/aminoglycosides. Special Features: Decreased efficacy against gram+ cocci. Broader gramspectrum. More resistance against β-lactamases than second generation. Problem w/bacterial resistance.

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Name: Imipenem

Name: Aztreonam (Azactam)

Class: β-lactam (Carbapenem)

Class: β-lactam (Monobactam)

Mech.: Binds to PBPs, blocks activity of transpeptidases in terminal stages of cell wall formation. Bactericidal. Absorption: Oral, IV (painful) Distribution: Metab.: Excretion, t_: Toxicity/S.E.s: painful injection, allergy, nausea/vomiting, superinfection (diarrhea), reversible blood disorders. Utility: Combined w/equal amts of cilastatin to block tubular metab. and formation of nephrotoxic compounds. Treats serious nosocomial infections, infections of unknown etiology, mixed infections.

Mech.: Binds to PBPs, blocks activity of transpeptidases in terminal stages of cell wall formation. Bactericidal. Absorption: Distribution: Metab.: Excretion, t_: Toxicity/S.E.s: Gram+ superinfections. Utility: Infections caused by susceptible orgs. resistant to other drugs. Special Features: Not fused bicyclic. Potent gram-, but limited spectrum (only aerobics and facultative gram-). Little cross-allergenicity w/pen. or ceph. Less toxic than aminoglycs. Usu used in combinations (except for UTIs).

Special Features: Broadest spectrum of all β-lactams. Resistant to penicillinases and most β-lactamases. Resistance develops during treatment.

Name: Methenamine Class: UTI Agent Mech.: Decomposes at pH ≤5.5 to NH4+ and formaldehyde (bactericidal). Absorption: Oral very good, but ↓ pH of stomach decomposes lots of the drug. Enteric-coated tablet solves most of problem. Distribution: Activated 1° in urine. Metab.: NH4+ production requires fxning liver for excretion. Kidneys only important if methenamine mandelate or hippurate is used. Excretion, t_: Excreted in urine. NH4+ reduced requires liver for excretion. Toxicity/S.E.s: GI distress. Long term = rash, hematuria, albuminuria, painful/frequent micturition. Utility: Chronic suppression of UTIs. Special Features: No resistance formation. Orgs which raise urine pH inhibit formaldehyde formation → ↓ sensitivity.

Name: Nitrofurantoin (Furadantin) Class: UTI Agent Mech.: Unclear. Baceria activate nitrofurantoin more rapidly than do mammalian cells. Bacteriostatic in low conc., cidal in high conc. Absorption: Rapidly and completely absorbed after oral admin. Distribution: Antibact. conc. not achieved in plasma. Active in urine. Metab.: Excretion, t_: Toxicity/S.E.s: GI effects, pulm. toxicity (acute pneumoinitis, subacute interstitial pulonary fibrosis), hypersensitivity rxns. chronic hepatitis, neuro efffects. Turns urine brown. Not for preg. women or infants (hemolytic anemia). Not to be mixed w/probenecid. Utility: Uncomplicated lower UTIs caused by E. coli, Enteroccus, prevention of recurrence of UTIs. Special Features: Effect enhanced by urine pH≤5.5.

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Name: Cinoxacin (Cinobac) Class: Nonfluorinated quinolone Mech.: Inhib bact. DNA gyrase (topoisomerase II). Bactericidal. Absorption: Oral Distribution: Metab.: Excretion, t_: Toxicity/S.E.s: Usu. not severe. GI, CNS. Not for pregnant or nursing women or prepubertal children. Utility: UTIs due to coliform bacteria Special Features:

Name: Ciprofloxacin (Cipro) Class: Fluorinated quinolone Mech.: Inhib bact. DNA gyrase (topoisomerase II). Bactericidal. Absorption: Rapid absorption after oral admin. Distribution: Good tissue penetration. Poor CSF. Metab.: Partial hepatic metab. Excretion, t_: Glomerular filtration, secretion. Also feces, bile, sputum. 4 hrs. Toxicity/S.E.s: Usu. not severe. GI, CNS, arthropathy. Not for pregnant or nursing women or prepubertal children. Utility: Upper and lower UTIs, DOC for Pseudomonas UTIs. Active against aerobic gram- bacilli, H. influenzae, Neisseria. Good alternate. for several causes of infectious diarrhea, osteomyelitis, and patients w/CF. Special Features: Broader spectrum than nonfluorinated quinolones.

Name: Norfloxacin (Noroxin) Class: Fluorinated quinolone Mech.: Inhib bact. DNA gyrase (topoisomerase II). Bactericidal. Absorption: Oral admin. Distribution: Good tissue penetration. Metab.: Excretion, t_: Toxicity/S.E.s: Usu. not severe. GI, CNS. Not for pregnant or nursing women or prepubertal children. Utility: UTIs due to Enterobacteriaceae, Enteroccus, Staph, Pseudomonas. Special Features: Broader spectrum than nonfluorinated quinolones.

Name: Phenazopyridine (Pyridium) Class: Analgesic (not an antibiotic) Mech.: Analgesic effect on urinary tract mucosa. Absorption: Distribution: Metab.: Excretion, t_: 90% excreted in urine w/in 24 hrs. Toxicity/S.E.s: GI, headaches. Not for use w/renal insufficiency or severe hepatitis. Hemolytic anemia. Cancer in rats. Stains urine, skin, sclera, and contact lenses red-orange. Utility: Relief of dysuria and urethral irritation assoc. w/acute cystitis, trauma, surgery, catheterization, endoscopy. Special Features: When used w/antibacterial agent, should be discontinued after 48 hr. Should never be used on long-term basis to mask undiagnosed urinary tract pain.

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Name: Streptomycin Class: Aminoglycoside

Name: Neomycin (Mycifradin) Class: Aminoglycoside

Mech.: O2 dependent uptake → inhib. of protein synth by binding to 30S rib. subunit → leaky membranes. Bactericidal.

Mech.: O2 dependent uptake → inhib. of protein synth by binding to 30S rib. subunit → leaky membranes. Bactericidal.

Absorption: Poor oral absorption. Usu. IM or IV. Distribution: Limited to extracellular space. Poor CSF, ocular. No placenta. Excretion, t_: glomerular filtration. 2 hrs. Toxicity/S.E.s: Ototoxicity. Vestibular toxicity. Low nephrotoxicity. Utility: Used in comb. therapy for tuberculosis. Used alone for bubonic plague and tularemia.

Absorption: Very little oral absorption. Topical. Distribution: Limited to extracellular space. Poor CSF, ocular. No placenta. Excretion, t_:

Special Features: Resistance 1° due to plasmid-med. mod. of aminoglyc. Also alter. of transport system, mutation of rib. subunit.

Special Features: Resistance 1° due to plasmid-med. mod. of aminoglyc. Also alter. of transport system, mutation of rib. subunit.

Name: Gentamicin (Garamycin) Class: Aminoglycoside

Name: Tobramycin (Nebcin) Class: Aminoglycoside

Mech.: O2 dependent uptake → inhib. of protein synth by binding to 30S rib. subunit → leaky membranes. Bactericidal.

Mech.: O2 dependent uptake → inhib. of protein synth by binding to 30S rib. subunit → leaky membranes. Bactericidal.

Absorption: Poor oral absorption. Usu. IM or IV. Distribution: Limited to extracellular space. Poor CSF, ocular. No placenta. Excretion, t_: glomerular filtration. 2 hrs. Toxicity/S.E.s: Ototoxicity (aud., vest.), nephtrotoxicity. Utility: Nosocomial aerobic gram- infects, esp. in immunocomp, neutropenics. Often used in synergistic combs to treat P. aeruginosa, enteroccus, lifethreatening gram- sepsis. Used in comb. against S. aureus. Ineffective against anaerobes.

Absorption: Poor oral absorption. Usu. IM or IV. Distribution: Limited to extracellular space. Poor CSF, ocular. No placenta. Excretion, t_: glomerular filtration. 2 hrs. Toxicity/S.E.s: Ototoxicity (aud., vest.), nephtrotoxicity (less than gentamicin). Utility: Nosocomial aerobic gram- infects, esp. in immunocomp, neutropenics. Often used in synergistic combs to treat P. aeruginosa, enteroccus, lifethreatening gram- sepsis. Used in comb. against S. aureus. Ineffective against anaerobes.

Special Features: Resistance 1° due to plasmid-med. mod. of aminoglyc. Also alter. of transport system, mutation of rib. subunit.

Special Features: Resistance 1° due to plasmid-med. mod. of aminoglyc. Also alter. of transport system, mutation of rib. subunit.

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Toxicity/S.E.s: Parenteral → severe ototoxicity and nephrotoxicity. Utility: Topical treatment of superf. sensitive skin and eye infections. Preoperative prophylaxis for bowel surgery.

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Name: Amikacin (Amikin) Class: Aminoglycoside Mech.: O2 dependent uptake → inhib. of protein synth by binding to 30S rib. subunit → leaky membranes. Bactericidal. Absorption: Poor oral absorption. Usu. IM or IV. Distribution: Limited to extracellular space. Poor CSF, ocular. No placenta. Excretion, t_: glomerular filtration. 2 hrs. Toxicity/S.E.s: Ototox.(aud., vest.)(>than gent or tobr), nephtrotox.(
Name: Azithromycin (Zithromax) Class: Macrolide (azalide) Mech.: Inhib protein synth by binding to 50S rib. subunit. Bacteriostatic Absorption: Good oral. Better than erythromycin. Distribution: Good tissue penetration. Better than erythromycin. Metab.: Hepatic metab. Excretion, t_: Bile excretion. 68 hrs. Toxicity/S.E.s: fewer than erythromycin, esp. GI. No interference w/cytochrome p450 metab. Utility: Alternate to pen. in mild-moderate infects (esp. Strep, H. influenzae). DOC for Legionnaire’s disease, Diphtheria carrier state, Mycoplasma pneumoniae infects, Whooping cough (Bordatella pertussis) Special Features: Expanded spectrum over classic macrolides (more potent against gram- bacilli, chlamydiae).

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Name: Erythromycin Class: Macrolide Mech.: Inhib protein synth by binding to 50S rib. subunit. Bacteriostatic Absorption: Orally effective. Enteric-coated tablets. Distribution: Good tissue penetration, but poor CSF. Metab.: Hepatic metab. Excretion, t_: Secreted in bile as active drug. 1.6 hr. Toxicity/S.E.s: GI irritation.,rashes, ototoxicity (large parenteral doses), drug interactions due to inhib of hepatic metab. Utility: Alternate to pen. in mild-moderate infects (esp. Strep, H. influenzae). DOC for Legionnaire’s disease, Diphtheria carrier state, Mycoplasma pneumoniae infects, Whooping cough (Bordatella pertussis) Special Features: Not recommended for severe staph. infections or for meningitis.

Name: Clindamycin (Cleocin) Class: Lincosamide Mech.: Inhib protein synth by binding to 50S rib. subunit. Bacteriostatic. Absorption: Nearly complete oral absorption. IV. Distribution: Good into most tissues, including bone. Poor CSF. Metab.: Hepatic metab. Excretion, t_: Renal excretion. 2.7 hr. Toxicity/S.E.s: High incidence of diarrhea. Antibiotic-assoc. pseudomembranous colitis. Skin rashes. Local thrombophlebitis due to IV. Utility: Alternate to pen. or eryth. in susceptible infections. One DOC for nonCNS anaerobic infections. Used topically for acne. Special Features:

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Name: Vancomycin (Vancocin) Class: Polypeptide Absorption: Poorly absorbed from GI tract. Usu given IV Distribution: Poor CNS Metab.: Excretion, t_: Renal excretion Toxicity/S.E.s: Ototoxicity, nephrotoxicity, thrombophlebitis (IV). In patients w/AIDS, “red man” syndrome (diffuse flushing) Utility: Last ditch measure against severe MRSA infects. DOC for antibiotic assoc. pseudomembranous colitis (oral). Special Features: Narrow spectrum (gram+ cocci), spec. MRSA, C. difficile.

Name: Metronidazole (Flagyl) Class: Nitroimidazole derivative Mech.: Inhib. DNA synth, degrades DNA, e- acceptor for reduced substrates. Absorption: Complete, quick oral absorption. Distribution: Well distrib to all tissues and fluids (including CSF) Metab.: Hepatic metab. Excretion, t_: Toxicity/S.E.s: GI, metallic taste, neurotox (vertigo), disulfiram-like effect w/alcohol, neutropenia. Not for first trimester preg (mutagenic). Not for patients w/active CNS disease or hist. of blood dyscrasias. Utility: IV treatment of anaerobic infects. Oral for amebiasis, giardiasis, and genital infects of Trichomonas vaginalis. Special Features: Antiparasitic and antibacterial activity. All anaerobic cocci and anaerobic gram- bacilli, including Bacteriodes. Trichomonasis, amebiasis, giardiasis.

Name: Acyclovir (Zovirax) Class: Antiviral Mech.: Inhib. DNA synthase (most selective for herpes virus). Phosphorylated by viral thymidine kinase. Then inhib. viral DNA polymerase by competing w/deoxyguanosine triphosphate. Absorption: Distribution:some CSF Metab.: Excretion, t_: Renal secretion, 2.5 hr. Toxicity/S.E.s: Topical admin may cause loal irritation. IV may cause local phlebitis, rash. Encephalophaty in renal-impaired. Utility: Topical, oral, IV application to treat herpes infections. Special Features:

Name: Ganciclovir (Cytovene) Class: Antiviral Mech.: Phosph by viral thymidine kinase. Competes w/normal nucleotides. Prevents chain elongation upon incorporation. Also inhib. viral and cellular DNA polymerase. Absorption: Poor oral. Usu. given IV. Distribution: Good CSF Metab.: Excretion, t_: Renal excretion. 4 hr. Toxicity/S.E.s: Bone marrow suppression. Teratogenic and mutagenic in experimental animals. Utility: Cytomegalovirus Special Features:

Mech.: Blocks peptidoglycan polymerization → inhib cell wall synth. Bactericidal.

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Name: Foscarnet (Foscavir) Class: Antiviral Mech.: Phosph by viral thymidine kinase. Competes w/normal nucleotides. Prevents chain elongation upon incorporation. Also inhib. viral and cellular DNA polymerase. Absorption: Poor oral. Usu. given IV. Distribution: Good CSF Metab.: Excretion, t_: Renal excretion. 4 hr. Toxicity/S.E.s: Renal dysfxn #1. Nausea, vomiting, headache, fatigue, anemia. Utility: Cytomegalovirus Special Features: 3x more expensive than gancyclovir.

Name: Trifluridine (Viroptic) Class: Antiviral Mech.: Pyrimidine analog. Competes with TTP for incorp into viral DNA. Inhib. viral DNA synth. Absorption: Distribution: 1% soln applied to cornea. Not given systemically Metab.: Excretion, t_: Toxicity/S.E.s: Mutagenic and teratogenic activity in experimental tests. Utility: Topical treatment for keratoconjunctivitis. Special Features:

Name: Interferon alpha 2b (Intron A) Class: Antiviral Mech.: Bind to cell-surface receptors and inhibit viral penetration or uncoating, synth or methylation of mRNA, translation of viral proteins, viral assembly or release, and degrade mRNA. → Inhib. viral protein synth. Also induce a protein kinase that inactivates protein eIF-2 which is necessarty for protein synth initiation. Absorption: Low oral activity. Usu. given IM or SC Distribution: Metab.: Rapid degradation. Excretion, t_: 40 min. Toxicity/S.E.s: influenza-like illness. Bone marrow suppression w/granulocytopenia and thrombocytopenia. Antibodies develop w/continued use. Continued nasal admin → mucosal damage.

Name: Amantadine (Symmetrel) Class: Antiviral/Antiparkinsonian Agent Mech.: Blocks a late stage in assembly of influenza A virus Absorption: Well absorbed orally. Distribution: Metab.: Excretion, t_: Excreted unchanged in urine. Toxicity/S.E.s: CNS toxicity (nervousness, confusion, hallucinations, insomnia, depression, confusion). Overdose → toxic psychosis. Freq. livedo reticularis (skin mottling). Peripheral edema, freq. nausea. C/I w/hist. of seizures or congestive heart failure. Amantadine>rimantadine

Utility: Treat hepatitis B and C

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Utility: Treat influenza A. Treat Parkinson’s Disease symptoms → improvement o akinesia, rigidity, tremor, gait disturbances, & total disability in ~ 50% of patients (mech. unknown). Use alone or w/L-Dopa for PD. Features: Can be used prophylactically for influenza A. For PD, sustained improvement may last up to 30 months, but may also be short lived (1-3 months). For PD, as good as or better than anticholinergics.

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Name: Rimantadine (Flumadine) Class: Antiviral Mech.: Blocks a late stage in assembly of influenza A virus Absorption: Well absorbed orally. Distribution: Metab.: Hepatic metab. Excretion, t_: Toxicity/S.E.s: CNS toxicity (nervousness, confusion, hallucinations, insomnia) amantadine>rimantadine Utility: Treat influenza A Special Features: Can be used prophylactically.

Name: Ribavirin (Virazole) Class: Antiviral Mech.: Purine analog. After phosphorylation, inhibits enzymes involved in guanine nucleotide synth. After further phosph, inhib several viralspecific enzymes involved in DNA synth. Absorption: Oral bioavail 45%. IV. Aerosol. Distribution: Metab.: Excretion, t_: 40 days

Name: Azidothymidine (Zidovudine, AZT) Class: Antiviral Mech: Thymidine analog. After phosph, inhib. viral RNA-dependent DNA polymerase (reverse transcriptase). Causes chain termination after incorporation. Absorption: Oral bioavail 60-65%. Distribution: good CSF Metab.: Metab. to glucuronide. Antag. by ribavirin Excretion, t_: 1 hr. Toxicity/S.E.s: Granulocytopenia (45%), anemia (transfusions necessary 30%), headache, nausea, insomnia, myalgia. Utility: Treatment of HIV. Decreases plasma HIV RNA, increases CD4 cells, decreases # of opportunistic infects, prolongs survival. Reduces risk of transmission by pregnant women to fetuses from 28% to 8%. Special Features:

Name: Dideoxyinosine (Didanosine, Videx, DDI) Class: Antiviral Mech.: Inhib reverse transcriptase. Absorption: Distribution: Metab.: Excretion, t_: Toxicity/S.E.s: Peripheral neuropathy, rash, stomatitis, esophageal ulceration, pancreatitis, fever. Utility: Treat HIV. Strains resistant to AZT may be susceptible. After treatment, may become susceptible again to AZT. Alternating treatment superior to either alone. Special Features:

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Toxicity/S.E.s: Accumulates in erythrocytes → hemolytic anemia. Bone marrow suppression. GI, CNS aggravation. Teratogenic and mutagenic in animals. Toxicity avoided w/aerosol admin (for RSV). Antagonizes AZT activity. Utility: Aerosol form used to treat respiratory syncytial virus. Most important drug for treatment of hemorrhagic fever. Special Features:

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Name: Dideoxycytosine (Zalcitabine, Hivid, DDC)) Class: Antiviral Mech.: Inhib reverse transcriptase. Absorption: Distribution: Metab.: Excretion, t_: Toxicity/S.E.s: Peripheral neuropathy, rash, stomatitis, esophageal ulceration, pancreatitis, fever. Utility: Treat HIV. Strains resistant to AZT may be susceptible. After treatment, may become susceptible again to AZT. Alternating treatment superior to either alone. Special Features:

Name: Indinavir (Crixivan) Class: Antiviral Mech.: Inhib HIV protease activity Absorption: Oral Distribution: Metab.: Excretion, t_: Toxicity/S.E.s: Utility: Treat HIV Special Features: Active against strains resistant to reverse transcriptase inhibitors.

Name: Ritonavir (Norvir) Class: Antiviral Mech.: Inhib HIV protease activity Absorption: Oral Distribution: Metab.: Excretion, t_: Toxicity/S.E.s: Utility: Treat HIV Special Features: Active against strains resistant to reverse transcriptase inhibitors.

Name: Saquinavir (Invirase) Class: Antiviral Mech.: Inhib HIV protease activity Absorption: Oral Distribution: Metab.: Excretion, t_: Toxicity/S.E.s: Utility: Treat HIV Special Features: Active against strains resistant to reverse transcriptase inhibitors.

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Name: Isoniazid (INH) Class: Antitubercular Mech.: Tuberculostatic to resting bacilli, tuberculocidal to rapidly dividing cells. Enters cells via active uptake. Interferes w/DNA synth, glycolyis, synth of mycolic acid (unique component of mycobacteria) Absorption: Rapidly absorbed after oral admin. Distribution: Distributes in total body water. Retained in infected tissue. Metab.: Acetylated in liver. Excretion, t_: Urine. 75-90% in urine as metabolites in 24 hrs. Toxicity/S.E.s: Direct—inactivation/depletion of pyridoxine → peripheral neuritis (treat prophylactically w/supplemental pyridoxine). Hypersensitivity rxns. Hepatitis (can be fatal) due to toxic metabolites. Convulsions, optic neuritis, toxic encephalopathy, reversible psychotic episodes. Utility: Most important and widely used drug for tuberculosis. Prob. w/resistance. Special Features: Only drug approved for prophylaxis of tuberculosis.

Name: Ethambutol (Myambutol) Class: Antitubercular Mech.: Tuberculostatic, mech. unknown, may involve inhib of mycolic acid synth. Absorption: Well absorbed orally. Not affected by food. Distribution: Metab.: Excretion, t_: Renal excretion (50% unchanged and 15% inactive metab. in 24 hr) Toxicity/S.E.s: Few. Decreased visual acuity and ability to perceive color green (usually reversible). Gout. Utility: Treat TB. Resistance develops is used alone. Usu. used with isoniazid. Special Features:

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Name: Rifampin (Rifadin) Class: Antitubercular Mech.: Inhib. of bact. DNA-dependent RNA polymerase. Resist develops rapidly. Absorption: Orally effective Distribution: Diffuses freely into tissues and fluids Metab.: Liver Excretion, t_: 30% excreted in urine (50% active). T1/2= 1.5-5 hrs. ↓ in slow acetylaters. Toxicity/S.E.s: Low incidence. Jaundice (can be fatal). Use w/caution w/impaired liver fxn. Induces hepatic microsomal enzymes. GI distress, diarrhea, CNS complaints, hypersensitivity. Influenzalike syndrome. Utility: Rapidly improves TB patients to non-infectious state. Always used w/other agents. Esp. useful in serious cases of TB. Asymptomatic carriers of N. meningitis, eryth-resist. Legionella pneumophila infects. DOC for prophylaxis of H. influenza meningitis.

Name: Pyrazinamide Class: Antitubercular Mech.: Bactericidal. Unknown mech. Absorption: Well absorbed orally. Not affected by food. Distribution: Dist. in total body water. Metab.: Partially metabolized — hydrolyzed, hydroxylated Excretion, t_: Glomerular filtration. 8 hrs. Toxicity/S.E.s: Liver necrosis, hyperuricemia, nausea, vomiting, complication of diabetes management. Utility: Used to treat TB when there is resistance to other agents. Requires 3 additional effective agents. Special Features:

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Name: Amphotericin B (Fungizone) Class: Antifungal (Polyene) Mech.: Assoc. w/ergosterol in fungal membrane → 4-5 Å pores. Fungistatic at low conc. Fungicidal at high conc. Absorption: Insoluble in water. Colloidal preparation injected IV. Not absorbed orally, IM, or after bladder irrigation. Used topically. Distribution: Bound to cholesterol and lipoprotiens. Poor CSF. Intrathecal may be necessary to treat meningitis. Excretion, t_: Excreted very slowly as inactive metabolite by kidney. Toxicity/S.E.s: Nephrotoxicity (80%) requires hospitalization for administration. Chills (50%), fever, nausea, vomiting, diarrhea, headache, phlebitis, suppression of RBC synth. IT → headache, radiculitis, paresis, paresthesias, visual impairment. Utility: 1° drug used against serious systemic infections. DOC for 1° amebic meningoencephalitis caused by Naegleria. Alt. for American cutaneous or mucocutaneous leishmoniasis. Weekly injections for chronic suppression of Histoplasmosis in AIDS patients. Special Features: No problem w/resistance development. Increases fungal permeability to other agents.

Name: Nystatin Class: Antifungal (Polyene)

Name: Flucytosine (Ancobon) Class: Antifungal Mech.: Converted to 5-fluorouracil in fungi (enzyme not in humans). 5-fluorouracil → phosph deoxyribose that inhibits thymidylate synth. Fungistatic. Absorption: Well absorbed orally. Distribution: Passes BBB (75%) → good CSF. Aqueous humor, bronchial secretions. Poorly bound by serum proteins. Metab.: Excretion, t_: 1° glomerular filtration (unmetab. product). 3-4 hr → 200 hr w/renal failure. Dose must be adjusted if renal fxn compromised. Toxicity/S.E.s: Bone marrow depression with anemia, thrombocytopenia, leukopenia. Nausea, rashes, eosinophilisa, severe diarrhea, reversible hepatic dysfxn. Confusion, hallucinations, headache, vertigo, possibly fatal enterocolitis (esp. in comb. w/Amphoter.). Utility: DOC for Chromomycosis. Used in comb. w/Amph for systemic Candida Albicans. Special Features: Narrower spectrum than Amphotericin B. Resistance develops rapidly, so usu. used in comb., except to treat Chromomycosis

Name: Ketoconazole (Nizoral) Class: Antifungal (Imidazole) Mech.: Interferes w/ergosterol synth → altered fungal membrane permeability. Absorption: Absorbed well from GI if contents are sufficiently acidic. Distribution: Poor CSF at recommended doses. Ok CSF w/high doses. Metab.: Degraded by liver. Excretion, t_: Excreted mostly into bile. Only 10-15% appears unchanged in urine. Excreted in milk. Toxicity/S.E.s: Fewer than Amphoter. or flucytosine. Rare fatal hepatic necrosis. Dose-dependent decrease in testosterone. Toxicities for nursing infants. Rare anaphylactic shock. Can’t be used w/astemizole, terfenadine, loratadine due to inhib. of metabolism. Coadmin. w/ketoconazole → ↑ conc. of cyclosporin. Increases anticoag. response of anticoag drugs. Coadmin w/isoniazid or rifampin → ↓ ketoconazole. Utility: DOC for Pseudoallescheria boydii. Alternate for C. albicans, H. capsulatum, B. dermatidis, Paracoccidiodes, C. immitis. Special Features: Very broad spectrum. Being phased out and replaced with itraconazole and fluconazole.

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Mech.: Assoc. w/ergosterol in fungal membrane → 4-5 Å pores. Fungistatic at low conc. Fungicidal at high conc. Absorption: Poor oral absorption. Topical admin. Distribution: Metab.: Excretion, t_: Toxicity/S.E.s: No side effects when topically applied Utility: Superficial candidiasis (GI, cutaneous, oropharyngeal, vulvovaginal) via topical, oral, or vaginal admin. Special Features: Safe during pregnancy.

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Name: Itraconazole (Sporanox) Class: Antifungal (Triazole) Mech.: Inhib. cytochrome P450-dependent synth of ergosterol. Absorption: Oral absorption good. Better in presence of food, high gastric acidity. Distribution: Neglibible CSF, saliva. Metab.: Extensively metab. in liver. Excretion, t_: Very little active drug remains in urine. Toxicity/S.E.s: Nausea, vomiting, headache, rash, loss of libido, impotence, gynecomastia. Rare hepatotoxicity. Inhib. metab. of long-acting antihistamines (sim. to ketoconazole), erythromycin, triazolam, cisapride. Utility: DOC for many superficial and systemic infections. Alternate for many superf. and systemic infections. Oral treatment of onychomycoses. Same indications as ketocon., but also active against lymphocutaneous form of sporotrichosis plus Aspergillosis. Usu. preferred to ketoconazole. Special Features:

Name: Fluconazole (Diflucan) Class: Antifungal (Triazole) Mech.: Inhib. fungal cyt. P450 and sterol C-14 α-demethylation. Normal sterols depleted, 14-α-methyl sterols build up → fungistatic. Absorption: Oral absorption ≅ IV absorption (rare phenom.) Distribution: Low plasma protein binding. Vd close to total body water. Good saliva, good CSF (~80%), conc. in urine and skin. Metab.: Excretion, t_: 80% appears in urine unchanged. Excreted in milk. 30 hr. Toxicity/S.E.s: Rare hepatotoxicity. Rare exfoliative skin disorders (can be fatal). GI irritation, rash. Affects rat fetal development. Increases metabolite levels of some terfenadine metabolits (not terf. itself). May slow metab. of long-acting antihistamines and cyclosporines. Utility: Candidiasis (oropharyngeal, esophageal, UTI, vaginal, systemic), Cryptococcal meningitis in AIDS patients and otherwise healthy patients. Coccidiodal meningitis. Chronic suppresion of Crypt. meningitis in AIDS patients. Single-dose therapy for vaginal yeast infections. Special Features: Oral absorption ≅ IV absorption. Only causes minor changes in plasma testosterone and corticosteroid concentrations.

Name: Griseofulvin (Grifulvin) Class: Antifungal Mech.: Binds to microtubules, disrupts mitotic spindle, blocks mitosis. Fungistatic.

Name: Miconazole (Monistat, OTC=Micatin) Class: Antifungal (Imidazole) Mech.: Causes leakage of small molecules/ions across plasma membrane. Also blocks purine uptake. Fungistatic at low conc. Fungicidal at high conc. Absorption: Good oral, but not admin due to GI irritation. Topical, IV, IT. Distribution: Good CSF

Absorption: Always given orally. Erratically absorbed. Fatty meals → ↑ absorption. Distribution: Binds in high conc. to keratin in areas of skin, hair, nails most affected by dermatophytes. Metab.: Toxicity/S.E.s: Headache, rare CNS effects (memory lapse, impaired judgment, blurred vision. Candida superinfection. High doses carcinogenic, teratogenic. Disulfiram-like effect with alcohol. Reduces efficacy of some oral contraceptives. Utility: Inhibits most dermatophytes and superfic. yeast infections. Treats most types of tinea, ringworm, athletes foot. Special Features: Cures at the base of the problem. When the cured base grow completely out, patient is cured. Long eradication time. Poor cure rate.

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Toxicity/S.E.s: Topical → occasional burning and irritation. IV/IT may cause cardiorespiratory failure, thrombophlebitis. Utility: Topical against common fungal infections of skin and vagina. Better than nystatin for vaginal candidiasis. Esp. useful in mixed skin infections featuring dermatophytes and Candida. Best topical agent for dermatophytoses (even severe). Efficacy = 90%. IV/IT as alternative for systemic Pseudallescheriasis infection (only non-topical use). Special Features: Safe during pregnancy. Broad spectrum against fungi. Also active against gram+ bacteria.

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Name: Clortrimazole (Lotrimin) Class: Antifungal (Imidazole) (OTC) Mech.: Causes leakage of small molecules/ions across plasma membrane. Also blocks purine uptake. Fungistatic at low conc. Fungicidal at high conc. Absorption: Good oral, but not admin due to GI irritation. Topical. Distribution: Good CSF Toxicity/S.E.s: Topical → occasional burning and irritation. Utility: Topical against common fungal infections of skin and vagina. Better than nystatin for vaginal candidiasis. Esp. useful in mixed skin infections featuring dermatophytes and Candida. Good topical agent for dermatophytoses. Troches esp. recommended for oropharyngeal candidiasis. Special Features: Safe during pregnancy. Broad spectrum against fungi. Also active against gram+ bacteria. At high conc, also trichomonocidal.

Name: Tolnaftate (Aftate, Tinactin) Class: Antifungal (OTC) Mech.: Absorption: Distribution: Metab.: Excretion, t_: Toxicity/S.E.s: Utility: 80% efficacy against dermatophytes Special Features:

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Name: Ciclopirox (Loprox) Class: Antifungal (OTC) Mech.: Absorption: Penetrates dermis, hair follicles, sebaceous glands. Distribution: Metab.: Excretion, t_: Toxicity/S.E.s: Utility: 81-94% cure rate for cutaneous candidiasis, tinea corporis, tinea pedis, versicolor. May (one report) be useful in topical treatment of onychomycosis. Special Features:

Name: Undecylenic Acid (Desenex) Class: Antifungal (OTC) Mech.: Absorption: Distribution: Metab.: Excretion, t_: Toxicity/S.E.s: Utility: <50% efficacy against athlete’s foot Special Features:

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Name: Iodide Class: Antifungal? Halide? Mech.: Absorption: Distribution: Metab.: Excretion, t_: Toxicity/S.E.s: Utility: Used as alternate treatment for superficial cutaneous Sporotrichosis. Special Features:

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Name: Digoxin (Lanoxin) Class: CHF Rx (Cardiac Glycoside)

Name: Digitoxin (Crystodigin) Class: CHF Rx (Cardiac Glycoside)

Mech.: Inhib. of Na+ /K+ ATPase → ↑ release of Ca2+ from SR → ↑ myocardial contractility. Also ↑ sensitivity of AV node to vagal stimulation → ↓ ventricular rate in atrial flutter or fibrillation (i.e., anti-arrhythmic). Absorption: Dist.: Metab.: Very little. Excretion, t_: Urine. Short t_. Toxicity/S.E.s: Low therapeutic index. Toxicity enhanced by hypokalemia. Arrhythmias (possibly life-threatening), anorexia, n/v/d, drowsiness, fatigue, visual disturbances. Verapamil or quinidine → ↑ toxicity.

Mech.: Inhib. of Na+ /K+ ATPase → ↑ release of Ca2+ from SR → ↑ myocardial contractility. Also ↑ sensitivity of AV node to vagal stimulation → ↓ ventricular rate in atrial flutter or fibrillation (i.e., anti-arrhythmic). Absorption: Dist.: Strong protein binding. Metab.: Hepatic metab. Excretion, t_: Feces. Longer t_ than digoxin. Toxicity/S.E.s: Low therapeutic index. Toxicity enhanced by hypokalemia. Arrhythmias (possibly life-threatening), anorexia, n/v/d, drowsiness, fatigue, visual disturbances. Verapamil or quinidine → ↑ toxicity.

Utility: Treat heart failure. DOC for atrial fibrillation/flutter. Special Features: No active metabolites. Shorter t_, less GI absorption, and less protein binding than digitoxin. Only cardiac glycoside routinely used.

Utility: Treat heart failure. Special Features: Active metabolites. Longer t_, more GI absorption, and more protein binding than digoxin.

Name: Dobutamine (Dobutrex)

Name: Dopamine Class: CHF Rx (β-Adrenergic Agonist) Mech.: ↓ dose → D1 stim. ↑ dose → β1 stim. Also releases NE from symp. neur. Causes

Class: CHF Rx (Mixed (α-β) Agonist (Cardioselective)) Mech.: Stim. α and β receptors, but not DA. → ↑ CO w/o ↑ HR. ↑ stroke volume. No/little change in peripheral resistance. ↑ cAMP → ↑ contractility. Absorption: IV → rapid onset (1-2 min). Peak effect ~ 10 min. Dist.: Metab.: Methylation by COMT. Conjugation Excretion, t_: 2 min. Toxicity/S.E.s: ↑ BP, ↑ HR, tachycardia, ventricular ectopic activity. ↑ myocard. O2 consump. may cause ↑ size MI. Tachyphylaxis to β stim. Utility: Short-term treatment of cardiac decompensation after cardiac surgery or w/CHF or acute MI. Often DOC after acute MI. Treatment of shock after correction of hypovolemia.

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vasodilation in renal, mesenteric, and coronary beds → ↑ renal blood flow, glomerular filtration, and Na+ excretion. Also causes ↓ Na+ and H20 resorption. High doses → ↑ HR. Usu. increases systolic BP and pulse pressure. Low-mod. doses → static or decreased vasc. resistance. High conc. → α1 activation → vasoconstriction → ↑ BP. ↑ cAMP → ↑ contractility.

Absorption: No oral. IV. Onset w/in 5 min. Dist.: Metab.: Catab. by COMT and MAO, esp. in liver and kidneys. Glucuronidation and sulfconjugation Excretion, t_: Duration of action 10 min. t_: 2 min. Toxicity/S.E.s: Nausea, vomiting, tachycardia, anginal pain, arrhythmia, headache, hypertension, vasoconstriction. Usu. due to excessive symp activity. Treat by stopping admin. or w/α blockers. Local ischemic necrosis. Contraind. w/pheochromocytomas, uncorrected tachyarrhythm. or vent. fibrillation, MAO inhibitors, furazolidone. Adjust dose w/tricyclics. Utility: Some shock (e.g., oliguria and low-normal periph. resist, cardiogenic/septic shock). CHF.

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Name: Amrinone (Inocor) Class: CHF Rx (PDE Inhibitor)

Name: Hydralazine Class: CHF Rx (Vasodilator)

Mech.: Inhib. of PDE III→ ↑ cAMP → ↑ contractility, ↑ stroke volume, ↑ ejection fraction, ↑ heart rate, ↑ exercise capacity. In smooth muscle, inhib. → vasodilation.

Mech.: Acts directly on smooth muscle cells → vasodilation. Mech. unknown. ↓ BP → reflex tachycardia & ↑ CO. ↑ renin concentration. ↑ NE in heart failure. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Reversible lupus-like synd. Headache, nausea, sweating, arrhythmia, angina, tachycardia.

Absorption: IV only. Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: ↑ mortality from heart failure (possibly due to arrhythmogenesis). Utility: Treat CHF. Special Features:

Utility: Treat CHF. Chronic use → reduction in two year mortality by 34%. Almost always coadmin. w/β-blocker (to oppose tachycardia) and a diuretic (to decrease Na+ retention). Treat resistant HTN and hypertensive emergencies. Special Features:

Name: Diazoxide (Hyperstat I.V.) Class: CHF Rx (Vasodilator) (Antihypertensive)

Name: Minoxidil (Loniten) Class: CHF Rx (Vasodilator) (Antihypertensive)

Mech.: Direct arteriolar vasodilation → ↓ TPR → reflex ↑ in HR & CO.

Mech.: Direct arteriolar vasodilation → ↓ TPR → reflex ↑ in HR & CO.

Absorption: IV. Dist.: Metab.: Excretion, t_: Long duration of action. Toxicity/S.E.s: Severe tachycardia, prolonged hypotension (possibly resulting in stroke or MI). Utility: Treat hypertensive emergencies, hypertensive encephalopathy, and eclampsia. Special Features:

Absorption: Oral. Dist.: Metab.: Excretion, t_:

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Toxicity/S.E.s: Severe tachycardia. Serious Na+ & H2O retention → volume overload, edema, CHF. Hypertrichosis. Utility: Treat severe-malignant HTN refractory to other drugs. Male pattern baldness. Special Features: Reflex tachycardia may be severe, requiring concomitant use of a diuretic and a β-blocker.

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Name: Nitroprusside (Nipride) Class: Antihypertensive Agent Mech.: Stim. membrane-assoc. guanylyl cyclase in vascular smooth muscle cells → ↑ intracellular cGMP → activation of cGMP-dependent protein → vasodilation of arterial and venous vessels→ reflex tachycardia. Reduces BP in all pts., regardless of etiology. Decreases afterload and preload. Absorption: Continuous IV infusion. Oral → cyanide poisoning. Dist.: Metab.: Excretion, t_: Minutes Toxicity/S.E.s: Tachycardia, hypotension, cyanide toxicity (Rx w/sodium thiosulfate). Utility: Hypertensive emergencies. Special Features:

Name: Nifedipine (Procardia) Class: Calcium-Entry Blocking Agent (Dihydropyridine) Mech.: Binds to L-type Ca2+ channels → ↓ Ca2+ in arterial smooth muscle cells → vasodilation → ↓ TPR, ↑ coronary blood flow, ↓ cardiac afterload. Little/no effect on venous vessels. No direct effect on conduction or automaticity. Vasodilation → reflex ↑ sympathetic response → ↑ HR, ↑ contractility. Net = ↓ BP, ↑ HR, ↑ contractility, ↑ CO. May inhib. platelet aggreg. Absorption: Oral → nearly complete absorption. 1st pass metab→↓ bioavail. IV. Dist.: Significant protein binding. Metab.: Hepatic. Inducible metab. Inactive metabolites. Excretion, t_: 1.5-6 hr. Repeated oral dose → ↑ t_ due to hepatic saturation. Longer t_ in elderly or pts w/hepatic cirrhosis or renal insuff. Toxicity/S.E.s: Dizziness, hypotension, headache, flushing, peripheral edema, gingival hyperplasia. Aggravation of myocardial ischemia, angina. C/i w/CHF. Utility: Rx angina (stable, variant, unstable), arrhythmias, hypertension. DOC for stable angina w/persistent HTN, sinus bradycardia, or AV node dysfxn. W/β-blocker & nitrate → ↓ rest angina, ↓ risk of MI, ↓ risk of emergency revascularization. Special Features:

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Name: Verapamil (Calan) Class: Calcium-Entry Blocking Agent (Antidysrhythmic Agent Class IV) Mech.: Binds to L-type Ca2+ channels → ↓ Ca2+ in arterial smooth muscle cells → vasodilation → ↓ cardiac afterload. Little/no effect on venous vessels. ↓ inotropy, chronotropy, & dromotropy. Net = ↓ HR, ↓ conduction, ↓ contractility, ↓ BP. May inhib. platelet aggreg. Absorption: Oral → nearly complete absorption. 1st pass metab→↓ bioavail. IV. Dist.: Significant protein binding. Metab.: Hepatic. Inducible metab. Inhibits hepatic enzymes. Active metabolites. Excretion, t_: 1.5-6 hr. Repeated oral dose → ↑ t_ due to hepatic saturation. Longer t_ in elderly or pts w/hepatic cirrhosis or renal insuff. Toxicity/S.E.s: Dizziness, hypotension, headache, constipation, gingival hyperplasia, flushing, edema. Aggravation of myocardial ischemia (less than w/DHPs). Serious toxicities (bradycardia, transient asystole, exacerbation of heart failure) are rare, but may occur after IV admin; coadmin w/β-blocker (c/i); or in pts. w/ventricular dysfxn, conduction disturbances, or systolic BP < 90 mm Hg (c/i). ↑ digoxin levels. C/i w/CHF, quinidine. Utility: Rx angina (stable, variant, unstable), arrhythmias, hypertension. More effective than propranolol for unstable angina. DOC (IV) for paroxysmal supraventricular tachycardias. Reentry arrhythmias. Special Features: Blocking action is frequency and voltage dependent. ∴ more effective in rapidly depolarizing cells. At vasodilatory doses, greater negative chronotropic, dromotropic, and inotropic effects than the dihydropyridines. Greatest effect on heart of channel blockers.

Name: Diltiazem (Cardizem) Class: Calcium-Entry Blocking Agent (Antidysrhythmic Agent Class IV) Mech.: Binds L-type Ca2+ channels→ ↓ Ca2+ in arterial smooth muscle cells → vasodilation → ↓ TPR, ↑ coronary blood flow, ↓ cardiac afterload. Little/no effect on venous vessels. ↓ inotropy, chronotropy, & dromotropy. Net = ↓ HR, ↓ contractility, ↓ BP. May inhib. platelet aggreg. Absorption: Oral → nearly complete absorption. 1st pass metab→↓ bioavail. IV. Dist.: Significant protein binding. Metab.: Hepatic. Inducible metab. Inhib. hepatic enzymes. Active metabolites. Excretion, t_: 1.5-6 hr. Repeated oral dose → ↑ t_ due to hepatic saturation. Longer t_ in elderly or pts w/hepatic cirrhosis or renal insuff. Toxicity/S.E.s: Dizziness, hypotension, headache, flushing, edema, constipation (less than verapamil), bradycardia, gingival hyperplasia. Aggravation of myocardial ischemia (less than w/DHPs). ↑ digoxin levels. C/i for pts. w/systolic BP<90 mm Hg or w/conduction disturbances. C/i w/CHF, β-blockers, quinidine. Utility: Rx angina (stable, variant, unstable). Supraventricular tachycardia, reentry arrhyth.. Special Features: Blocking action is frequency and voltage dependent. ∴ more effective in rapidly depolarizing cells. Hemodynamic effects between those of dihydropyridines and verapamil.

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Name: Bepridil (Vascor) Class: Calcium-Entry Blocking Agent (Antidysrhythmic Agent Class IV) Mech.: Binds to L-type Ca2+ channels → ↓ Ca2+ in arterial smooth muscle cells → vasodilation → ↓ TPR, ↑ coronary blood flow, ↓ cardiac afterload. Little/no effect on venous vessels. ↓ inotropy, chronotropy, & dromotropy. Blocks cardiac Na+ /K+ channel. May inhib. platelet. aggreg. Absorption: Oral → nearly complete absorption. 1st pass metab→↓ bioavail. IV. Dist.: Significant protein binding. Metab.: Hepatic. Excretion, t_: Long (24-50 hr.). Repeated oral dose → ↑ t_ due to hepatic saturation. Longer t_ in elderly or pts w/hepatic cirrhosis or renal insuff. Toxicity/S.E.s: 2° to vasodilation—dizziness, hypotension, headache, flushing, edema. Aggravation of myocardial ischemia. Drug-induced long QT syndrome (DILQT, “torsades de pointes”). C/i w/CHF, β-blockers. Utility: Rx angina (stable, variant, unstable), supraventricular tachycardia, reentry arrhythmias, hypertension. Special Features:

Name: Nimodipine (Nimotop) Class: Calcium-Entry Blocking Agent (Dihydropyridine) Mech.: Binds to L-type Ca2+ channels → ↓ Ca2+ in arterial smooth muscle cells → vasodilation → ↓ TPR, ↑ coronary blood flow, ↓ cardiac afterload. Little/no effect on venous vessels. No direct effect on conduction or automaticity. Vasodilation → reflex ↑ sympathetic response → ↑ HR, ↑ contractility. Net = ↓ BP, ↑ HR, ↑ contractility, ↑ CO. May inhib. platelet aggreg. Absorption: Oral → nearly complete absorption. 1st pass metab→↓ bioavail. IV. Dist.: Significant protein binding. Metab.: Hepatic. Inactive metabolites. Excretion, t_: 1.5-6 hr. Repeated oral dose → ↑ t_ due to hepatic saturation. Longer t_ in elderly or pts w/hepatic cirrhosis or renal insuff. Toxicity/S.E.s: 2° to vasodilation—dizziness, hypotension, headache, flushing, edema. Aggravation of myocardial ischemia, angina. C/i w/CHF. Utility: Rx angina (stable, variant, unstable). DOC for stable angina w/persistent HTN, sinus bradycardia, or AV node dysfxn. Special Features:

Name: Hydrochlorothiazide (Hydrodiuril) Class: Diuretic (Thiazide) Mech.: Inhib. Na+ & Cl- transport in the cortical thick ascending limb and the early distal tubule → ↑ NaCl and water excretion & ↓ excretion of Ca2+ and uric acid. Absorption: Oral → good absorption. Takes effect in 1 hr. Dist.: Metab.: Excretion, t_: Short duration of action. Toxicity/S.E.s: Hypokalemia, hyponatremia, hyperuricemia, weakness, hypercalcemia, metabolic alkalosis, postural hypotension, hypercholesterolemia, hypertriglyceridemia, hyperglycemia (in patients w/DM), and rare hypersensitivity rxns. C/i—pts susceptible to problems with hypokalemia (cirrhosis, pts on digitalis), hyperuricemia (gout), or hypercalcemia. Adverse rxns w/digitalis, lithium. Altered doses of anti-diabetic agents required. Long-term NSAID use may decrease anti-HTN effects. Utility: Treat hypertension, CHF, nephrotic synd., other Na+ -retaining states. Reduce Ca2+ excretion (e.g., prevention of kidney stones). Special Features: Most commonly prescribed class of diuretics. Most frequently used class of anti-HTN agents. Milder diuretic action than loop diuretics. Rel. ineffective in renal insuff.

Name: Chlorthalidone (Hygroton) Class: Diuretic (Thiazide) Mech.: Inhib. Na+ & Cl- transport in the cortical thick ascending limb and the early distal tubule → ↑ NaCl and water excretion & ↓ excretion of Ca2+ and uric acid. Absorption: Oral → good absorption. Takes effect in 1 hr. Dist.: Metab.: Excretion, t_: Long duration of action. Toxicity/S.E.s: Hypokalemia, hyponatremia, hyperuricemia, weakness, hypercalcemia, metabolic alkalosis, postural hypotension, hypercholesterolemia, hypertriglyceridemia, hyperglycemia (in patients w/DM), and rare hypersensitivity rxns. C/i—pts susceptible to problems with hypokalemia (cirrhosis, pts on digitalis), hyperuricemia (gout), or hypercalcemia. Adverse rxns w/digitalis, lithium. Altered doses of anti-diabetic agents required. Long-term NSAID use may decrease anti-HTN effects. Utility: Treat hypertension, CHF, nephrotic synd., other Na+ -retaining states. Reduce Ca2+ excretion (e.g., prevention of kidney stones). Special Features: Most commonly prescribed class of diuretics. Most frequently used class of anti-HTN agents. Milder diuretic action than loop diuretics. Rel. ineffective in renal insuff.

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Name: Furosemide (Lasix) Class: Diuretic (Loop Diuretic) Mech.: Blocks the Na+/K+/Cl- co-transporter in the apical membrane of the thick ascending limb of Henle’s loop → ↑ excretion of urinary water, Na+, K+, Ca2+, & Mg2+. Also causes venous and renal vasodilation. Absorption: Oral, IV. Takes effect in 20 min. Dist.: Metab.: Excretion, t_: 1-1.5 hr. Shorter duration than thiazides. Toxicity/S.E.s: Hypokalemia (esp. dangerous if pt. is on digitalis), Ca2+ & Mg2+ depletion, metabolic alkalosis, volume contraction, mild hyperglycemia, thiazide-like lipid changes, sulfonamide allergy cross-rxn, ototoxicity. C/i—pts. susceptible to volume contraction from excessive diuresis (e.g., elderly), and pts. susceptible to problems w/hypokalemia (e.g., cirrhosis, digitalis). Adverse rxn w/lithium, aminoglycosides. Altered doses of anti-diabetic agents required. Utility: Diuresis for hypertension when a short-acting diuretic is indicated. Treat HTN refractory to thiazides. Very useful in conditions refractory to less potent diuretics (e.g., CHF, renal insufficiency, nephrotic synd.). Treat hypercalcemia. Special Features: Most potent diuretics available. Can cause excretion of up to 20% of filtered Na+.

Name: Triamterene (Dyrenium) Class: Diuretic (Potassium Sparing Diuretic) Mech.: Inhib. Na+ channel in the apical membrane of the late distal tubule and collecting duct → block of electrochemical gradient that drives K+ & H+ secretion → diuresis & ↓ excretion of K+ & H+ . Weak anti-HTN activity. Absorption: Oral Dist.: Metab.: Excretion, t_: 1° = kidney. 3 hr. Toxicity/S.E.s: Hyperkalemia (most severe), n/v (most common), metabolic acidosis. Hyponatremia may occur in old folks. Absolutely contraindicated with hyperkalemia. Adverse rxns w/lithium, ACE inhibitors. Rare renal failure w/NSAIDs. Utility: Usu. given w/another diuretic (often thiazide or loop). Combination usu. → normal K+ excretion. Used to prevent or correct hypokalemia, and to avoid K+ depletion in pts. on digitalis. Special Features: Rel. weak diuretic.

Name: Amiloride (Midamor) Class: Diuretic (Potassium Sparing Diuretic) Mech.: Inhib. Na+ channel in the apical membrane of the late distal tubule and collecting duct → block of electrochemical gradient that drives K+ & H+ secretion → diuresis & ↓ excretion of K+ & H+ .

Name: Spironolactone (Aldactone) Class: Diuretic (Potassium Sparing Diuretic) (Aldosterone Antagonist)

Absorption: Oral Dist.: Metab.: Excretion, t_: 1° = kidney. 6 hr. Toxicity/S.E.s: Hyperkalemia (most severe), n/v (most common), metabolic acidosis. Hyponatremia may occur in old folks. Absolutely contraindicated with hyperkalemia. Utility: Usu. given w/another diuretic (often thiazide or loop). Combination usu. → normal K+ excretion. Special Features: Rel. weak diuretic.

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Mech.: Competitive inhib. of aldosterone → block of aldost.-stim. Na+ reabsorption and K+ /H+ excretion in late distal tubule and collecting duct. Also reduces aldost.-stim. ammoniagenesis throughout the nephron. Absorption: Oral. Takes up to 2 days to be effective. Dist.: Metab.: Hepatic. Excretion, t_: 20 hr. Toxicity/S.E.s: Hyperkalemia, gynecomastia, amenorrhea. Absolutely contraindicated w/hyperkalemia. Utility: Most efficacious in pts. w/high plasma levels of aldosterone (e.g., 1° hyperaldosteronism due to an adrenal tumor or hyperplasia; 2° hyperaldost. due to cirrhosis, etc.). Special Features: Only diuretic that acts through the blood side of the tubule. Rel. weak diuretic.

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Name: Clonidine (Catapres) Class: Centrally Acting Antiadrenergic Agent/Opioid Withdrawal Suppressant Mech.: Stimulates inhibitory α2 receptors in central cardiovasc pathways involving EPI or NE. α2 are G-protein coupled to inhibit adenylyl cyclase → ↓ cAMP → ↓ central symp. activity. Absorption: Oral, transdermal. Dist.: Acts at medullary and spinal sites. Metab.: Excretion, t_: Toxicity/S.E.s: Prominent sedation, dry mouth, depression in those so inclined, constipation. S.E.s may be reduced by transdermal admin. May potentiate actions of other CNS depressants. Rebound hypertension, nervousness, insomnia if w/drawn too quickly. Utility: Treat hypertension. DOC for treating opioid w/drawal. No abstinence synd. when withdrawn. Special Features: Direct α2 activation. Very potent (<0.5 mg/day). CV reflexes remain intact; normal homeostatic responses to exercise are maintained.

Name: Guanabenz (Wytensin) Class: Centrally Acting Antiadrenergic Agent Mech.: Stimulates inhibitory α2 receptors in central cardiovasc pathways involving EPI or NE. α2 are G-protein coupled to inhibit adenylyl cyclase → ↓ cAMP → ↓ central symp. activity. Absorption: Oral. Dist.: Acts at medullary and spinal sites. Metab.: Excretion, t_: Toxicity/S.E.s: Prominent sedation, dry mouth, depression in those so inclined, constipation. May potentiate actions of other CNS depressants. Rebound hypertension, nervousness, insomnia if w/drawn too quickly. Utility: Treat hypertension. Special Features: Direct α2 activation. CV reflexes remain intact; normal homeostatic responses to exercise are maintained.

Name: Methyldopa (Aldomet) Class: Centrally Acting Antiadrenergic Agent

Name: Reserpine Class: Adrenergic Neuron Blocking Agent Mech.: Depletes NE, 5-HT, DA from nerve terminals in periph. and CNS. Also depletes some EPI from adrenal medulla. 1° = impairs storage of NE in terminals → ↓ NE available for release. Cause slow fall in BP, some bradycardia, slight inhib. of cardiovasc reflexes, inhib of catechol. release actions of indirect sympathomimetics, ↓ CO, ↓ TPR. Absorption: Oral Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Sedation, nightmares, psychic depression (suicide). In GI, parasymp tone predominates (cramps, diarrhea, exacerbated peptic ulcer). Nasal congestion, bradycardia. May potentiate effects of CNS depressants. Adverse interactions w/MAOIs. Utility: Treat mild-mod. hypertension (concurrent diuretic therapy). Periph. vasc. disease (Raynaud’s Synd.). Antipsychotic (seldom used; higher doses). Special Features: No longer considered very useful.

Mech.: Stimulates inhibitory α2 receptors in central cardiovasc pathways involving EPI or NE. α2 are G-protein coupled to inhibit adenylyl cyclase → ↓ cAMP → ↓ central symp. activity. Absorption: Dist.: Act at medullary and spinal sites. Metab.: Excretion, t_: Toxicity/S.E.s: Prominent sedation, dry mouth, nightmares, depression, movement disorders, endocrine disturbances (lactation), anemia, rare hypersensitivity of skin and liver. Possible toxic psychosis if given w/levodopa. Utility: Treat hypertension. Special Features: Activates α2 via metabolite methylnorepinephrine (false transmitter). Probably the most used hypotensive agent in mgt. of pregnant E.

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Name: Guanethidine (Ismelin) Class: Adrenergic Neuron Blocking Agent Mech.: Taken up at NE nerve terminal by NE transport system. Blocks release of NE by action potential or indirect agents. Eventually depletes NE. Causes ↓ BP, some bradycardia. No adrenal effect. Absorption: Poor oral. Dist.: No CNS. Metab.: Excretion, t_: 5 days. Toxicity/S.E.s: Marked postural & exercise hypotension, bradycardia, fluid retention, asthma aggravation, diarrhea, inhib. of ejaculation. But no CNS effects. C/I for pheochromocytoma (supersens), impending CHF or partial heart block, bronchial asthma. Not to be used in comb. w/MAO inhibitors or sympathomimetics. TCAs block uptake into nerve terminals. Utility: Mod.-severe hypertension (very effective, but last resort due to severe side effects). Special Features: Supersensitivity develops (↑ effect of direct acting, but ↓ effect of indirect). Onset 1-3 wks. No longer considered very useful.

Name: Prazosin (Minipress)

Name: Propranolol (Inderal) Class: Nonselective β-Blocking Agent Mech.: Competitive blockade of β1 and β2 receptors. No α effect. Decreases conversion of T4 to T3 by inhibiting hepatic monodeiodinase. Absorp.: Good oral (>90%). Low bioavail.: ~30%. Plasma levels vary 20x btwn. patients. Dist.:93% bound to protein. Enters CNS. Metab.: Hepatic Excret., t_: Short t_ (3.5-6 hr). Toxicity/S.E.s: CV—hypotension, bradycardia. C/i for AV. May exacerbate angina (unopposed α receptor action). Resp—c/i in asthmatics, COPD, bronchitis, allergic rhinitis. Metab—caution w/diabetics (masks sign of hypoglycemia: tachycardia). CNS—weakness, fatigue, nightmares, depression. GI—n/v (uncommon). Hypersens—rash, hematologic disorders (rare). Utility: Mild-mod HTN (↓ CO → ↓ BP; blocks renin release). Adjunct to direct vasodilators for severe HTN (prevents reflex tachycardia). Angina pectoris (prophylactic → ↑ exercise tolerance 2° to ↓ O2 demand). Cardiac arrhythmias (esp. supravent. tachyarrhyths). Acute MI (prophylaxis & reduction of infarct size and failure). Modifies risk factors assoc. w/atherosclerosis. Increases O2 delivery to ischemic cardiac tissue. Special Features: Abrupt w/drawal may trigger MI. Not as effective against variant angina as channel blockers and nitrates. Long-term antiarrhythmic β-blocker Rx → ↓ mortality.

Name: Nadolol (Corgard) Class: Nonselective β-Blocking Agent Mech.: Competitive blockade of β1 and β2 receptors. No α effect. Absorp.: Poor oral (>30%). Low bioavail: ~30%. Plasma levels vary 7x btwn. pts. Dist.: 30% bound to protein. Metab.: Excretion, t_: Renal. Long t_ (14-24 hr). Unchanged in urine. Toxicity/S.E.s: CV—hypotension, bradycardia, c/i for AV block. May exacerbate angina (unopposed α receptor action). Resp—c/i in asthmatics, COPD, bronchitis, allergic rhinitis. Metab—caution w/diabetics (masks sign of hypoglycemia: tachycardia). CNS—weakness, fatigue, nightmares, depression. GI—n/v (uncommon). Hypersens—rash, hematologic disorders (rare). Utility: Hypertension (↓ CO → ↓ BP; blocks renin release). Angina pectoris (prophylactic → ↑ exercise tolerance due to ↓ O2 demand). Cardiac arrhythmias (esp. supravent. tachyarrhyths). Acute MI (prophylaxis and reduction of infarct size and failure). Pheochromocytoma (in comb. w/alpha blocker). Essential tremor. Migraine headache (prophylaxis). Performance anxiety.

Class: α-Blocking Agent Mech.: Blocks α1 receptors in vasculature → ↓ phospholipase C activation, ↓ IP3 formation, ↓ Ca2+ released from intracellular stores → arteriolar & venous vasodilation. Absorption: Oral. 50% bioavailability Dist.: Metab.: Excretion, t_: 3 hr. Toxicity/S.E.s: 1st dose syncope (1%), dizziness, headaches, weakness. Utility: Treat periph. vasc. disease (Raynaud’s Disease), hypertension (lowers BP w/o producing sig. tachycardia), pheochromocytoma (phenoxybenz. is best), benign prostatic hyperplasia (relieves obstruction symptoms). Special Features: Prazosin-type α blockers are the only clinically useful antihypertensive α-receptor antagonists. Produce less tachycardia than do direct vasodilators. Readily combined w/other drugs.

Special Features: Abrupt w/drawal may trigger MI. Better pt. compliance than w/propranolol.

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Name: Timolol (Blocadren) Class: Nonselective β-Blocking Agent Mech.: Competitive blockade of β1 and β2 receptors. No α effect. Absorption: Good oral (>90%). High bioavailability ~75%. Plasma levels vary 7x btwn. patients. β-blocking plasma conc. 5-10 ng/mL (low). Eye drops. Dist.: 10% bound to protein. Excretion, t_: Hepatic, renal. Short t_ (3-4 hr). Toxicity/S.E.s: CV—hypotension, bradycardia, c/i for AV block. Resp—c/i in asthmatics, COPD, bronchitis, allergic rhinitis. Metab—caution w/diabetics (masks sign of hypoglycemia: tachycardia). CNS—weakness, fatigue, nightmares, depression. GI—n/v (uncommon). Hypersens—rash, hematologic disorders (rare). Utility: Hypertension (↓ CO → ↓ BP; blocks renin release). Angina pectoris (prophylactic → ↑ exercise tolerance due to ↓ O2 demand). Cardiac arrhythmias (esp. supravent. tachyarrhyths). Acute MI (prophylaxis and reduction of infarct size and failure). Pheochromocytoma (in comb. w/alpha blocker). Essential tremor. Migraine headache (prophylaxis). Performance anxiety. Eyedrops for open-angle glaucoma (↓ production of aqueous humor). Spec. Features: Abrupt w/drawal may trigger MI. 6-10x as potent orally as others.

Name: Pindolol (Visken)

Name: Metoprolol (Lopressor) Class: Cardioselective β1-Blocking Agent Mech.: Selective blockade of β1 (heart, kidney) w/rel. sparing of β2. No α effect. Absorption: Good oral (>95%). Bioavailability ~50%. Plasma levels vary 10x btwn. patients. Dist.: 12% bound to protein. Metab.: Hepatic Excretion, t_: Short t_ (3-4 hr). Toxicity/S.E.s: CV—hypotension, bradycardia, c/i for AV block. Resp—c/i in asthmatics, COPD, bronchitis, allergic rhinitis. Metab—caution w/diabetics (masks sign of hypoglycemia: tachycardia). CNS—weakness, fatigue, nightmares, depression. GI—n/v (uncommon). Hypersens—rash, hematologic disorders (rare). Utility: Hypertension (↓ CO → ↓ BP; blocks renin release). Angina pectoris (prophylactic → ↑ exercise tolerance due to ↓ O2 demand). Cardiac arrhythmias (esp. supravent. tachyarrhyths). Acute MI (prophylaxis and reduction of infarct size and failure). Pheochromocytoma (in comb. w/alpha blocker). Essential tremor. Migraine headache (prophylaxis). Performance anxiety. Special Features: Abrupt w/drawal may trigger MI. Cardioselectivity not great. May be advantageous in asthmatic or diabetic hypertensives.

Name: Labetalol (Trandate) Class: Nonselective β and α1 Blocking Agent Mech.: Competitive blockade of β1, β2, and α receptors. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: CV—orthostatic hypotension, sexual dysfxn, bradycardia, c/i for AV block. Resp—c/i in asthmatics, COPD, bronchitis, allergic rhinitis. Metab—caution w/diabetics (masks sign of hypoglycemia: tachycardia). CNS—weakness, fatigue, nightmares, depression. GI—n/v (uncommon). Hypersens—rash, hematologic disorders (rare). Also α effects. Utility: Hypertension (↓ CO → ↓ BP; blocks renin release). Angina pectoris (prophylactic → ↑ exercise tolerance due to ↓ O2 demand). Cardiac arrhythmias (esp. supravent. tachyarrhyths). Acute MI (prophylaxis and reduction of infarct size and failure). Pheochromocytoma (in comb. w/alpha blocker). Essential tremor. Migraine headache (prophylaxis). Performance anxiety. Features: Abrupt w/drawal may trigger MI. More α side effects. Widely used.

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Class: Nonselective β-Blocking Agent (Partial Agonist) Mech.: Partial agonists of β1 and β2 receptors. No α effect. Some intrinsic sympathomimetic activity. Absorption: Dist.: Excretion, t_: Toxicity/S.E.s: Mild chronic fatigue, low exercise tolerance, sedation, nightmares, depression, ↑ airway resistance (β2 effect). Utility: Hypertension (esp. HTN w/moderate bradycardia). Special Features: Much less effect on HR and CO compared to other β-blockers. Less disturbance of lipid and carbohydrate metab. compared to other β-blockers.

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Name: Captopril (Capoten) Class: ACE Inhibitor

Name: Enalapril (Vasotec) Class: ACE Inhibitor

Mech.: Inhib. production of angiotensin II → block of vasoconstriction and aldosterone stim. → ↓ TPR, ↓ Na+ /H20 retention → ↓ BP. Also blocks inactivation of bradykinin → vasodilation. Diminishes normal ↑ in epinephrine and aldosterone seen in CHF. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Postural hypotension, renal insufficiency, hyperkalemia, persistent dry cough, rash, angioneurotic edema. C/i in 2nd & 3rd trimesters of pregnancy. Prob. not a great idea for 1st trimester either.

Mech.: Inhib. production of angiotensin II → block of vasoconstriction and aldosterone stim. → ↓ TPR, ↓ Na+ /H20 retention → ↓ BP. Also blocks inactivation of bradykinin → vasodilation. Diminishes normal ↑ in epinephrine and aldosterone seen in CHF. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Postural hypotension, renal insufficiency, hyperkalemia, persistent dry cough, rash, angioneurotic edema. C/i in 2nd & 3rd trimesters of pregnancy. Prob. not a great idea for 1st trimester either.

Utility: Treat HTN, CHF, MI. Special Features:

Utility: Treat HTN, CHF, MI. Special Features: Inactive prodrug. Converted to enalaprilat (acts like captopril).

Name: Lisinopril (Zestril, Prinivol) Class: ACE Inhibitor

Name: Losartan (Cozaar) Class: Angiotensin II Antagonist

Mech.: Inhib. production of angiotensin II → block of vasoconstriction and aldosterone stim. → ↓ TPR, ↓ Na+ /H20 retention → ↓ BP. Also blocks inactivation of bradykinin → vasodilation. Diminishes normal ↑ in epinephrine and aldosterone seen in CHF. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Postural hypotension, renal insufficiency, hyperkalemia, persistent dry cough, rash, angioneurotic edema. C/i in 2nd & 3rd trimesters of pregnancy. Prob. not a great idea for 1st trimester either.

Mech.: Competitive inhib. of angiotensin II → smooth muscle relaxation (vasodilation), ↓ Na+ & H20, ↓ plasma volume → ↓ BP. Absorption: Oral. Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Hyperkalemia, fetal toxicity (c/i in 2nd & 3rd trimesters). Utility: Treat hypertension. Special Features: Angioneurotic edema and dry cough of ACE inhibitors not manifested.

Utility: Treat HTN, CHF, MI. Special Features: Lysine derivative of enalaprilat.

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Name: Lovastatin (Mevacor) Class: Blood Lipid-Lowering Agent (HMG CoA Reductase Inhibitor) Mech.: Inhib. of HMG CoA reductase → ↓ cholesterol pool, ↑ apoB/E receptor activity, ↑ LDL clearance. Large reduction of cholesterol and LDL. Little/no ↓ in TGs, little/no ↑ in HDL, no change in VLDL. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Common mild GI disturbances. Reversible elevations of liver enzymes in 4-7% (if AST or ALT > 3x normal, discontinue). Possible muscle damage—much more likely w/concurrent cyclosporine, gemfibrozil, niacin, or erythromycin; or if pt has hepatic disease, a severe infxn, or renal insufficiency. Continued use w/myopathy may → severe myositis, rhabdomyolysis, or acute renal failure. Can shorten sleep period by up to 18%. C/i in kids & preg. E. Utility: Treat pts. w/type IIA/IIB hyperlipidemia refractory to diet and other drugs. May not be useful for pts. w/homozygous familial hypercholesterolemia. Special Features: Most effective drug class for lowering LDL. Probably better tolerated than other cholesterol lowering drugs. Synergistic effects w/resins and niacin. If taken once/day, take at night (peak cholesterol synth. occurs between 12:00-3:00 a.m.).

Name: Pravastatin (Pravochol) Class: Blood Lipid-Lowering Agent (HMG CoA Reductase Inhibitor) Mech.: Inhib. of HMG CoA reductase → ↓ cholesterol pool, ↑ apoB/E receptor activity, ↑ LDL clearance. Large reduction of cholesterol and LDL. Little/no ↓ in TGs, little/no ↑ in HDL, no change in VLDL. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Common mild GI disturbances. Reversible elevations of liver enzymes in 4-7% (if AST or ALT > 3x normal, discontinue). Possible muscle damage—much more likely w/concurrent cyclosporine, gemfibrozil, niacin, or erythromycin; or if pt has hepatic disease, a severe infxn, or renal insufficiency. Continued use w/myopathy may → severe myositis, rhabdomyolysis, or acute renal failure. C/i in kids & preg. E. Utility: Treat pts. w/type IIA/IIB hyperlipidemia refractory to diet and other drugs. May not be useful for pts. w/homozygous familial hypercholesterolemia. Special Features: Most effective drug class for lowering LDL. Probably better tolerated than other cholesterol lowering drugs. Synergistic effects w/resins and niacin. If taken once/day, take at night (peak cholesterol synth. occurs between 12:00-3:00 a.m.).

Name: Simvastatin (Zocor) Class: Blood Lipid-Lowering Agent (HMG CoA Reductase Inhibitor) Mech.: Inhib. of HMG CoA reductase → ↓ cholesterol pool, ↑ apoB/E receptor activity, ↑ LDL clearance. Large reduction of cholesterol and LDL. Little/no ↓ in TGs, little/no ↑ in HDL, no change in VLDL. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Common mild GI disturbances. Reversible elevations of liver enzymes in 4-7% (if AST or ALT > 3x normal, discontinue). Possible muscle damage—much more likely w/concurrent cyclosporine, gemfibrozil, niacin, or erythromycin; or if pt has hepatic disease, a severe infxn, or renal insufficiency. Continued use w/myopathy may → severe myositis, rhabdomyolysis, or acute renal failure. Can shorten sleep period by up to 18%. C/i in kids & preg. E. Utility: Treat hyperlipidemia IIA/IIB refractory to diet and other drugs. May not be useful for pts. w/homozygous familial hypercholesterolemia. Special Features: Most effective drug class for lowering LDL. Probably better tolerated than other cholesterol lowering drugs. Synergistic effects w/resins and niacin. If taken once/day, take at night (peak cholesterol synth. occurs between 12:00-3:00 a.m.).

Name: Cholestyramine (Cholybar) Class: Blood Lipid-Lowering Agent (Resin) Mech.: Binds bile acids in intestine → ↑ defecation of bile acids, ↑ conversion of cholesterol to bile acids, ↓ pool of hepatic cholesterol, ↑ activity of apoB/E receptor, ↑ LDL clearance, ↓ plasma cholesterol. Moderate ↓ in cholesterol & LDL. Mild ↑ in HDL. Zero-moderate ↑ in TG & VLDL. Absorption: Oral. No absorption. Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Up to 50% refuse to continue Rx. Flatulence, constipation, gas, n/v, steatorrhea. Supersaturation of cholesterol in bile → gallstones, need for cholecystectomy. ↓ bile → ↓ absorption of lipid-soluble drugs/vitamins. Binds acidic drugs. Weak stim. of VLDL synth. Do not use in pts. w/hyperTG w/o concurrent TG-lowering agent. Utility: Treat hyperlipidemia IIA/IIB. Use alone or w/niacin, probucol, or HMG CoA reductase inhib. Special Features: GI S.E.s reduced if taken immediately prior to meals. _ dose + Metamucil™ → ↓ constipation & bloating, but sim. efficacy.

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Name: Colestipol (Colestid) Class: Blood Lipid-Lowering Agent (Resin) Mech.: Binds bile acids in intestine → ↑ defecation of bile acids, ↑ conversion of cholesterol to bile acids, ↓ pool of hepatic cholesterol, ↑ activity of apoB/E receptor, ↑ LDL clearance, ↓ plasma cholesterol. Moderate ↓ in cholesterol & LDL. Mild ↑ in HDL. Zero-moderate ↑ in TG & VLDL. Absorption: Oral. No absorption. Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Flatulence, constipation, gas, n/v, steatorrhea. Supersaturation of cholesterol in bile → gallstones, need for cholecystectomy. ↓ bile → ↓ absorption of lipid-soluble drugs/vitamins. Binds acidic drugs. Weak stim. of VLDL synth. Do not use in pts. w/hyperTG w/o concurrent TG-lowering agent. Utility: Treat hyperlipidemia IIA/IIB. Use alone or w/niacin, probucol, or HMG CoA reductase inhib. Special Features: GI S.E.s reduced if taken immediately prior to meals. _ dose + Metamucil™ → ↓ constipation & bloating, but sim. efficacy.

Name: Nicotinic Acid (Niacin) Class: Blood Lipid-Lowering Agent Mech.: Reduces synth. rate of VLDL. Inhib. lipolysis of TG in adipocytes. Large ↓ in TG. Moderate ↓ in cholesterol & VLDL. Mild ↓ in LDL. Zeromoderate ↑ in HDL. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Cutaneous flushing (92%), itching (49%), rashes (20%). Reduce w/aspirin pretreatment, admin. after meals, small init. dose gradually increased in size. Pruritis, dry skin, ↑ pigmentation, hepatotoxicity, n/v, dyspepsia, peptic ulceration, ↑ urinary frequency, dysuria, gout. High doses → hepatic/pancreatic dysfxn. Coadmin. anti-hypertensives → dizziness, syncope. Sustained-release preparations more commonly assoc. w/hepatotoxicity, dry eyes, ↑ pigmentation, hyperglycemia. Utility: Prob. DOC for hyperlipidemias IV and V. Very useful for III. Can be used for II. Synergy w/resins. Special Features:

Name: Gemfibrozil (Lopid) Class: Blood Lipid-Lowering Agent (Fibric Acid Derivative)

Name: Clofibrate (Atromid-S) Class: Blood Lipid-Lowering Agent (Fibric Acid Derivative)

Mech.: ↑ catabolism of VLDL, in part 2° to ↑ activity of lipoprotein lipase in adipose tissue. Moderate ↓ in TG & VLDL. Mild ↓ in LDL and cholesterol. Moderate ↑ in HDL.

Mech.: ↑ catabolism of VLDL, in part 2° to ↑ activity of lipoprotein lipase in adipose tissue. Moderate ↓ in TG & VLDL. Zero-mild ↓ in cholesterol. Zero-mild ↑ in HDL. Mild ↑ or ↓ in LDL.

Absorption: Dist.: Metab.: Glucuronide conjugation. Excretion, t_: Renal excretion. Toxicity/S.E.s: Generally well tolerated. GI distress, rash, musculoskeletal pain, blurred vision, anemia, leukopenia, gallstones. Adjust dose in pts. w/renal insufficiency. Utility: DOC for hyperlipidemia III. Better tolerated than niacin for type IV, although less effective. Decreases frequency of CHD-related incidents. Special Features:

Absorption: Dist.: Metab.: Glucuronide conjugation. Excretion, t_: Renal excretion. Toxicity/S.E.s: Generally well tolerated. Gallstones, nausea, diarrhea, abdominal discomfort. Displaces weakly acidic drugs (T3, T4, warfarin, phenytoin) from plasma proteins. Binds cholestyramine. Utility: Treat severe hyperlipidemia IV refractory to gemfibrozil or niacin. Special Features: Does not appear to decrease frequency of CHD-related incidents.

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Name: Probucol (Lorelco) Class: Blood Lipid-Lowering Agent (Fibric Acid Derivative) Mech.: Stim. LDL clearance by non-receptor pathways. May reduce risk of atherogenesis w/o altering serum cholesterol levels. May block oxidation of LDL. Moderate ↓ in cholesterol, LDL, & HDL. No effect on TG or VLDL. Absorption: Dist.: Stored in fat. Metab.: Excretion, t_: Toxicity/S.E.s: Generally very well tolerated (2-6% incidence). Flatulence, n/v/d, abd. pain, headache, rash. C/i in monkeys (cardiac arrhythmias). Stored in fat. ∴ E advised to wait 6 mo. after last dose before becoming pregnant. Utility: Treat hyperlipidemia IIA/IIB, but prob. not drug o’ first choice. May be useful for homozygous familial hypercholesterolemia (IIA). May cause regression of xanthomas. Special Features: ↓ in LDL takes 1-3 mo., but some pts. don’t respond. Does not further reduce LDL when used w/lovastatin.

Name: Nitroglycerin (Nitro-Bid) Class: Antianginal Agent (Organonitrate) Mech.: Converted to NO → activation of cytosolic guanylate cyclase → ↑ cGMP → activation of cGMP-dependent protein kinase → smooth muscle relaxation → vasodilation. Greater effect in veins & large arteries than in resistance vessels → ↓↓ preload, ↓ afterload → ↓ work → ↓ O2 demand. Inhib. of platelet fxn. Absorption: Sublingual preferred. IV. Oral → ↑ 1st pass metab, low bioavail. Buccal/transdermal → slow absorption. Dist.: Metab.: Hepatic (glutathione-organic nitrate reductase), extra-hepatic. Plasma clearance >> C.O. Excretion, t_: Renal. 3 min. Short duration of action (20-30 min.). Toxicity/S.E.s: Orthostatic hypotension, tachycardia, severe throbbing headache, dizziness, flushing, syncope. C/i w/elevated ICP. Utility: Treat angina. Subling. not suitable for maintenance therapy. IV for severe recurrent unstable angina. Oral/buccal/transdermal for prophylaxis, but may → tolerance. Special Features: 8+ hr. breaks necessary to avoid tolerance from slow absorp.

Name: Isosorbide Dinitrate (Isordil) Class: Antianginal Agent (Organonitrate) Mech.: Converted to NO → activation of cytosolic guanylate cyclase → ↑ cGMP → activation of cGMP-dependent protein kinase → smooth muscle relaxation → vasodilation. Greater effect in veins & large arteries than in resistance vessels → ↓↓ preload, ↓ afterload → ↓ work → ↓ O2 demand. Inhib. of platelet fxn. Absorption: Sublingual preferred → complete absorption. Oral → ↑ 1st pass metab, low bioavail. Buccal/transdermal → slow absorption. Dist.: Metab.: 80% converted to active metabolite 5-ISMN before entering systemic circulation. Hepatic inactivation via glutathione-organic nitrate reductase. Excretion, t_: Renal. 10 min. Short duration of action (20-30 min.). Toxicity/S.E.s: Orthostatic hypotension, tachycardia, severe throbbing headache, dizziness, flushing, syncope. C/i w/elevated ICP. Utility: Treat angina. Subling. not suitable for maintenance therapy. Oral/buccal/transdermal for prophylaxis, but may → tolerance Special Features: 8+ hr. breaks necessary to avoid tolerance from slow absorp.

Name: Amyl Nitrate Class: Antianginal Agent (Organonitrate)

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Mech.: Converted to NO → activation of cytosolic guanylate cyclase → ↑ cGMP → activation of cGMP-dependent protein kinase → smooth muscle relaxation → vasodilation. Greater effect in veins & large arteries than in resistance vessels → ↓↓ preload, ↓ afterload → ↓ work → ↓ O2 demand. Inhib. of platelet fxn. Absorption: Inhalation → rapid onset. Dist.: Metab.: Hepatic inactivation via glutathione-organic nitrate reductase. Excretion, t_: Renal. Short duration of action (3-5 min.). Toxicity/S.E.s: Orthostatic hypotension, tachycardia, severe throbbing headache, dizziness, flushing, syncope. C/i w/elevated ICP. Utility: Treat angina. Not suitable for maintenance therapy. Special Features:

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Name: Acetylsalicylic Acid (Aspirin) Class: Antithrombotic Agent (Antiplatelet Agent) Mech.: Irrevers. acetylation of cyclooxygenase → ↓ platelet thromboxane synth. Absorption: Oral → rapid absorption. Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: GI hemorrhage, hemorrhagic stroke. Use w/caution in pts on long-term oral anticoagulants. Hypersensitivity rxns—generalized urticaria, bronchial asthma, laryngeal edema, bronchoconstriction, hypotension, shock—may occur in 20-25% of pts w/asthma, nasal polyps, or chronic urticaria. Utility: Acute MI, stable/unstable angina, 2° prevention in MI survivors. TIA. 2° prevention in nondisabling ischemic stroke. Prevention of saphenous vein bypass graft occlusion. Post-coronary angioplasty. 1° MI prophylaxis (325 mg/d) adjunctive to risk factor management. Headache. Special Features: Low dose Rx optimal—75-325 mg/d. Antithrombotic use is primarily for arterial thromboses.

Name: Dipyridamole (Persantine) Class: Antithrombotic Agent (Antiplatelet Agent)

Name: Ticlopidine (Ticlid) Class: Antithrombotic Agent (Antiplatelet Agent) Mech.: Unknown. Through some effect on platelet membranes, blocks ADPinduced aggregation. Interacts w/membrane glycoprotein IIb/IIIa. Absorption: Dist.: Metab.: Excretion, t_:

Name: Abciximab (Reo-Pro) Class: Antithrombotic Agent (Antiplatelet Agent) Mech.: Monoclonal antibody to GPIIb/IIIa. Interferes w/platelet-adhesive protein interactions. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Utility: Treat high risk angioplasty pts. Special Features:

Toxicity/S.E.s: Diarrhea, GI cramping, rash, ↑ LDL & VLDL, leukopenia, agranulocytosis, pancytopenia. Utility: Treat thromboses in patients unable to take aspirin. May be more effective than aspirin in 2° prevention of stroke in pts w/previous TIA.

Mech.: Inhib. PDE in platelets → ↑ cAMP → inhib. of platelet activation. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Utility: Prevention of systemic embolism in pts. w/prosthetic heart valves. Admin. in combination w/warfarin. Special Features: When used alone, ineffective for Rx of cerebral or CV thrombotic events. Not proven to be of additional benefit when admin. w/aspirin. Antithrombotic use is primarily for arterial thromboses.

Special Features: Several days required for effects to develop. Effects persist for several days after cessation of treatment. As effective in E as in G. Antithrombotic use is primarily for arterial thromboses.

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Name: Heparin Class: Antithrombotic Agent (Anticoagulant) Mech.: Catalyzes complex formation btwn. plasma antithrombin III and various serine proteases of the coagulation pathway, including thrombin and activated factors IX, X, XI, & XII. Effect primarily due to thrombin inhib. Prevents further clot formation and thrombus propagation. Does not alter organized clots. Absorp.: IV, continuous IV→immed. onset. SC→1-2 hr onset w/variable bioavail. Dist.: Metab.: Hepatic. Excretion, t_: Rel. short t_. ↓ t_ w/pulm. embolism. ↑ t_ w/hepatic cirrhosis or end-stage renal disease. Toxicity/S.E.s: 1° = bleeding. Thrombocytopenia (bovine > porcine)—mild, severe (delayed onset; can occur w/heparin resistance → thromboembolism & DIC). Long-term use → osteoporosis. Non-teratogenic, but discontinue prior to delivery. Utility: Symptomatic calf vein thrombi or thrombi extending above the popliteal vein, pulm. embolus, atrial fibrillation, valvular heart disease, CAD, adjunct to post-MI thrombolytic therapy. Use in general surgery for E on oral contraceptives. Special Features: Primarily used for venous thromboses. Most widely used antithromb. agent. Monitor PTT to achieve desired dose—1.5-2.5x normal PTT is therapeutic. ↑ recurrence rate if PTT < 1.5 x normal or if therapeutic levels aren’t achieved w/in 24 hr. Few drug interactions.

Name: Enoxaparin (Lovenox) Class: Antithrombotic Agent (Anticoagulant) (Low Molecular Weight Heparin) Mech.: Catalyzes complex formation btwn. plasma antithrombin III and various serine proteases of the coagulation pathway, including thrombin and activated factors IX, X, XI, & XII. Effect primarily due to thrombin inhib. Less effect on thrombin than heparin. Prevents further clot formation and thrombus propagation. Does not alter organized clots. Absorp.: SC → better bioavail. than heparin. Daily SC injxn has sim. efficacy to 2-3 injxns/d of heparin. Dist.: Metab.: Hepatic. Excretion, t_: Longer t_ than heparin. ↓ t_ w/pulm. embolism. ↑ t_ w/hepatic cirrhosis or endstage renal disease. Toxicity/S.E.s: 1° = bleeding. Thrombocytopenia (bovine > porcine)—mild, severe (delayed onset; can occur w/heparin resistance → thromboembolism & DIC). Long-term use → osteoporosis. Non-teratogenic, but discontinue prior to delivery. Utility: 1° prevention of DVT after hip replacement surgery. Special Features: Primarily used for venous thromboses. Monitor PTT to achieve desired dose—1.5-2.5x normal PTT is therapeutic. ↑ recurrence rate if PTT < 1.5 x normal or if therapeutic levels aren’t achieved w/in 24 hr. Few drug interactions. Lower rate of bleeding than w/heparin.

Name: Protamine Sulfate Class: Anticoagulant Antagonist Mech.: Binds tightly to heparin and rapidly reverses its effects. Also interacts w/platelets, fibrinogen, and other plasma proteins → anticoagulant effect. Absorption: IV infusion—slow rate. Dist.: Metab.: Excretion, t_: Toxicity/S.E.s:

Name: Antithrombin III (ATnativ) Class: Antithrombotic Agent (Coagulation Inhibitor) Mech.: Prepared from pooled human plasma. Inhibits coagulation factors (thrombin, IXa, Xa, XIIa). Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Utility: Treat pts w/hereditary AT-III deficiency and neonates w/a family history of AT-III deficiency. Prophylaxis for deficient pts who are undergoing surgery or delivery at term. Special Features:

Utility: Treat life-threatening hemorrhage 2° to heparin use. Special Features: Use minimal effective dose.

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Name: Warfarin (Coumadin) Class: Antithrombotic Agent (Oral Anticoagulant)

Name: Vitamin K1 (Phytonadione) Class: Anticoagulant Antagonist

Mech.: Vitamin K antagonist → ↓ γ-carboxylation of thrombin, factors, VII, IX, & X, and proteins C & S → inhib. of synth. of active coagulation factors. Does not alter organized clots. Absorption: Oral. Dist.: Almost completely bound (99%) to plasma proteins (mainly albumin). Metab.: Microsomal enzymes in liver and kidneys. Excretion, t_: Urine and stool. Toxicity/S.E.s: Hemorrhage, hypersensitivity rxns., fetal toxicity. “Purple Toe” synd. (necrosis) assoc. w/protein C deficiency. During pregnancy, can cause birth defects and abortion. Many drug interactions. Utility: Prevention of recurrent thrombotic events following acute Rx w/heparin. Valvular heart disease, prosthetic cardiac valves, AMI, atrial fibrillation. Special Features: Max. effects require 2-7 days. Init. response may be procoagulant due to inhib. of protein C. Should have 6 day overlap w/heparin. Monitor PT.

Mech.: Vit. K is necessary for γ-carboxylation of thrombin, factors VII, IX, & X, and proteins C & S. The γ-carboxylated residues are required for binding Ca2+, which is essential for their activity. Absorption: Oral or SC preferred. IV admin. may cause shock or anaphylaxis. Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: IV admin. may cause shock or anaphylaxis. Utility: Reverse excessive bleeding due to warfarin—indicated for severe or continued bleeding if warfarin dosage adjustment is unsuccessful. Special Features: Significant improvement in hemostasis may require as long as 24 hr. If immediate hemostasis is necessary, fresh frozen plasma should be infused.

Name: Streptokinase (Streptase) Class: Antithrombotic Agent (Thrombolytic Agent) Mech.: Derived from β-hemolytic streptococci. Forms a complex w/plasminogen, exposing its active site. Poor thrombus specificity—catalyzes conversion of circulating and fibrin-bound plasminogen—results in a systemic lytic state. Absorption: IV. Admin. w/large loading dose to overcome plasma antibodies. Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Hemorrhage. Allergic rxns—pruritis, flushing, urticaria. Higher incidence of allergic rxns. w/readministration. Pronounced hypotension (usu. transient). Delayed fever and arthralgia. Utility: Treat acute MI (w/in 6 hr. of symptoms), massive PE, acute proximal vein thromboses, occlusion of dialysis access sites and indwelling catheters, occlusion of prosthetic heart valves. Special Features: Best results in pts. that receive therapy < 1 hr. after onset of symptoms and that achieve successful reperfusion. Pts. w/antibodies can develop therapeutic resistance.

Name: Anistreplase/APSAC (Eminase) Class: Antithrombotic Agent (Thrombolytic Agent) Mech.: Acylated plasminogen-streptokinase activator complex. Plasminogen active site is protected from inactivation. Poor thrombus specificity—catalyzes conversion of circulating & fibrin-bound plasminogen—results in a systemic lytic state. Absorption: IV. Admin. w/large loading dose to overcome plasma antibodies. Dist.: Metab.: Excretion, t_: Longer t_ than streptokinase → sustained fibrinolytic effect. Toxicity/S.E.s: Hemorrhage. Allergic rxns—pruritis, flushing, urticaria. Higher incidence of allergic rxns. w/readministration. Pronounced hypotension (usu. transient). Delayed fever and arthralgia. Utility: Treat acute MI (w/in 6 hr. of symptoms), massive PE, acute proximal vein thromboses, occlusion of dialysis access sites and indwelling catheters, occlusion of prosthetic heart valves. Special Features: Best results in pts. that receive therapy < 1 hr. after onset of symptoms and that achieve successful reperfusion. Pts. w/antibodies can develop therapeutic resistance.

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Name: Tissue Plasminogen Activator, tPA (Activase) Class: Antithrombotic Agent (Thrombolytic Agent) Mech.: Recombinant product identical to endothelial tPA. Preferentially activates plasminogen that is bound to fibrin → greater clot specificity and potentially less systemic fibrinolysis than w/streptokinase. Absorption: IV. Prolonged admin. necessary (generally given over 3 hr.). “Accelerated” regimen admin. over 90 min. (2/3 given w/in 1st 30 min.) Dist.: Metab.: Excretion, t_: Short t_. Toxicity/S.E.s: Hemorrhage. Utility: Treat acute MI (w/in 6 hr. of symptoms), massive PE, acute proximal vein thromboses, occlusion of dialysis access sites and indwelling catheters, occlusion of prosthetic heart valves. Special Features: Best results in pts. that receive therapy < 1 hr. after onset of symptoms and that achieve successful reperfusion. Expensive—several times more costly than streptokinase.

Name: Urokinase (Abbokinase) Class: Antithrombotic Agent (Thrombolytic Agent) Mech.: Urinary-type single chain plasminogen activator. Isolated from cultured human kidney cells. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Hemorrhage. Utility: Treat acute MI (w/in 6 hr. of symptoms), massive PE, acute proximal vein thromboses, occlusion of dialysis access sites and indwelling catheters, occlusion of prosthetic heart valves. Special Features: Best results in pts. that receive therapy < 1 hr. after onset of symptoms and that achieve successful reperfusion. Generally nonantigenic. Does not cause allergic rxns.

Name: Aminocaproic Acid (Amicar) Class: Thrombolytic Agent Antagonist

Name: Tranexamic Acid (Amstat) Class: Thrombolytic Agent Antagonist Mech.: Competitive inhib. of plasminogen activation. Absorption: Oral. Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Utility: Used for hemostasis in pts. undergoing oral surgery who are being treated w/oral anticoagulants. Special Features:

Mech.: Lysine analog. Binds to lysine sites on plasminogen and plasmin → blocks binding of plasmin to fibrin. Absorption: IV (slow injxn). Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Thrombi that form during treatment are not lysed. Thrombosis may become a problem. Utility: Treat bleeding from fibrinolytic therapy. Special Features:

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Name: Quinidine (Quinidex) Class: Antidysrhythmic Agent (Class IA) Mech.: Binds to open and inactivated Na+ channels and prevents Na+ influx → slowing of the rapid upstroke during phase 0. Also decreases the slope of phase 4 spontaneous depolarization. Prolongs repolarization. Inhibits arrhythmias due to ↑ normal automaticity. Intermed. speed of dissociation from Na+ channels. Absorption: Oral → rapid, nearly complete absorption. Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Proarrhythmic effects, negative inotropy, infranodal conduction block, DILQT. Cinchonism—n/v/d, tinnitus, headache, vertigo, auditory/visual disturbances. Hypotension (α-blocking activity). ↑ digoxin levels. Hypersensitivity rxns—rash, fever, angioneurotic edema, hepatitis. Reversible thrombocytopenia. Utility: Treat atrial, AV junctional, & ventricular tachyarrhythmias. Maintain sinus rhythm after direct current cardioversion of atrial flutter or fibrillation. Prevent frequent ventricular tachycardia. Special Features:

Name: Procainamide (Pronestyl) Class: Antidysrhythmic Agent (Class IA) Mech.: Binds to open and inactivated Na+ channels and prevents Na+ influx → slowing of the rapid upstroke during phase 0. Also decreases the slope of phase 4 spontaneous depolarization. Prolongs repolarization. Inhibits arrhythmias due to ↑ normal automaticity. Intermed. speed of dissociation from Na+ channels. Absorption: Oral. IV rarely used, as hypotension occurs w/too rapid infusion. Dist.: Excretion, t_: Urine. 2-3 hr. Metab.: Hepatic → active metabolite NAPA (↑ duration of action potential). Toxicity/S.E.s: Proarrhythmic effects, negative inotropy, infranodal conduction block, DILQT. Hypotension (ganglion-blocking activity). Chronic use → reversible SLE-like synd. Depression, hallucination, psychosis, giddiness. Less GI intolerance than quinidine. Hypersensitivity rxns—fever, agranulocytosis, Raynaud’s synd., myalgias, rashes, digital vasculitis. Utility: Treat atrial, AV junctional, & ventricular tachyarrhythmias. Maintain sinus rhythm after direct current cardioversion of atrial flutter or fibrillation. Prevent frequent ventricular tachycardia. Special Features:

Name: Disopyramide (Norpace) Class: Antidysrhythmic Agent (Class IA) Mech.: Binds to open and inactivated Na+ channels and prevents Na+ influx → slowing of the rapid upstroke during phase 0. Also decreases the slope of phase 4 spontaneous depolarization. Prolongs repolarization. Inhibits arrhythmias due to ↑ normal automaticity. Intermed. speed of dissociation from Na+ channels. Peripheral vasoconstriction. The stereoisomers have opposite effects on repolarization. Absorption: Dist.: Metab.: Hepatic. Excretion, t_: Urine. Toxicity/S.E.s: Proarrhythmic effects, negative inotropy, infranodal conduction block, DILQT. Anticholinergic effects—dry mouth, urinary retention, blurred vision, constipation. N/v/d, abd. pain. Less GI intolerance than quinidine. Utility: Alt. to procainamide or quinidine for treatment of ventricular arrhythmia. Special Features:

Name: Lidocaine (Zylocaine) Class: Antidysrhythmic Agent (Class IB) Mech.: Shortens phase 3 repolarization. Little change in action potential duration. Inhibits arrhythmias caused by abnormal automaticity. Rapid speed of dissociation from Na+ channels. Absorption: IV Dist.: Metab.: Hepatic. Excretion, t_: Toxicity/S.E.s: Fairly wide therapeutic index. Proarrhythmic effects, negative inotropy, infranodal conduction block. Drowsiness, slurred speech, paresthesia, agitation, confusion, convulsions, resp. depression, tinnitus, muscle twitching, psychosis, seizures. ↑ CNS toxicity if used w/tocainide or mexiletine (e.g., seizures). Utility: DOC for sustained ventricular tachycardia. Treat ventricular arrhythmias arising during myocardial ischemia or digitalis-induced VA. Special Features: Class IB drugs have the lowest potency as Na+ channel blockers.

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Name: Tocainide (Tonocard) Class: Antidysrhythmic Agent (Class IB) Mech.: Shortens phase 3 repolarization. Little change in action potential duration. Inhibits arrhythmias caused by abnormal automaticity. Rapid speed of dissociation from Na+ channels. Absorption: Oral Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Proarrhythmic effects, negative inotropy, infranodal conduction block. N/v, dizziness, disorientation, tremor. Hematologic effects (agranulocytosis, bone marrow suppression, thrombocytopenia) can be fatal. Utility: Treat ventricular tachyarrhythmias (only as a last resort). Special Features: Concurrent use w/quinidine may be effective at lower doses than either alone → ↓ adverse effects of each.

Name: Mexiletine (Mexitil) Class: Antidysrhythmic Agent (Class IB) Mech.: Shortens phase 3 repolarization. Decreases action potential duration. Inhibits arrhythmias caused by abnormal automaticity. Rapid speed of dissociation from Na+ channels. Absorption: Oral Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Proarrhythmic effects, negative inotropy, infranodal conduction block. N/v, dizziness, disorientation, tremor. Utility: Chronic treatment of ventricular arrhythmias assoc. w/previous myocardial infarction. Special Features: Concurrent use w/quinidine may be effective at lower doses than either alone → ↓ adverse effects of each.

Name: Flecainide (Tambocor) Class: Antidysrhythmic Agent (Class IC) Mech.: Slow dissociation from Na+ channels → marked suppression of phase 0 upstroke → marked slowing of conduction. ↑ threshold potential → ↓ automaticity. Absorption: Oral. Dist.: Metab.: Minimal. Excretion, t_: 16-20 hr. Toxicity/S.E.s: Long-term Rx → ↑ mortality. Dizziness, blurred vision, tremor, agitation, headache, nausea. Aggravation of preexisting arrhythmias, negative inotropy, induction of life-threatening ventricular tachycardia (CAST proarrhythmia), aggravation of CHF, infranodal conduction block. Utility: Treat refractory ventricular arrhythmias. Suppress premature ventricular contraction. Treat AV nodal reentry, WPW-related arrhythmia. Special Features: Class IC drugs have the highest potency as Na+ channel blockers

Name: Sotalol (Betapace) Class: Antidysrhythmic Agent (Class III)

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Mech.: Blocks rapid outward K+ current (delayed rectifier) → prolonged repolarization and action potential → ↑ effective refractory period. Little effect on rate of depolarization. L-isomer is a potent β-blocker. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Rel. low rate of adverse effects. DILQT synd., sinus bradycardia. Utility: Long-term therapy to decrease the rate of sudden death following acute MI. Modest ability to suppress ectopic beats and ↓ O2 demand. Strong antifibrillary effect. Prevents arrhythmia and decreases mortality in pts. w/sustained ventricular tachycardia. Special Features:

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Name: Amiodarone (Cordarone) Class: Antidysrhythmic Agent (Class III) Mech.: Structurally related to thyroxine. 1° effect is prolongation of action potential and refractory period. Antiarrhythmic activity and antianginal activity. Absorption: Oral. Dist.: Metab.: Excretion, t_: 25-110 days. Toxicity/S.E.s: Common (>75% of pts). Interstitial pulmonary fibrosis, GI intolerance, tremor, ataxia, dizziness, depression, nightmares, hallucinations, hyper/hypothyroidism, liver toxicity, photosensitivity, periph. neuropathy, muscle weakness, blue skin (I2), possibly irreversible hepatic dysfxn. DILQT synd., sinus bradycardia. Asympt. corneal deposits in all pts. Substantial ↑ in LDL. Phospholipidosis. Enhances effect of warfarin. ↑ conc. of digoxin, quinidine, procainamide, et. al. Utility: Treat severe refractory supraventricular and ventricular tachyarrhythmia. Special Features: Usefulness limited by toxicity. Full effects may take up to 6 weeks to manifest.

Name: Magnesium Class: Antidysrhythmic Agent Mech.: Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Utility: DOC for torsades de pointes (DILQT synd). Treat pts w/digitalisinduced arrhythmia if hypomagnesemia is present. Special Features:

Name: Adenosine (Adrenocard) Class: Antidysrhythmic Agent Mech.: High doses → ↓ conduction velocity, ↑ refractory period, ↓ automaticity in the AV node. Absorption: IV Dist.: Metab.: Excretion, t_: Extremely short duration of action (15 sec.). Toxicity/S.E.s: Low toxicity. Flushing, chest pain, hypotension, transient dyspnea, non-myocardial chest discomfort, metallic taste. Utility: DOC for acute supraventricular tachycardia. Treat AV nodal reentry, orthodromic tachycardia. Special Features:

Hope. Pandora brought the box containing the evils and opened it. It was the gift of the gods to mankind, outwardly a fair, seductive gift and named the ‘box of good fortune’. Then all the evils, living winged creatures, flew out; since then they have been hovering about doing harm to men by day and night. A single evil had not yet slipped out of the box; then, by the will of Zeus, Pandora shut the lid, and thus it remained within. Now man has the box of good fortune forever in the house and is amazed at the treasure he possesses in it; it stands at his service, he reaches for it when he desires to do so; for he does not know that the box Pandora brought was the box of evil and regards the evil that has remained behind as the greatest piece of good fortune - it is hope. For what Zeus wanted was that man, though never so tormented by the other evils, should nonetheless not throw life away but continue to let himself be tormented. To that end he gives men hope: it is in truth the worst of all evils, because it protracts the torment of men. - Nietzsche

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Name: Thyroglobulin (Proloid) Class: Thyroid Hormone Mech.: T3/T4 synergize w/GH effects, increase BMR, potentiate catecholamine effects on heart, promote lipolysis, and decrease serum cholesterol. Absorption: Oral Dist.: Poor placental transfer → okay for pregnant E. Little in milk (use cautiously). Metab.: T4 & T3 released by proteolysis after ingestion. Hepatic conjug. of T4/T3 w/glucuronic & sulfuric acids. Excretion, t_: Bile; some lost in stool due to enterohepatic circulation. Toxicity/S.E.s: Salicylates and dicumarol compete for albumin binding sites → marked increase of free levels. Utility: Treat hypothyroidism and goiter (not due to iodine deficiency or hyperthyroidism). Special Features: 120-180 mg/d. Similar efficacy to levothyroxine sodium and liothyronine sodium, although dose not standardized by bioassay.

Name: Levothyroxine sodium (Synthroid, Levothroid, Levoxine) Class: Thyroid Hormone Mech.: Sodium salt of T4. T3/T4 synergize w/GH effects, increase BMR, potentiate catecholamine effects on heart, promote lipolysis, and decrease serum cholesterol. Absorption: Incomplete oral absorption—30-40% recovered in stool. Dist.: Poor placental transfer → okay for pregnant E. Little in milk (use cautiously). Metab.: Hepatic conjug. w/glucuronic & sulfuric acids. Peripheral deiodination to T3. Excretion, t_: Bile; some lost in stool due to enterohepatic circ. 6-7 d. Toxicity/S.E.s: Salicylates and dicumarol compete for albumin binding sites → marked increase of free levels. Utility: Treat hypothyroidism and goiter (not due to iodine deficiency or hyperthyroidism). Special Features: 200-300 µg/d. 1/4 the potency of liothyronine sodium, but same efficacy.

Name: Liothyronine sodium (Cytomel) Class: Thyroid Hormone Mech.: Sodium salt of T3. T3/T4 synergize w/GH effects, increase BMR, potentiate catecholamine effects on heart, promote lipolysis, and decrease serum cholesterol.

Name: Propylthiouracil (PTU) Class: Antithyroid Drug (Thioamide) Mech.: Blocks thyroid synthesis.

Absorption: Oral → 95% absorption.

Dist.: 80% protein binding. Poor placental transfer. 10% transfer into milk. Metab.: Conjugated to gluconamide. Excretion, t_: 35% excreted in urine, mostly as gluconamide. 1-2 hr. Toxicity/S.E.s: 3% freq. of untoward rxns. Most common = rash. 0.44% develop agranulocytosis. Occurs suddenly in first months of therapy, preceded by a sore throat and fever. Unusual bleeding and bruising may occur. C/i in nursing mothers, but can be used (w/great caution) in pregnancy-complicated hyperthyroidism (may cause neonatal goiter).

Dist.: Poor placental transfer → okay for pregnant E. Little in milk (use cautiously). Metab.: Hepatic conjug. w/glucuronic & sulfuric acids. Excretion, t_: Bile; some lost in stool due to enterohepatic circ. ≤ 2 d. Toxicity/S.E.s: Salicylates and dicumarol compete for albumin binding sites → marked increase of free levels. Utility: Preferred in treatment of myxedema coma. Treat hypothyroidism and goiter (not due to iodine deficiency or hyperthyroidism). Special Features: 50-75 µg/d. 4x the potency of levothyroxine sodium, but same efficacy.

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Absorption: Oral → 80-95% bioavailability.

Utility: Treat hyperthyroidism, but relapse after single course ≥ 50%. Special Features: 75-100 mg/8 hr (or higher).

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Name: Methimazole (Tapazole) Class: Antithyroid Drug (Thioamide) Mech.: Blocks thyroid synthesis. Absorption: Oral → 80-95% bioavailability. Dist.: 0% protein binding. High placental transfer. 100% transfer into milk. Metab.: Conjugated to gluconamide. Excretion, t_: <10% excreted in urine, mostly as gluconamide. 3-5 hr. Toxicity/S.E.s: 7% freq. of untoward rxns. Most common = rash. 0.12% develop agranulocytosis. Occurs suddenly in first months of therapy, preceded by a sore throat and fever. Unusual bleeding and bruising may occur. C/i in nursing mothers, but can be used (w/great caution) in pregnancy-complicated hyperthyroidism (may cause neonatal goiter); PTU is safer. Utility: Treat hyperthyroidism, but relapse after single course ≥ 50%.

Name: Iodide Class: Antithyroid drug Mech.: High doses of iodide inhibit thyroid gland fxn. Effects decrease w/time, possible due to decrease in iodide transport. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Utility: Used in conjunction w/thioamides for preoperative preparation to diminish vascularity and swelling of thyroid gland → reduced operative mortality. Treatment of thyrotoxicosis. Blocks synthesis and release of thyroid hormones. Rapid effect. Special Features: No longer used very much.

Special Features: 5-10 mg/8 hr (or higher).

Name: Radioactive Iodine Class: Antithyroid Drug Mech.: Trapped by thyroid. β particles cause highly localized tissue destruction. X-rays are diagnostically useful. I131 generally used due to short t_ (8 d). Absorption: 90% ends up in thyroid or urine. 10% absorbed by the rest of the organ systems. Dist.: Metab.: Excretion, t_: Urine. 8 d. Toxicity/S.E.s: High incidence of hypothyroidism (5-10% in 1-2 yr., eventually 50%). May require multiple exposures—up to a year (thioamides usu. used to cover hyperthyroidism in the interim). C/i in pregnant E and kids. Utility: Treat hyperthyroidism w/o surgery. Indicated for old folk (esp. w/heart disease), when subtotal thyroidectomy or thioamides have not worked, and especially for some metastatic thyroid cancers where cells continue to take up iodide and respond to TSH. Used to evaluate thyroid fxn (e.g., hypo/hyperthyroidism, goiter types, response to TSH/TRF.). Special Features: Min. dose = 80-150 µCi/g thyroid or 4-10 mCi total. Estimate w/tracer dose to determine uptake.

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Name: Propranolol (Inderal) Class: Nonselective β-Blocking Agent Mech.: Competitive blockade of β1 and β2 receptors. No α effect. Decreases conversion of T4 to T3 by inhibiting hepatic monodeiodinase. Absorption: Good oral (>90%). But low bioavailability ~30%. Plasma levels vary 20x btwn. patients. Dist.:93% bound to protein. Enters CNS. Metab.: Hepatic Excret., t_: Short t_ (3.5-6 hr). Toxicity/S.E.s: CV—hypotension, bradycardia, c/i for CHF or AV block. Resp—c/i in asthmatics, COPD, bronchitis, allergic rhinitis. Metab—caution w/diabetics (masks sign of hypoglycemia: tachycardia). CNS—weakness, fatigue, nightmares, depression. GI—n/v (uncommon). Hypersens—rash, hematologic disorders (rare). Utility: Hypertension (↓ CO → ↓ BP; blocks renin release). Angina pectoris (prophylactic → ↑ exercise tolerance due to ↓ O2 demand). Cardiac arrhythmias (esp. supravent. tachyarrhyths). Acute MI (prophylaxis and reduction of infarct size and failure). Pheochromocytoma (in comb. w/alpha blocker). Essential tremor. Migraine headache (prophylaxis). Performance anxiety. Thyrotoxicosis—Suppression of signs/symptoms of thyrotoxicosis. Most effective drug for treatment of thyrotoxic crisis or thyroid storm (usu. used in comb w/a thioamide and/or iodide. Can be used preop. for thyroid surg. Controversial Rx of hyperthyroid symptoms while awaiting effects of thioamides or iodide. Special Features: Abrupt w/drawal may trigger MI.

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Name: Calcium gluconate (Kalcinate) Class: Element Mech.: Absorption: Slow IV infusion. Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Major = hypercalcemia (esp. during long-term therapy or coadmin. w/vit. D). Hypercalciuria. Rapid infusion may cause cardiac arrhythmias. Enhances action of digitalis. ∴ IV infusion may ppt arrhythmias. Drug interactions—↓ bioavailability and/or oral absorption of some drugs (e.g., etidronate, tetracyclines, iron salts, atenolol, norfloxacin). Thiazide diuretic-induced hypercalcemias exacerbated by calcium supplementation. Utility: DOC for severe hypocalcemia. Reduces/prevents bone loss in older women (800 mg/d). Special Features: 9% calcium.

Name: Calcium gluceptate Class: Element Mech.: Absorption: IV (IM if IV is infeasible). Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Major = hypercalcemia (esp. during long-term therapy or coadmin. w/vit. D). Hypercalciuria. More irritating than calcium gluconate. May cause mild local rxns (e.g., tingling). Metallic taste. Enhances action of digitalis. ∴ IV infusion may ppt arrhythmias. Drug interactions—↓ bioavailability and/or oral absorption of some drugs (e.g., etidronate, tetracyclines, iron salts, atenolol, norfloxacin). Thiazide diuretic-induced hypercalcemias exacerbated by calcium supplementation. Utility: Treat hypocalcemia. Reduces/prevents bone loss in older women (800 mg/d). Special Features: 8% calcium.

Name: Calcium chloride Class: Element Mech.: Absorption: IV. Never inject IM (highly irritating). Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Major = hypercalcemia (esp. during long-term therapy or coadmin. w/vit. D). Hypercalciuria. Enhances action of digitalis. ∴ IV infusion may ppt arrhythmias. High level of irritation (esp. IM). Drug interactions—↓ bioavailability and/or oral absorption of some drugs (e.g., etidronate, tetracyclines, iron salts, atenolol, norfloxacin). Thiazide diuretic-induced hypercalcemias exacerbated by calcium supplementation. Utility: Treat hypocalcemia. Reduces/prevents bone loss in older women (800 mg/d). Special Features: 27% calcium. Probably obsolete due to greater irritation (enteral or parenteral admin.) than other calcium preparations.

Name: Calcium carbonate (TUMS, etc.) Class: Element Mech.: Absorption: Oral usu. → 15-20% (up to 50% w/maximal stimulation). Depends of stomach acid for solubilization. ∴ Absorption is impaired in anchlorhydric or fasting patients. Absorption improved when taken w/food. Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Hypercalcemia, hypercalciuria. Drug interactions—↓ bioavailability and/or oral absorption of some drugs (e.g., etidronate, tetracyclines, iron salts, atenolol, norfloxacin). Thiazide diuretic-induced hypercalcemias exacerbated by calcium supplementation. Utility: Treat mild hypocalcemia. Also maintenance after initial IV treatment. Provide 400-800 mg/d. Reduces/prevents bone loss in older women (800 mg/d). Special Features: 40% calcium.

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Name: Calcium citrate (Citracal, etc.) Class: Element Mech.: Absorption: Oral usu. → 15-20% (up to 50% w/maximal stimulation). Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Hypercalcemia, hypercalciuria. Drug interactions—↓ bioavailability and/or oral absorption of some drugs (e.g., etidronate, tetracyclines, iron salts, atenolol, norfloxacin). Thiazide diuretic-induced hypercalcemias exacerbated by calcium supplementation. Utility: Treat mild hypocalcemia. Also maintenance after initial IV treatment. Provide 400-800 mg/d. Reduces/prevents bone loss in older women (800 mg/d). Special Features: 21% calcium. More soluble than calcium carbonate. Works better in anchlorhydrics.

Name: Calcium glubionate (Neo-Calglucon) Class: Element Mech.: Absorption: Oral usu. → 15-20% (up to 50% w/maximal stimulation). Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Hypercalcemia, hypercalciuria, diarrhea. Drug interactions—↓ bioavailability and/or oral absorption of some drugs (e.g., etidronate, tetracyclines, iron salts, atenolol, norfloxacin). Thiazide diuretic-induced hypercalcemias exacerbated by calcium supplementation. Utility: Treat mild hypocalcemia. Also maintenance after initial IV treatment. Provide 400-800 mg/d. Reduces/prevents bone loss in older women (800 mg/d). Special Features: 6.5% calcium. Probably obsolete due to large number of tablets necessary to obtain effect.

Name: Calcium lactate Class: Element Mech.: Absorption: Oral usu. → 15-20% (up to 50% w/maximal stimulation). Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Hypercalcemia, hypercalciuria. Drug interactions—↓ bioavailability and/or oral absorption of some drugs (e.g., etidronate, tetracyclines, iron salts, atenolol, norfloxacin). Thiazide diuretic-induced hypercalcemias exacerbated by calcium supplementation. Utility: Treat mild hypocalcemia. Also maintenance after initial IV treatment. Provide 400-800 mg/d. Reduces/prevents bone loss in older women (800 mg/d). Special Features: 13% calcium. Probably obsolete due to large number of tablets necessary to obtain effect.

Name: Tribasic calcium phosphate Class: Element Mech.: Absorption: Oral. Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Ectopic calcification, kidney failure, death. Serum calcium and phosphate should be monitored to avoid hypocalcemia and hyperphosphatemia. Utility: Treat simultaneous hypocalcemia and hypophosphatemia. Special Features: 39% tribasic calcium phosphate.

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Name: Dicalcium phosphate Class: Element Mech.: Absorption: Oral. Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Ectopic calcification, kidney failure, death. Serum calcium and phosphate should be monitored to avoid hypocalcemia and hyperphosphatemia. Utility: Treat simultaneous hypocalcemia and hypophosphatemia. Special Features: 23% dibasic calcium phosphate dihydrate.

Name: Sodium phosphate oral solution Class: Element Mech.: Absorption: Oral Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Ectopic calcification, kidney failure, death. Serum calcium and phosphate should be monitored to avoid hypocalcemia and hyperphosphatemia. Utility: Primarily reserved for patients w/X-linked familial hypophosphatemia or other forms of osteomalacia featuring hypophosphatemia. Special Features: Safer than IV sodium/potassium phosphate. Sodium-free preparations are available (K-Phos Original, Neutra-Phos K).

Name: Sodium or potassium phosphate Class: Element Mech.: Absorption: IV Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Ectopic calcification, kidney failure, death. Serum calcium and phosphate should be monitored to avoid hypocalcemia and hyperphosphatemia. Utility: Treat hypophosphatemia. Special Features: More dangerous than sodium phosphate oral solution.

Name: Vitamin D2/ergocalciferol (Deltalin, Drisdol, Calciferol) Class: Vitamin Mech.: Increases intestinal absorption of calcium and phosphate. Stimulates bone resorption by facilitating effects of PTH. Stimulates renal reabsorption of calcium and phosphate. Net result = ↑↑ calcium, ↑↑ phosphate. Absorption: Oral usu → adequate absorption. Bile is essential for absorption. Dist.: Stored in fat and muscle. Tightly bound to vitamin D-binding protein. Metab.: Requires hydroxylation in liver and kidney for full activity. Excretion, t_: 1° = bile. Weeks. Toxicity/S.E.s: Excess accumulation in fat/muscle, hypervitaminosis D, hypercalcemia. Drug interactions—phenytoin and phenobarbital reduce sensitivity to vit. D and/or increase rate of inactivation of calcitriol. Utility: Treat nutritional rickets; prophylactic dose = 400 U/d, fully developed rickets = 3,000-4,000 U/d. Ameliorates Type I vit. D-dependent rickets (4,000 U/d). Supplement to estrogen and calcium to treat postmenopausal osteoporosis. Treat hypoparathyroidism (25-100,000 U 3x/wk + oral calcium); use calcitriol or dihydrotachysterol for faster action or if hypervit. D develops.

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Name: Vitamin D3/cholecalciferol (Delta-D) Class: Vitamin Mech.: Increases intestinal absorption of calcium and phosphate. Stimulates bone resorption by facilitating effects of PTH. Stimulates renal reabsorption of calcium and phosphate. Net result = ↑↑ calcium, ↑↑ phosphate. Absorption: Oral usu → adequate absorption. Bile is essential for absorption. Dist.: Stored in fat and muscle. Tightly bound to vitamin D-binding protein. Metab.: Requires hydroxylation in liver and kidney for full activity. Excretion, t_: 1° = bile. Weeks. Toxicity/S.E.s: Excess accumulation in fat/muscle, hypervitaminosis D, hypercalcemia. Drug interactions—phenytoin and phenobarbital reduce sensitivity to vit. D and/or increase rate of inactivation of calcitriol. Utility: Treat nutritional rickets—prophylactic dose = 400 U/d, fully developed rickets = 3,000-4,000 U/d. Ameliorates Type I vit. D-dependent rickets (4,000 U/d). Treat osteodystrophy 2° to malabsorption of vit. D and calcium—25-50,000 U 3x/wk + calcium. Supplement to estrogen and calcium to treat postmenopausal osteoporosis. Treat hypoparathyroidism (25100,000 U 3x/wk + oral calcium); use calcitriol or dihydrotachysterol for faster action or if hypervit. D develops. Special Features:

Name: Calcifediol/25-OH-cholecalciferol Class: Vitamin Mech.: Increases intestinal absorption of calcium and phosphate. Stimulates bone resorption by facilitating effects of PTH. Stimulates renal reabsorption of calcium and phosphate. Net result = ↑↑ calcium, ↑↑ phosphate. Absorption: Oral usu → adequate absorption. Bile is essential for absorption. Dist.: Stored in fat and muscle. Tightly bound to vitamin D-binding protein. Metab.: Requires hydroxylation in kidney for full activity. Excretion, t_: 1° = bile. Weeks. Toxicity/S.E.s: Excess accumulation in fat/muscle, hypervitaminosis D, hypercalcemia. Drug interactions—phenytoin and phenobarbital reduce sensitivity to vit. D and/or increase rate of inactivation of calcitriol. Utility: Treat osteomalacia 2° to liver disease. Treat renal osteodystrophy 2° to chronic renal disease—50-100 µg/d (larger dose necessary because kidney hydroxylation is deficient). Special Features: Does not require liver activation. Fully activated in kidney. More effective than calcitriol for increasing renal absorption of calcium and phosphate. Much less effective than calcitriol for increasing bone resorption and increasing intestinal reabsorption of calcium and phosphate.

Name: Calcitriol/1,25-(OH)2-cholecalciferol (Rocaltrol) Class: Vitamin Mech.: Increases intestinal absorption of calcium and phosphate. Stimulates bone resorption by facilitating effects of PTH. Stimulates renal reabsorption of calcium and phosphate. Net result = ↑↑ calcium, ↑↑ phosphate. Absorpt.: Oral usu → adequate absorption. Bile essential for absorpt. Parenteral. Dist.: Stored in fat and muscle. Tightly bound to vitamin D-binding protein. Metab.: Excretion, t_: 1° = bile. Hours. Toxicity/S.E.s: Excess accumulation in fat/muscle, hypervitaminosis D, hypercalcemia. Drug interactions—phenytoin and phenobarbital reduce sensitivity to vit. D and/or increase rate of inactivation of calcitriol. Utility: Vit. D metab. of choice for rapid action. Raises serum calcium in 1-2 d. Treat X-linked hypophosphatemic rickets (0.25-1 µg/d + phosphate salts). Treat renal osteodystrophy 2° to chronic renal disease. Ameliorates Type I vit. D-dependent rickets (0.25-0.5 µg/d). Treat hypoparathyroidism (+ calcium). Special Features: Does not require liver or kidney activation (fully activated).

Name: Dihydrotachysterol (Hytakerol, DHT) Class: Vitamin Mech.: Increases intestinal absorption of calcium and phosphate. Stimulates bone resorption by facilitating effects of PTH. Stimulates renal reabsorption of calcium and phosphate. Net result = ↑↑ calcium, ↑↑ phosphate. Absorption: Oral usu → adequate absorption. Bile is essential for absorption. Dist.: Stored in fat and muscle. Tightly bound to vitamin D-binding protein. Metab.: Requires hydroxylation in liver for full activity. Excretion, t_: 1° = bile. Toxicity/S.E.s: Excess accumulation in fat/muscle, hypervitaminosis D, hypercalcemia. Drug interactions—phenytoin and phenobarbital reduce sensitivity to vit. D and/or increase rate of inactivation of calcitriol. Utility: Treat X-linked hypophosphatemic rickets (+ phosphate salts). Treat renal osteodystrophy 2° to chronic renal disease. Treat hypoparathyroidism (+ calcium). Special Features: Does not require kidney activation. Liver hydroxylation produces full activity. _ the price of calcitriol, but takes 1-2 wk. to increase serum calcium. Serum concentration not measurable.

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Name: Synthetic parathyroid hormone (Teriparatide, Parathar) Class: Hormone Mech.: Mobilizes bone calcium by stimulating bone resorption. Increases renal absorption of calcium. Decreases renal absorption of phosphate. Increases synth. of calcitriol → ↑intest. absorption of calcium and phosphate. Net result = ↑↑calcium, ↓↓phosphate. Absorption: Dist.: Metab.: Inactivated by proteolysis. Excretion, t_: Minutes. Toxicity/S.E.s: Utility: Only used for differential diagnosis—hypoparathyroidism vs. pseudohypoparathyroidism. There is less of an increase in urinary cAMP and phosphate in pseudohypoparathyroidism. Special Features: Consists of active portion of PTH (1st 34 AAs on N-terminal). Not used to treat hypoparathyroidism. Currently being investigated for treatment of osteoporosis. Intermittent therapy → anabolic effects on bone.

Name: Sodium etidronate (Didronel) Class: Bisphosphonate Mech.: Structure sim. to inorganic pyrophosphate. Impairs formation and dissolution of calcium phosphate crystals. Alters number/activity of osteoclasts (1° effect) → slowed bone resorption. Slows formation and dissolution of hydroxyapatite crystals. Absorp.: Oral → very little absorp., but still effective. Oral absorp. varies w/dose. Further reduced by food or divalent cations. IV → much higher blood levels. Dist.: 50% of absorbed drug accum. in bone and turns over w/t_ of weeks. Metab.: Excretion, t_: 50% rapidly excreted unchanged by kidney. Toxicity/S.E.s: Protracted or high-dose therapy → osteomalacia. Utility: Treat Paget’s disease of bone as well as or better than calcitonin—oral efficacy, lower cost, no antigenicity, longer remissions. However, chronic use → osteomalacia w/↑risk of bone pain & fractures. Treat heterotopic ossification—given orally after total hip replacement or spinal injury. Treat hypercalcemia of malignancy (IV). Under testing for long-term intermittent therapy for vertebral osteoporosis (+ calcium and vit. D). Special Features: Unlike pyrophosphate, resistant to enzymatic hydrolysis. Clinical failure of therapy often due to coadmin. w/calcium tablets or food.

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Name: Human calcitonin (Cibacalcin, Calcimar) Class: Hormone Mech.: Inhibition of both bone resorption and renal tubular reabsorption of calcium and phosphate. Secretion stim by ↑ serum calcium. Net result = ↓↓calcium, ↓↓phosphate. Absorption: SC, IM. Nasal is variable and often poor. Dist.: Metab.: Inactivated by proteolysis in kidneys and blood. Excretion, t_: Minutes. Toxicity/S.E.s: Flushing of face and hands w/in min. of injxn (16-21%). Nausea/vomiting w/in 30 min. of use (14-21%); usu. diminishes w/continued therapy. Bedtime admin. can minimize effects. Urinary frequency (5-10%) Utility: Initial treatment of hypercalcemia. Diseases characterized by increased skeletal remodeling (e.g., Paget’s disease of bone). Recently approved for treatment of postmenopausal osteoporosis. Special Features: Effects begin after several hours, persist for up to 10 hr. Salmon calcitonin has a longer t_ and duration and is 50x more potent. However, 30-50% of long-term patients develop antibodies to salmon calcitonin.

Name: Pamidronate (Aredia) Class: Bisphosphonate Mech.: Structure sim. to inorganic pyrophosphate. Impairs formation and dissolution of calcium phosphate crystals. Alters number/activity of osteoclasts (1° effect) → slowed bone resorption. Slows formation and dissolution of hydroxyapatite crystals. Absorption: IV admin. only Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Utility: DOC for mod.-severe hypercalcemia assoc. w/malignant neoplasms. Treat Paget’s disease of bone. Must be used in conjnxn w/adequate hydration and urinary output. Special Features: 100x more potent than etidronate, more efficacious, and does not affect normal bone mineralization at normal therapeutic concentrations.

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Name: Alendronate (Fosamax) Class: Bisphosphonate Mech.: Structure sim. to inorganic pyrophosphate. Impairs formation and dissolution of calcium phosphate crystals. Alters number/activity of osteoclasts (1° effect) → slowed bone resorption. Slows formation and dissolution of hydroxyapatite crystals. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Utility: Increases bone mass in spines and hips of postmenopausal women → ↓ incidence of fractures. Special Features: Efficacy maintained over at least 3 yr.

Name: Plicamycin (Mithracin, nee Mithramycin) Class: Antibiotic (Cytotoxic) Mech.: Intercalates into DNA like actinomycin and blocks DNA, RNA, and protein synthesis. Supposedly decreases serum calcium levels by direct toxic action on osteoclasts. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Less severe w/doses for hypercalcemia than for neoplasms. Sudden onset of thrombocytopenia followed by hemorrhage. Hepatic and renal toxicity. Hypocalcemia. Monitor platelet count, liver/kidney fxn, and serum calcium. C/i for patients w/renal or hepatic disease, bone marrow disease, thrombocytopathy, coagulation disorders, or bleeding susceptibilities of other etiologies. Utility: Treat severe hypercalcemia resulting from CA w/wo bony metastases. Treat testicular neoplasms. Special Features: Use limited by toxicity.

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Name: Prednisone Class: Corticosteroid (Glucocorticoid) Mech.: ↑ PMNs in periph. blood, but decrease all other WBCs. Inhib. monocyte reactivity and secretion of IL-1 & TNF. Inhib. T cell activation, IgE-med. rxns, inducible cyclooxygenase II expression. Induces lipocortin → inhibition of phospholipase A2. Absorption: IV, IM, oral. Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Cataracts, hypertension, osteoporosis, myopathy, obesity, acne, hirsutism, hyperglycemia, muscle atrophy/myopathy, convulsions, mood changes, derm. changes, ↓ cellular immunity. Glucocorticoid admin > equiv. of 20 mg hydrocortisone/d → suppression of HPA axis. Sudden stop of chronic therapy → impaired physiologic homeostasis. Drug Interactions—phenytoin, barbiturates, & rifampin induce catabolic enzymes; antacids → ↓ bioavailability of prednisone; salicylate levels reduced; increased doses required for insulin, hypoglycemic agents, antihypertensives, and glaucoma meds; if hypokalemia occurs, increased toxicity of digoxin. Utility: Oral for asthma. Immunosuppression, anti-inflammatory actions, cytostatic actions against some lymphocyte tumors, mgt. of allergic diseases. Special Features: Synth. agents have potent anti-inflamm. activity w/little (if any) mineralocorticoid effect.

Name: Hydrocortisone/Cortisol Class: Corticosteroid (Glucocorticoid) Mech.: ↑ PMNs in periph. blood, but decrease all other WBCs. Inhib. monocyte reactivity and secretion of IL-1 & TNF. Inhib. T cell activation, IgE-med. rxns, inducible cyclooxygenase II expression. Induces lipocortin → inhibition of phospholipase A2. Absorption: IV, IM, oral, topical. Dist.: Metab.: Excretion, t_: 8-12 hr. Toxicity/S.E.s: Cataracts, hypertension, osteoporosis, myopathy, obesity, acne, hirsutism, hyperglycemia, muscle atrophy/myopathy, convulsions, mood changes, derm. changes, ↓ cellular immunity. Glucocorticoid admin > equiv. of 20 mg hydrocortisone/d → suppression of HPA axis. Sudden stop of chronic therapy → impaired physiologic homeostasis. Drug Interactions—phenytoin, barbiturates, & rifampin induce catabolic enzymes; antacids → ↓ bioavailability of prednisone; salicylate levels reduced; increased doses required for insulin, hypoglycemic agents, antihypertensives, and glaucoma meds; if hypokalemia occurs, increased toxicity of digoxin. Utility: IV/IM for asthma. Immunosuppression, anti-inflammatory actions, cytostatic actions against some lymphocyte tumors, mgt. of allergic diseases. Special Features: Rel. anti-inflamm potency = 1. Synth. agents have potent anti-inflamm. activity w/little (if any) mineralocorticoid effect.

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Name: Beclomethasone diproprionate (Beclovent) Class: Corticosteroid (Glucocorticoid) Mech.: ↑ PMNs in periph. blood, but decrease all other WBCs. Inhib. monocyte reactivity and secretion of IL-1 & TNF. Inhib. T cell activation, IgE-med. rxns, inducible cyclooxygenase II expression. Induces lipocortin → inhibition of phospholipase A2. Absorption: Aerosol, nasal pump spray, oral, topical. Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Cataracts, hypertension, osteoporosis, myopathy, obesity, acne, hirsutism, hyperglycemia, muscle atrophy/myopathy, convulsions, mood changes, derm. changes, ↓ cellular immunity. Glucocorticoid admin > equiv. of 20 mg hydrocortisone/d → suppression of HPA axis. Sudden stop of chronic therapy → impaired physiologic homeostasis. Drug Interactions—phenytoin, barbiturates, & rifampin induce catabolic enzymes; antacids → ↓ bioavailability of prednisone; salicylate levels reduced; increased doses required for insulin, hypoglycemic agents, antihypertensives, and glaucoma meds; if hypokalemia occurs, increased toxicity of digoxin. Aerosol—oral candidiasis, dysphonia. Utility: Asthma, allergic rhinitis. Immunosuppression, anti-inflammatory actions, cytostatic actions against some lymphocyte tumors, mgt. of allergic diseases. Special Features: Synth. agents have potent anti-inflamm. activity w/little (if any) mineralocorticoid effect.

Name: Triamcinolone acetonide (Azmacort) Class: Corticosteroid (Glucocorticoid) Mech.: ↑ PMNs in periph. blood, but decrease all other WBCs. Inhib. monocyte reactivity and secretion of IL-1 & TNF. Inhib. T cell activation, IgE-med. rxns, inducible cyclooxygenase II expression. Induces lipocortin → inhibition of phospholipase A2. Absorption: IM, aerosol, oral, topical, intraarticular. Dist.: Metab.: Excretion, t_: 12-36 hr. Toxicity/S.E.s: Cataracts, hypertension, osteoporosis, myopathy, obesity, acne, hirsutism, hyperglycemia, muscle atrophy/myopathy, convulsions, mood changes, derm. changes, ↓ cellular immunity. Glucocorticoid admin > equiv. of 20 mg hydrocortisone/d → suppression of HPA axis. Sudden stop of chronic therapy → impaired physiologic homeostasis. Drug Interactions—phenytoin, barbiturates, & rifampin induce catabolic enzymes; antacids → ↓ bioavailability of prednisone; salicylate levels reduced; increased doses required for insulin, hypoglycemic agents, antihypertensives, and glaucoma meds; if hypokalemia occurs, increased toxicity of digoxin. Aerosol—oral candidiasis, dysphonia. Utility: Asthma. Intraarticular injxn. to reduce inflamm. Immunosuppression, anti-inflammatory actions, cytostatic actions against some lymphocyte tumors, mgt. of allergic diseases. Special Features: Rel. anti-inflamm. potency of 5. Synth. agents have potent anti-inflamm. activity w/little (if any) mineralocorticoid effect.

Name: Dexamethasone (Decadron) Class: Corticosteroid (Glucocorticoid) Mech.: ↑ PMNs in periph. blood, but decrease all other WBCs. Inhib. monocyte reactivity and secretion of IL-1 & TNF. Inhib. T cell activation, IgE-med. rxns, inducible cyclooxygenase II expression. Induces lipocortin → inhibition of phospholipase A2. Absorption: IV, IM, Oral, topical, intraarticular. Dist.: Metab.: Excretion, t_: 36-72 hr. Toxicity/S.E.s: Cataracts, hypertension, osteoporosis, myopathy, obesity, acne, hirsutism, hyperglycemia, muscle atrophy/myopathy, convulsions, mood changes, derm. changes, ↓ cellular immunity. Glucocorticoid admin > equiv. of 20 mg hydrocortisone/d → suppression of HPA axis. Sudden stop of chronic therapy → impaired physiologic homeostasis. Drug Interactions—phenytoin, barbiturates, & rifampin induce catabolic enzymes; antacids → ↓ bioavailability of prednisone; salicylate levels reduced; increased doses required for insulin, hypoglycemic agents, antihypertensives, and glaucoma meds; if hypokalemia occurs, increased toxicity of digoxin. Utility: Intraarticular injxn. to reduce inflamm. Immunosuppression, anti-inflammatory actions, cytostatic actions against some lymphocyte tumors, mgt. of allergic diseases. Special Features: Rel. anti-inflamm. potency of 20-30. Synth. agents have potent anti-inflamm. activity w/little (if any) mineralocorticoid effect.

Name: Regular insulin Class: Insulin (Fast-Acting Insulin Injection)

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Mech.: Interacts w/ insulin receptors on cell membranes → phosph/dephosph of enzymes→ glucose transport into cells (esp. fat & muscle), glycogen synth., ↓ FFA, ↑ triglyceride storage, K+ & Mg2+ uptake, protein synth. Regulation of cell proliferation & differentiation. May activate cAMP (significance unknown). Absorption: Injection (usu. SC). Dist.: Metab.: Rapidly metab. by liver, kidneys, and muscle. Excretion, t_: 5-6 min. Toxicity/S.E.s: Most freq. = hypoglycemia → ANS hyperactivity, impaired CNS fxn (confusion, bizarre behavior, coma). Skin rxns—transient urticaria, subcut. fibrosis, localized atrophy of subcut. tissue. Allergic rxn. Insulin resistance—refractory receptors or anti-insulin antibodies (may require 2001000 units/d). Utility: Treat diabetes mellitus. Preprandial control of blood glucose. Special Features: Rapid onset (0.5-1 hr). Short duration (5-8 hr). Amorphous.

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Name: Isophane insulin suspension (NPH insulin) Class: Insulin (Intermediate-Acting Suspension)

Name: Insulin Zn (Lente insulin) Class: Insulin (Intermediate-Acting Suspension)

Mech.: Interacts w/ insulin receptors on cell membranes → phosph/dephosph of enzymes → glucose transport into cells (esp. fat & muscle), glycogen synth., ↓ FFA, ↑ triglyceride storage, K+ & Mg2+ uptake, protein synth. Regulation of cell proliferation & differentiation. May activate cAMP (significance unknown). Absorption: Injection (usu. SC). Dist.: Metab.: Rapidly metab. by liver, kidneys, and muscle. Excretion, t_: 5-6 min.

Mech.: Interacts w/ insulin receptors on cell membranes → phosph/dephosph of enzymes → glucose transport into cells (esp. fat & muscle), glycogen synth., ↓ FFA, ↑ triglyceride storage, K+ & Mg2+ uptake, protein synth. Regulation of cell proliferation & differentiation. May activate cAMP (significance unknown). Absorption: Injection (usu. SC). Metab.: Rapidly metab. by liver, kidneys, and muscle. Excretion, t_: 5-6 min.

Toxicity/S.E.s: Most freq. = hypoglycemia → ANS hyperactivity, impaired CNS fxn (confusion, bizarre behavior, coma). Skin rxns—transient urticaria, subcut. fibrosis, localized atrophy of subcut. tissue. Allergic rxn. Insulin resistance—refractory receptors or anti-insulin antibodies (may require 2001000 units/d). Utility: Treat diabetes mellitus. Basal control of blood glucose. Special Features: Equal concentrations of insulin and protamine. Intermediate duration (24 hr). Name: Extended insulin zinc suspension (Ultralente insulin) Class: Insulin (Long-Acting) Mech.: Interacts w/ insulin receptors on cell membranes → phosph/dephosph of enzymes → glucose transport into cells (esp. fat & muscle), glycogen synth., ↓ FFA, ↑ triglyceride storage, K+ & Mg2+ uptake, protein synth. Regulation of cell proliferation & differentiation. May activate cAMP (significance unknown). Absorption: Injection (usu. SC). Metab.: Rapidly metab. by liver, kidneys, and muscle. Excretion, t_: 5-6 min. Toxicity/S.E.s: Most freq. = hypoglycemia → ANS hyperactivity, impaired CNS fxn (confusion, bizarre behavior, coma). Skin rxns—transient urticaria, subcut. fibrosis, localized atrophy of subcut. tissue. Allergic rxn. Insulin resistance—refractory receptors or anti-insulin antibodies (may require 2001000 units/d). Utility: Treat diabetes mellitus. Basal control of blood glucose.

Toxicity/S.E.s: Most freq. = hypoglycemia → ANS hyperactivity, impaired CNS fxn (confusion, bizarre behavior, coma). Skin rxns—transient urticaria, subcut. fibrosis, localized atrophy of subcut. tissue. Allergic rxn. Insulin resistance—refractory receptors or anti-insulin antibodies (may require 2001000 units/d). Utility: Treat diabetes mellitus. Basal control of blood glucose. Special Features: 70% crystalline form (ultralente) + 30% amorphous form (semilente) of Zn-insulin complex. Zn forms rel. insoluble complex w/insulin → slow absorption. Name: Tolbutamide (Orinase) Class: Anti-Diabetes Agent (Oral Hypoglycemic) (Sulfonylurea) (First Generation) Mech.: Interferes w/ATP-sensitive K+ channel. Reduced K+ conductance → depolarization & influx of Ca2+. Stim. of insulin release from pancreas, ↓ glucagon, ↑ binding of insulin to target tissue receptors. Absorption: Oral. Dist.: Largely bound to plasma proteins. Metab.: Hepatic. Excretion, t_: Short duration of action (~8 hr). Toxicity/S.E.s: Severe side effects in 2-4%. Only 10% still use them after 6-9 yrs of treatment. Sustained hypoglycemia up to 4-5 days after discontinued use. Rash (rare), GI upset (3-4%), hematological disturbance—usu. leukopenia (1%), inappropriate ADH release (→ hyponatremia), flushing, disulfiram action, variability in steady state conc. Drug interactions—protein binding (alcohol, β blockers, MAO inhibitors). Utility: NIDDM—prevents acute hyperglycemic problems, may postpone development of glucose intolerance, may delay thickening of capillary BM. Special Features:

Special Features: Crystalline form of Zn-insulin complex—very insoluble → slow absorption.

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Name: Chlorpropramide (Diabinese) Class: Anti-Diabetes Agent (Oral Hypoglycemic) (Sulfonylurea) (First Generation) Mech.: Interferes w/ATP-sensitive K+ channel. Reduced K+ conductance → depolarization & influx of Ca2+. Stim. of insulin release from pancreas, ↓ glucagon, ↑ binding of insulin to target tissue receptors. Absorption: Oral. Dist.: Largely bound to plasma proteins. Metab.: Hepatic. Excretion, t_: Long duration of action (36+ hr). Toxicity/S.E.s: Severe side effects in 2-4%. Only 10% still use them after 6-9 yrs of treatment. Sustained hypoglycemia (esp. likely) up to 4-5 days after discont. use. Rash (rare), GI upset (3-4%), hematological disturbance—usu. leukopenia (1%), inappropriate ADH release (→ hyponatremia), flushing, disulfiram action (highest incidence of the class), variability in steady state conc. C/i in the elderly. Drug interactions—protein binding (alcohol, β blockers, MAO inhibitors). Utility: NIDDM—prevents acute hyperglycemic problems, may postpone development of glucose intolerance, may delay thickening of capillary BM. Special Features: Highest incidence of S.E.’s in sulfonylurea group.

Name: Glyburide (Micronase) Class: Anti-Diabetes Agent (Oral Hypoglycemic) (Sulfonylurea) (Second Gen.) Mech.: Interferes w/ATP-sensitive K+ channel. Reduced K+ conductance → depolarization & influx of Ca2+. Stim. of insulin release from pancreas, ↓ glucagon, ↑ binding of insulin to target tissue receptors. Absorption: Oral. Dist.: Largely bound to plasma proteins. Metab.: Hepatic. Excret., t_: Intermed. duration of action (t_=1.5-5 hr), but duration of effect 24 hr. Toxicity/S.E.s: Severe side effects in 2-4%. Only 10% still use them after 6-9 yrs of treatment. Sustained hypoglycemia up to 4-5 days after discontinued use. Rash (rare), GI upset (3-4%), hematological disturbance—usu. leukopenia (1%), inappropriate ADH release (→ hyponatremia), flushing, disulfiram action, variability in steady state conc. Drug interactions—protein binding (alcohol, β blockers, MAO inhibitors)l. Utility: NIDDM—prevents acute hyperglycemic problems, may postpone development of glucose intolerance, may delay thickening of capillary BM. Special Features: More lipophilic and 100x more potent than first gen.

Name: Glipizide (Glucotrol) Class: Anti-Diabetes Agent (Oral Hypoglycemic) (Sulfonylurea) (Second Gen.) Mech.: Interferes w/ATP-sensitive K+ channel. Reduced K+ conductance → depolarization & influx of Ca2+. Stim. of insulin release from pancreas, ↓ glucagon, ↑ binding of insulin to target tissue receptors. Absorption: Oral. Dist.: Largely bound to plasma proteins. Metab.: Hepatic. Excret., t_: Intermed. duration of action (t_=1.5-5 hr), but duration of effect 18 hr. Toxicity/S.E.s: Severe side effects in 2-4%. Only 10% still use them after 6-9 yrs of treatment. Sustained hypoglycemia up to 4-5 days after discontinued use. Rash (rare), GI upset (3-4%), hematological disturbance—usu. leukopenia (1%), inappropriate ADH release (→ hyponatremia), flushing, disulfiram action, variability in steady state conc. Drug interactions—protein binding (alcohol, β blockers, MAO inhibitors)l. Utility: NIDDM—prevents acute hyperglycemic problems, may postpone development of glucose intolerance, may delay thickening of capillary BM. Special Features: More lipophilic and 100x more potent than first gen.

Name: Metformin (Glucophage) Class: Anti-Diabetes Agent (Oral Hypoglycemic) (Biguanide)

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Mech.: Decreases hepatic output → decreased plasma glucose. Does not directly stimulate insulin production. Absorption: Oral → good absorption. Dist.: No protein binding. Metab.: Excretion, t_: Excreted unmetabolized in urine. 8 hr. Toxicity/S.E.s: Lactic acidosis (1:40,000-80,000), metallic aftertaste, nausea, diarrhea. May reduce triglycerides. Utility: Use alone or in combination w/sulfonylureas to treat NIDDM that doesn’t respond well to sulfonylureas alone. Special Features: Only reduces blood glucose in the presence of hyperglycemia. Has not been found to cause serious hypoglycemia.

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Name: Acarbose (Precose) Class: Anti-Diabetes Agent (Oral Hypoglycemic)

Name: Troglitazone Class: Anti-Diabetes Agent (Oral Hypoglycemic)

Mech.: Inhibits α-glucosidase → ↓ conversion of carbohydrates to glucose in the small intestine → ↓ absorption of glucose → ↓ post-prandial glucose rise. Does not stimulate insulin release or action. ∴ No hypoglycemia.

Mech.: ↑ glucose utilization and reduces production by ↑ receptor response to insulin. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Utility: May help prevent development of NIDDM. Special Features:

Absorption: Oral → poor absorption. Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Flatulence, diarrhea, abdominal cramping. Utility: Treat NIDDM. Possible adjunct to insulin for IDDM. Special Features:

Name: Thiazides Class: Diuretic Mech.: ↓ reabsorption of Na+ in distal tubule by inhibition of a Na+ /Clcotransporter on the luminal membrane. Promotes reabsorption of Ca2+ → ↓ Ca2+ in urine. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Potassium depletion, hyperuricemia, volume depletion, hypercalcemia, hyperglycemia, hypersensitivity. Utility: Treat hypertension, congestive heart failure, renal impairment, hypercalciuria, diabetes insipidus. Special Features:

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Name: Furosemide (Lasix) Class: Loop Diuretic Mech.: Inhib. Na+ /K+ /Cl- cotransport of the luminal membrane in the ascending limb of the loop of Henle → ↓ reabsorption of Na+ , K+ , & Cl-. Increases conc. of Ca2+ in urine. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Ototoxicity, hyperuricemia, acute hypovolemia, potassium depletion. Utility: DOC for reducing acute pulmonary edema of congestive heart failure. Rapid onset, so useful in emergency situations. Treat hypercalcemia. Special Features:

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Pharmacology GI – Cards

Name: Cimetidine (Tagamet) Class: H2 Receptor Antagonist Mech.: Competitive inhib. of the histamine H2 receptor, but not of the H1 receptor → inhib. of fasting and stim. acid secretion. No disruption of circadian rhythm of acid secretion. Inhib. of 80-90% of gastrin and vagal-stim. acid secretion. Absorption: Oral → rapid, good absorption. Single nighttime dose. Dist.: Metab.: Partial hepatic metab. Excretion, t_: Excreted intact in urine. 1.5-3 hr. Toxicity/S.E.s: Uncommon. Diarrhea, headaches, myalgias, skin rashes. Large doses over prolonged periods assoc. w/impotence & gynecomastia. Inhib. cyt. P-450 → dose adjustment with phenytoin, warfarin, & theophylline. Occasional cardiac arrhythmias. Utility: PUD, Zollinger-Ellison synd., acute stress ulcers, GERD Special Features: Potency—famotidine > ranitidine/nizatidine > cimetidine. Tachyphylaxis—50% less effective after 6 months. Rebound hypersecretion 2° to receptor upregulation and inhib. of ATPase recycling.

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Name: Ranitidine (Zantac) Class: H2 Receptor Antagonist Mech.: Competitive inhib. of the histamine H2 receptor, but not of the H1 receptor → inhib. of fasting and stim. acid secretion. No disruption of circadian rhythm of acid secretion. Inhib. of 80-90% of gastrin and vagal-stim. acid secretion. Absorption: Oral → rapid, good absorption. Single nighttime dose. Dist.: Metab.: Partial hepatic metab. Excretion, t_: Excreted intact in urine. 1.5-3 hr. Toxicity/S.E.s: Uncommon. Diarrhea, headaches, myalgias, skin rashes. Inhib. cyt. P-450 (less than cimetidine) → dose adjustment with phenytoin, warfarin, & theophylline. Occasional cardiac arrhythmias. Utility: PUD, Zollinger-Ellison synd., acute stress ulcers, GERD Special Features: Potency—famotidine > ranitidine/nizatidine > cimetidine. Tachyphylaxis—50% less effective after 6 months. Rebound hypersecretion 2° to receptor upregulation and inhib. of ATPase recycling.

Name: Nizatidine (Axid) Class: H2 Receptor Antagonist Mech.: Competitive inhib. of the histamine H2 receptor, but not of the H1 receptor → inhib. of fasting and stim. acid secretion. No disruption of circadian rhythm of acid secretion. Inhib. of 80-90% of gastrin and vagal-stim. acid secretion. Absorption: Oral → rapid, good absorption. Single nighttime dose. Dist.: Metab.: Partial hepatic metab. Excretion, t_: Excreted intact in urine. 1.5-3 hr. Toxicity/S.E.s: Uncommon. Diarrhea, headaches, myalgias, skin rashes. Occasional cardiac arrhythmias. Utility: PUD, Zollinger-Ellison synd., acute stress ulcers, GERD Special Features: Potency—famotidine > ranitidine/nizatidine > cimetidine. Tachyphylaxis—50% less effective after 6 months. Rebound hypersecretion 2° to receptor upregulation and inhib. of ATPase recycling.

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Name: Famotidine (Pepcid) Class: H2 Receptor Antagonist Mech.: Competitive inhib. of the histamine H2 receptor, but not of the H1 receptor → inhib. of fasting and stim. acid secretion. No disruption of circadian rhythm of acid secretion. Inhib. of 80-90% of gastrin and vagal-stim. acid secretion. Absorption: Oral → rapid, good absorption. Single nighttime dose. Dist.: Metab.: Partial hepatic metab. Excretion, t_: Excreted intact in urine. 1.5-3 hr. Toxicity/S.E.s: Uncommon. Diarrhea, headaches, myalgias, skin rashes. Occasional cardiac arrhythmias (more common than in other H2RAs). Utility: PUD, Zollinger-Ellison synd., acute stress ulcers, GERD Special Features: Potency—famotidine > ranitidine/nizatidine > cimetidine. Tachyphylaxis—50% less effective after 6 months. Rebound hypersecretion 2° to receptor upregulation and inhib. of ATPase recycling.

Name: Aluminum Hydroxide (Maalox) Class: Antacid

Name: Omeprazole (Prilosec) Class: Proton Pump Inhibitor

Name: Al-Mg Hydroxides Class: Antacid

Mech.: Irreversible inhib. of H+ /K+ ATPase → > 95% inhib. of acid secretion.

Mech.: Weak base → ↓ gastric acidity. ↑ pH → ↓ peptic activity.

Absorption: Oral → 30-40% bioavail. Peak plasma levels at 0.5-3.5 hr. Give prior to meals, preferably in the morning. Additional dose, if necessary, should be given later in the day. Dist.: Metab.: Excretion, t_: 0.5-1 hr. Toxicity/S.E.s: Rare headache, diarrhea, rash. Inhib. of cyt. P-450 requires altered doses of warfarin, phenytoin, diazepam, and cyclosporin. Inhib. of vitamin. B12 absorption. Utility: PUD, erosive esophagitis, Zollinger-Ellison synd., GERD. Special Features: Mismatch between pharmacokinetics & pharmacodynamics. Short t_, but actions last > 24 hr (irreversible binding). Acid inhib. → ↑ gastrin.

Absorption: Dist.: Metab.: Excretion, t_:

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Mech.: Weak base → ↓ gastric acidity. ↑ pH → ↓ peptic activity. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Constipation. Al3+ can form insoluble complexes w/other drugs → ↓ absorption (e.g., tetracycline). Utility: PUD Special Features:

Toxicity/S.E.s: Al3+ can form insoluble complexes w/other drugs → ↓ absorption (e.g., tetracycline). Utility: PUD Special Features: Comb. of constipation (Al) and laxative (Mg) effects may cancel → rel. normal bowel function.

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Name: Magnesium Hydroxide (Milk of Magnesia) Class: Antacid Mech.: Weak base → ↓ gastric acidity. ↑ pH → ↓ peptic activity. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Diarrhea. Utility: PUD Special Features:

Name: Misoprostol (Cytotec) Class: Prostaglandin Analogue (PGE1) Mech.: Stim. mucus and bicarbonate secretion, mucosal blood flow, cell turnover. Inhib. acid secretion. Absorption: Dist.: Metab.: Excretion, t_: Longer t_ than natural prostaglandins. Toxicity/S.E.s: ↑ intest. secretion → diarrhea. Nausea. Uterine contractions. ∴ c/i during pregnancy. Utility: PUD, prevention of NSAID injury. Special Features:

Name: Calcium Carbonate (Tums, Rolaids) Class: Antacid

Name: Bismuth-Subsalicylate (Pepto-Bismol) Class: Cytoprotective Agent/Hydrophilic Agent/Absorbent/Antimicrobial.

Mech.: Weak base → ↓ gastric acidity. ↑ pH → ↓ peptic activity.

Mech.: Inhib. pepsin activity, ↑ mucus secretion, coats & protects ulcer. Antimicrobial action. May have antiinflammatory action. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Binds tetracyclines. Turns stools and tongue black. Contains salicylate → additive effects w/aspirin, tinnitus. Don’t use w/salicylate allergy. May cause GI impaction in debilitated patients. Utility: PUD. Traveler’s Diarrhea (at least in Mexico)—8 doses (1-2 tablets every eight hours). Prophylaxis for Traveler’s Diarrhea. General diarrhea (usu. controls diarrhea w/in 24 hr). Special Features:

Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Utility: PUD Special Features: Counterproductive—Ca2+ stimulates gastrin release.

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Name: Sucralfate (Carafate) Class: Cytoprotective Agent Mech.: Complex of aluminum hydroxide and sulfated sucrose. Forms complex gels w/mucus → physical barrier than impairs diffusion of HCl and prevents peptic mucus degradation. Stim. prostaglandin release and secretion of mucus and bicarbonate. Inhib. acid secretion by ~50%. Absorption: Not absorbed. Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Well tolerated. Utility: PUD Special Features: Largely supplanted by H2RAs and PPIs. Requires acidic pH for activation. ∴ should not be admin. w/antacids, PPIs, or H2RAs.

Name: Metronidazole (Flagyl) Class: Nitroimidazole derivative Mech.: Inhib. DNA synth, degrades DNA, e- acceptor for reduced substrates. Absorption: Complete, quick oral absorption. Dist.: Well distrib to all tissues and fluids (including CSF) Metab.: Hepatic metab. Excretion, t_: Toxicity/S.E.s: GI, metallic taste, neurotox (vertigo), disulfiram-like effect w/alcohol, neutropenia. Not for first trimester preg (mutagenic). Not for patients w/active CNS disease or hist. of blood dyscrasias. Utility: IV treatment of anaerobic infects. Oral for amebiasis, giardiasis, and genital infects of Trichomonas vaginalis. H. pylori (PUD). Special Features: Antiparasitic and antibacterial activity. All anaerobic cocci and anaerobic gram- bacilli, including Bacterioides. Trichomoniasis, amebiasis, giardiasis.

Name: Pirenzipene Class: -Muscarinic Antagonist

Name: Amoxicillin (Amoxil) Class: Penicillin (Aminopenicillin) Mech.: Binds to PBPs, blocks activity of transpeptidases in terminal stages of cell wall formation. Bactericidal. Absorption: Acid stable. Good oral (better than ampicillin). Distrib.: Widely distributed, little CSF unless meninges inflamed. Metab.: Excretion, t_: Rapidly elim. by kidneys (probenecid blocks excretion), small amt. in bile. Toxicity/S.E.s: diarrhea (less than ampicillin), hypersensitivity (1-10%), superinfection. Utility: More effective against gram -s (esp. Proteus, H. influenzae, E. coli, P. mirabilis). Less active than Pen. G against gram+ cocci. H. pylori (PUD). Special Features: Broad spectrum.

Mech.: M1-inhib. → suppression of gastrin-stimulated and basal acid secretion at doses that have a minimal effect on salivary glands, heart, and eyes. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Utility: PUD. Special Features:

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Name: Tetracycline (Achromycin V) Class: Tetracycline Mech.: Active uptake into bacteria →inhib protein synth by binding to 30S ribosome. Bacteriostatic Absorption: Oral adequate, but incomplete. Impaired by divalent cations. IM painful. IV may cause thrombophlebitis. Never intrathecal. Distrib.: Good CSF. Conc. in liver → enterohepatic circ. Penetrates most tissues and fluids. Crosses placenta. Metab.: Excretion, t_: filtration (1°), bile Toxicity/S.E.s: GI — burning, discomfort, nausea, vomiting; superinfection — due to broad spectrum, candida albicans (1°), staph enterocolitis, pseudomemb. colitis; hepatotoxicity (esp. in pregnancy); renal toxicity; Fanconi synd.; perm. brown discoloration of teeth; slowing of bone growth; phototoxicity; thrombophlebitis; hematopoetic changes; rare hypersens. rxns.

Utility: gram - cocci, gram - bacilli, acid fast bacilli, chlamydiae, mycoplasma, rickettsia, spirochetes. No effect on viruses or fungi. Also used for acne, prophylaxis for Travelers’ diarrhea. H. pylori (PUD). Special Features: Broad spectrum. Decreased effect of oral contraceptives.

Name: Methylcellulose Class: Laxative (Bulk-Forming Agent) Mech.: Absorbs and retains water, increases fecal volume → ↑ rate of transit. Absorption: Not absorbed. Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Can bind other drugs → reduced absorption. Admin. > 1 hr before or after other medication. Utility: Laxative. Esp. useful in pts. w/alternating constipation and diarrhea (e.g., irritable bowel synd) → ↓ fluidity of liquid stools and softening of hard stools. Also useful for pts who are on low residue diets; are postpartum; are elderly; or have diverticular disease, spastic colon, or hemorrhoids. Special Features: Inert, hydrophilic. Introduce gradually to avoid GI impaction. Gentle agent. Requires 1/2-3 days for effect.

Name: Psyllium (Metamucil) Class: Laxative (Bulk-Forming Agent)

Name: Magnesium Sulfate Class: Laxative (Saline Cathartic)

Mech.: Absorbs and retains water, increases fecal volume → ↑ rate of transit.

Mech.: Nonabsorbable ions→ ↑ osmotic pressure in bowel → watery stools in 1-3 hr. Absorption: Not much. Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Toxic levels of Mg2+ may accumulate in infants, old folk, and pts. w/impaired renal fxn. Large amount of Na+ (prob. for pts. on low Na+ diets). Potential problem of dehydration. Utility: Acute evacuation of bowel in preparation for endoscopic exam. Elim. of drugs/toxins for suspected drug/food poisoning. Special Features:

Absorption: Not absorbed. Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Can bind other drugs → reduced absorption. Admin. > 1 hr before or after other medication. Utility: Laxative. Esp. useful in pts. w/alternating constipation and diarrhea (e.g., irritable bowel synd) → ↓ fluidity of liquid stools and softening of hard stools. Also useful for pts who are on low residue diets; are postpartum; are elderly; or have diverticular disease, spastic colon, or hemorrhoids. Special Features: Inert, hydrophilic. Introduce gradually to avoid GI impaction. Gentle agent. Requires 1/2-3 days for effect.

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Name: Polycarbophil Class: Laxative (Bulk-Forming Agent) Mech.: Absorbs and retains water, increases fecal volume → ↑ rate of transit. Absorption: Not absorbed. Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Can bind other drugs → reduced absorption. Admin. > 1 hr before or after other medication. Utility: Laxative. Esp. useful in pts. w/alternating constipation and diarrhea (e.g., irritable bowel synd) → ↓ fluidity of liquid stools and softening of hard stools. Also useful for pts who are on low residue diets; are postpartum; are elderly; or have diverticular disease, spastic colon, or hemorrhoids. Special Features: Inert, hydrophilic. Introduce gradually to avoid GI impaction. Gentle agent. Requires 1/2-3 days for effect.

And this is the Noble Truth of Sorrow. Birth is sorrow, age is sorrow, disease is sorrow, death is sorrow; contact with the unpleasant is sorrow, separation from the pleasant is sorrow, every wish unfulfilled is sorrow—in short all the five components of individuality are sorrow. And this is the Noble Truth of the Arising of Sorrow. It arises from craving, which leads to rebirth, which brings delight and passion, and seeks pleasure now here, now there—the craving for sensual pleasure, the craving for continued life, the craving for power. And this is the Noble Truth of the Stopping of Sorrow. It is the complete stopping of that craving, so that no passion remains, leaving it, being emancipated from it, being released from it, giving no place to it. And this is the Noble Truth of the Way to the Stopping of Sorrow. It is the Noble Eightfold Path—Right Views, Right Resolve, Right Speech, Right Conduct, Right Livelihood, Right Effort, Right Mindfulness, and Right Concentration. —The Buddha

Name: Magnesium Hydroxide Class: Laxative (Saline Cathartic)

Name: Magnesium Citrate Class: Laxative (Saline Cathartic)

Mech.: Nonabsorbable ions → ↑ osmotic pressure in bowel → watery stools in 1-3 hr. Absorption: Not much. Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Toxic levels of Mg2+ may accumulate in infants, old folk, and pts. w/impaired renal fxn. Large amount of Na+ (prob. for pts. on low Na+ diets). Potential problem of dehydration. Utility: Acute evacuation of bowel in preparation for endoscopic exam. Elim. of drugs/toxins for suspected drug/food poisoning. Special Features:

Mech.: Nonabsorbable ions→ ↑ osmotic pressure in bowel → watery stools in 1-3 hr. Absorption: Not much. Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Toxic levels of Mg2+ may accumulate in infants, old folk, and pts. w/impaired renal fxn. Large amount of Na+ (prob. for pts. on low Na+ diets). Potential problem of dehydration. Utility: Acute evacuation of bowel in preparation for endoscopic exam. Elim. of drugs/toxins for suspected drug/food poisoning. Special Features:

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Name: Sodium Phosphate Class: Laxative (Saline Cathartic)

Name: Phenolphthalein (Ex-Lax) Class: Laxative (Contact Cathartic) (Diphenylmethane Cathartic)

Mech.: Nonabsorbable ions → ↑ osmotic pressure in bowel → watery stools in 1-3 hr. Absorption: Not much. Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Large amount of Na+ (prob. for pts. on low Na+ diets). Potential problem of dehydration. Utility: Acute evacuation of bowel in preparation for endoscopic exam. Elim. of drugs/toxins for suspected drug/food poisoning. Special Features:

Mech.: Act on colon → ↑ peristalsis. Effects take at least 6 hr. to manifest.

Name: Bisacodyl (Dulcolax) Class: Laxative (Contact Cathartic) (Diphenylmethane Cathartic)

Name: Bisacodyl Tannex (Clysodrast) Class: Laxative (Contact Cathartic) (Diphenylmethane Cathartic)

Mech.: Act on colon → ↑ peristalsis. Effects take at least 6 hr. to manifest.

Mech.: Act on colon → ↑ peristalsis.

Absorption: Oral → 5% absorption. Enema, suppositories (can be irritating).

Absorption: Enema. Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Fluid and electrolyte depletion, abdominal cramping, metabolic acidosis or alkalosis, hypocalcemia, tetany. Tannic acid in large amounts is hepatotoxic. Use caution w/multiple enemas. Don’t use in pts. w/colonic ulcers or in kids < 10 y.o. Don’t use > 7.5 g at a time or > 10 g over 72 hr. Utility: Preparation of colon for surgery or X-ray.

Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Fluid and electrolyte depletion, abdominal cramping, metabolic acidosis or alkalosis, hypocalcemia, tetany. Potential for atonic colon w/prolonged use. Utility: Preparation of colon for surgery or X-ray. Special Features: Most useful contact cathartic. Indiv. effective doses vary 48x. Acid/base indicator → pink/red urine. Contact cathartics are most commonly involved in prolonged cathartic abuse. Should never be used > 1 wk of regular therapy. Not recommended for initial therapy.

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Absorption: Oral → 15% absorption Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Fluid and electrolyte depletion, abdominal cramping, ashes, osteomalacia. Potential for atonic colon w/prolonged use. Utility: Laxative. Special Features: Indiv. effective doses vary 4-8x. Acid/base indicator → pink/red urine. Not effective in pts. who lack bile. Contact cathartics are most commonly involved in prolonged cathartic abuse. Should never be used > 1 wk of regular therapy. Not recommended for initial therapy.

Special Features: Indiv. effective doses vary 4-8x. Acid/base indicator → pink/red urine.

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Name: Anthraquinones (senna, cascara, danthron, aloe) Class: Laxative (Contact Cathartic) (Anthraquinone Cathartic) Mech.: Emodin, an anthraquinone, stimulates peristalsis in the colon. Effects take > 6 hr. to develop. Absorption: Dist.: Breast milk. Metab.: Excretion, t_: Partial kidney excretion (may color urine). Toxicity/S.E.s: Excessive catharsis. Colored urine. Not to be used by nursing mothers. Utility: Laxative Special Features: Activated by intestinal microflora. More complete evacuation than diphenylmethanes. Contact cathartics are most commonly involved in prolonged cathartic abuse. Should never be used > 1 wk of regular therapy. Not recommended for initial therapy.

Name: Castor Oil Class: Laxative (Contact Cathartic)

Name: Lactulose (Constilac, Cephulac) Class: Laxative (Osmotic Laxative)

Name: Lubricant Oils (mineral oil, olive oil, etc.) Class: Laxative Mech.: Coat stomach contents, change consistency of stool, reduce water absorption. Absorption: Oral, enema. Dist.: Metab.: Excretion, t_:

Mech.: Galactose-fructose disaccharide → osmotic effect in small intest. In colon, metab. by bacteria to lactic, formic, and acetic acids → osmotic effect. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Not for use in pts on low galactose diets. Antacids can block fecal acidification (→ ↓ effect on portal-systemic encephalopathy). Neomycin interferes w/lactulose action. Utility: 1° use = symptomatic treatment of portal-systemic encephalopathy assoc. w/chronic liver disease. Acidified feces → ↑ NH4+ excretion. Routine purgation. Special Features: May be preferred for elderly patients for routine purgation, but expensive.

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Mech.: Broken down in small intest. to ricinoleic acid (anionic surfactant) → gut irritation → ↑ peristalsis. ↓ small intest. absorption of electrolytes and water, ↑ speed of transit through GI tract. Effective in as little as 2 hr. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Must not be used chronically → ↓ nutrient absorption. Violent uterine and abdominal cramping. Utility: Laxative Special Features: Contact cathartics are most commonly involved in prolonged cathartic abuse. Should never be used > 1 wk of regular therapy. Not recommended for initial therapy.

Toxicity/S.E.s: Oil absorption → foreign body rxn. Possible lipid pneumonia. Decreased absorption of fat-soluble nutrients. Utility: Laxative. Mineral oil enemas relieve fecal impaction. Special Features: Seldom given orally, as better agents are available.

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Name: Docusates (Colace, Doxinate) Class: Laxative Mech.: Anionic surfactant. Becomes emulsified w/stool → softer feces, easier passage. Requires 1-3 days for action. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: May increase intestinal absorption of other drugs. Don’t use w/lubricant oils. May be mutagenic to cultured liver cells. Utility: Laxative. Use limited to keeping stool soft. Special Features: Only a minimal laxative effect at recommended dosage.

Objections, digressions, gay mistrust, the delight in mockery are signs of health: everything unconditional belongs in pathology. —Nietzsche

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Name: Kaolin-Pectin (Kaopectate) Class: Antidiarrheal Drug (Hydrophilic Agent/Absorbent) Mech.: Kaolin + pectin. Absorb water, bacteria, virus, toxins, bile acids. Decrease fluidity of formed stool. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: May increase water and electrolyte loss. May absorb nutrients, folate, drugs. Utility: Treat diarrhea. Special Features: Not terribly effective.

Name: Diphenoxylate-Atropine (Lomotil) Class: Opioid (Antidiarrheal) Mech.: Increased gastric tone → delayed gastric emptying. ↑ tone and ↓ propulsive peristaltic waves in large intest. → ↓ gut motility. Effects due to inhib. of ACh release by neurons in the intest. wall. Naloxone sensitive. Absorption: Oral Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Recommended dose → dizziness, drowsiness, mild euphoria. Excessive doses → pronounced euphoria, potentially serious respiratory depression (may not be evident until 12-30 hr later). ↓ peristalsis → ↓ evacuation of bacteria and toxins. Use w/great caution in kids. Potentiates effects of barbiturate, tranquilizers, alcohol, other narcotics. Hypertensive crisis w/MAOI. Utility: Antidiarrheal. Special Features: Atropine included primarily to prevent drug abuse. Kids esp. sensitive to atropine toxicity.

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Name: Loperamide (Imodium) Class: Opioid (Antidiarrheal) (OTC) Mech.: Increased gastric tone → delayed gastric emptying. Increase tone and decreased propulsive peristaltic waves in large intest. → decreased gut motility. Effects due to inhib. of ACh release by neurons in the intest. wall. Naloxone sensitive. Anti-secretory effect (non-naloxone sensitive). Absorption: Oral Dist.: 90% → GI tract and liver. Very little CNS. Metab.: Excretion, t_: Toxicity/S.E.s: ↓ peristalsis → ↓ evacuation of bacteria and toxins. Utility: Antidiarrheal. Traveler’s Diarrhea. Special Features: No abuse liability. Preferred anti-diarrheal of the opioids. Less potential for analgesia, respiratory depression, and addiction than other opioids. Much safer than other opioids. Longer lasting effects than diphenoxylate.

Name: Difenoxin-Atropine (Motofen) Class: Opioid (Antidiarrheal) Mech.: Increased gastric tone → delayed gastric emptying. ↑ tone and ↓ propulsive peristaltic waves in large intest. → ↓ gut motility. Effects due to inhib. of ACh release by neurons in the intest. wall. Naloxone sensitive. Absorption: Oral Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Recommended dose → dizziness, drowsiness, mild euphoria. Excessive doses → pronounced euphoria, potentially serious respiratory depression (may not be evident until 12-30 hr later). ↓ peristalsis → ↓ evacuation of bacteria and toxins. Use w/great caution in kids. Potentiates effects of barbiturate, tranquilizers, alcohol, other narcotics. Hypertensive crisis w/MAOI. Utility: Antidiarrheal. Special Features: Difenoxin has 5x potency of diphenoxylate. Atropine included primarily to prevent drug abuse. Kids esp. sensitive to atropine toxicity.

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Name: Paregoric Class: Opioid (Antidiarrheal) Mech.: Preparation of oral morphine, anise oil, benzoic acid, camphor, diluted alcohol, and glycerin. Increased gastric tone → delayed gastric emptying. ↑ tone and ↓ propulsive peristaltic waves in large intest. → ↓ gut motility. Effects due to inhib. of ACh release by neurons in the intest. wall. Naloxone sensitive. Absorption: Oral Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Utility: Antidiarrheal. Special Features:

Name: Norfloxacin (Noroxin) Class: Fluorinated quinolone Mech.: Inhib bact. DNA gyrase (topoisomerase II). Bactericidal. Absorption: Oral admin. Distrib.: Good tissue penetration. Metab.: Excretion, t_: Toxicity/S.E.s: Usu. not severe. GI, CNS. Not for pregnant or nursing women or prepubertal children. Utility: UTIs due to Enterobacteriaceae, Enteroccus, Staph, Pseudomonas. Infectious diarrhea. Special Features: Broader spectrum than nonfluorinated quinolones. For diarrhea, treat until symptoms resolve, or no longer than 3 days.

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Name: Ciprofloxacin (Cipro) Class: Fluorinated quinolone Mech.: Inhib bact. DNA gyrase (topoisomerase II). Bactericidal. Absorption: Rapid absorption after oral admin. Distrib.: Good tissue penetration. Poor CSF. Metab.: Partial hepatic metab. Excretion, t_: Glomerular filtration, secretion. Also feces, bile, sputum. 4 hr. Toxicity/S.E.s: Usu. not severe. GI, CNS, arthropathy. Not for pregnant or nursing women or prepubertal children. Utility: Upper and lower UTIs, DOC for Pseudomonas UTIs. Active against aerobic gram- bacilli, H. influenzae, Neisseria. Good for several causes of infectious diarrhea, osteomyelitis, and patients w/CF. Special Features: Broader spectrum than nonfluorinated quinolones. For diarrhea, treat until symptoms resolve, or no longer than 3 days.

Name: Trimethoprim-Sulfamethoxazole (Bactrim, Septra) Class: Antimicrobial Mech.: Acts on two sequential steps in synth of folic acid. PABA competitive inhib, dihydrofolate reductase inhib. Bacteriostatic. Absorption: Oral, IV Distrib.: Metab.: Excretion, t_: Toxicity/S.E.s: Megaloblastic anemia, leukopenia, granulocytopenia (prevented by admin. of folic acid) Utility: Uncomp. UTIs, otitis media, acute exacerbations of chronic bronchitis, various pneumonias. DOC for Travelers’ diarrhea (esp. in kids), P. carinii pneumonia, Shigella enteritis, systemic Salmonella infects, prostatitis. Special Features: Trimethoprim = highly selective inhib. of bacterial dihydrofolate reductase. For diarrhea, treat until symptoms resolve, or no longer than 3 days.

Name: Ofloxacin (Floxin) Class: Fluorinated quinolone Mech.: Inhib bact. DNA gyrase (topoisomerase II). Bactericidal. Absorption: Oral admin. Distrib.: Good tissue penetration. Metab.: Excretion, t_: Toxicity/S.E.s: Usu. not severe. GI, CNS. Not for pregnant or nursing women or prepubertal children. Utility: UTIs due to Enterobacteriaceae, Enteroccus, Staph, Pseudomonas. Infectious diarrhea. Special Features: Broader spectrum than nonfluorinated quinolones. For diarrhea, treat until symptoms resolve, or no longer than 3 days.

Name: Vitamin D Class: Mech.: Facilitates intest. absorption of Ca2+ and PO43-, and mineralization of bone. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Megadose—hypercalcemia. Utility: Special Features: Quasi-vitamin—synthesized in humans. RDA inversely proportional to amount of UV light exposure. Deficiency → rickets (kids), osteomalacia (adults).

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Name: Vitamin C Class: Mech.: Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Diarrhea. Megadose—diarrhea, kidney stones, precipitation of sickle cell crisis, transient infertility, altered renal secretion of weak acids and bases. Utility: Large doses may reduce rate of buildup of atherosclerotic plaques in coronary arteries and protect against stroke and heart disease. Special Features: TB pts. probably need 2x normal amount of vitamin C.

Name: Vitamin A Class: Mech.: Component of visual pigment. Maintains specialized epithelia and resistance to infxn. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Megadose—teratogenic (face, head, brain, heart), thickening of the leg bones, ↑ intracranial pressure.

Name: Vitamin E Class: Mech.: Fat soluble antioxidant. Scavenges free radicals. Conc. in adipose tissue. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Diarrhea, headache. Utility: Large doses may reduce rate of buildup of atherosclerotic plaques in coronary arteries and protect against stroke and heart disease. Special Features: RDA directly proportional to intake of polyunsaturated fatty acids. Deficiency → spinocerebellar degeneration.

Name: Folic Acid Class: Mech.: Essential for transfer and utilization of 1-carbon units in DNA synth. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s:

Utility: Special Features: Deficiency → night blindness, xerophthalmia, blindness, squamous metaplasia, infxn vulnerability (esp. measles). Liver damage → ↑ need.

Utility: Recommended for all premenopausal women at dose of 2 x RDA → reduced risk of neural tube defects. Lowers homocysteine, reduces risk of heart disease. May lower risk of cervical cancer. Treat folateresponsive schizophrenia (50-150 x RDA → ↓ buildup of urinary homocysteine → ↓ psychiatric symptoms). Special Features: Deficiency → megaloblastic anemia. Alcoholism → ↓ folate absorption. Pregnancy → ↑ folate demand.

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Name: Vitamin K Class: Mech.: Cofactor in hepatic carboxylation of procoagulants—factors II, VII, IX, and X. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Utility: Antagonize coumarin anticoagulation (min. dose = 60-100 x RDA). Infants given injxn (infant GI tract lacks microbes that produce vitamin K).

Name: Vitamin B2 (Riboflavin) Class: Mech.: Converted to coenzymes FMN and FAD. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Utility: Special Features: Deficiency → ariboflavinosis, cheilosis, stomatitis, glossitis, dermatitis, corneal vascularization.

Special Features: Deficiency → bleeding diathesis. Some antibiotics kill gut microbes that synthesize vitamin K. Bishydroxycoumarin antagonizes effects of vitamin K. Prolonged use of large dose salicylates block vitamin K actions in prothrombin synth. → hypoprothrombinemia.

Name: Vitamin B1 (Thiamine) Class: Mech.: Coenzyme in decarboxylation rxns. Facilitates conduction of impulses in peripheral nerves. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Utility: Special Features: Deficiency → dry & wet beriberi, Wernicke-Korsakoff’s synd. RDA directly proportional to caloric intake. Deficiency common in alcoholics.

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Name: Vitamin B6 (Pyridoxine) Class: Mech.: Derivatives serve as coenzymes in many intermed. rxns. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Megadose—severe (often irreversible) sensory neuropathy Utility: Special Features: Deficiency → cheilosis, glossitis, dermatitis, peripheral neuropathy. Liver damage → ↑ need. Penicillamine, hydralazine, and isoniazid complex w/B6 → ↓ B6. B6 is a cofactor of tryptophan → nicotinic acid conversion. Results in ↓ B3. Pregnancy → ↑ B6 demand.

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Name: Vitamin B3 (Niacin) Class: Mech.: Incorporated into NAD and NADP. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Utility: Special Features: Deficiency → pellagra (dementia, dermatitis, diarrhea). Penicillamine, hydralazine, and isoniazid complex w/B6 → ↓ B6. B6 is a cofactor of tryptophan → nicotinic acid conversion. Results in ↓ B3.

Name: Vitamin B12 (Cyanocobalamin) Class: Mech.: Necessary for folate metabolism and DNA synth. Maintains myelinization of spinal cord tracts. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Utility: Special Features: Vegan diet → deficiency → megaloblastic pernicious anemia and degeneration of posterolateral spinal cord tracts. If patient is deficient in B12 and folate, replace B12 first to avoid irreversible neuro damage. Liver damage → ↑ need.

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Name: Biotin Class: Mech.: Incorporated in coenzyme A. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Utility: Special Features: Some antibiotics kill gut microbes that synthesize biotin.

Name: Iodine Class: Mech.: 80% contained in thyroglobulin. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Utility: Special Features: Deficiency → endemic goiter. Excess (>20 x RDA) → blocked organification of iodine → myxedema.

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Name: Zinc Class: Mech.: Part of many metalloproteins (e.g., “zinc fingers”). Element of carbonic anhydrase. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Utility: Special Features: Kids w/low Zinc often grow poorly and have a poor appetite (prob. 2° to impaired taste).

Name: Copper Class: Mech.: Present in muscle, bone, liver, blood. In blood, almost entirely bound to ceruloplasmin. Component of many metalloenzymes such as cytochrome oxidase and tyrosinase. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Utility: Special Features: Excess plasma free copper may be due to Wilson’s Disease (defective ceruloplasmin) or excessive intake.

Name: Selenium Class: Mech.: Present in glutathione peroxidase which destroys peroxides derived from unsaturated fatty acids. Probably has a close functional relationship w/vitamin E. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Utility: Special Features: RDA probably directly proportional to intake of polyunsaturated fatty acids.

Name: Fluoride Class:

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Mech.: Present in bones and teeth. Fluoridation of drinking water at 1 ppm → ↓ dental caries by 30-40%. Hardens outer layers of tooth enamel. Makes enamel more resistant to demineralization. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Utility: Special Features: Excess (> 10 ppm in water) → fluorosis (mottling of teeth) due to excess accumulation in teeth and bones.

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Name: Manganese Class: Mech.: Present in several enzymes, required for normal bone structure. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Utility: Special Features: No reported deficiencies. Excess limited to manganese miners.

Name: Chromium Class: Mech.: Part of several metalloenzymes Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Utility: Special Features: Deficiencies only in severely protein-deprived pts and pts. w/prolonged parenteral feeding.

Name: Cobalt Class: Mech.: Present in vitamin B12. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Utility: Special Features: No known deficiency states.

For one thing is needful: that a human being attain satisfaction with himself - whether it be by this or by that poetry and art; only then is a human being at all tolerable to behold. Whoever is dissatisfied with himself is always ready to revenge himself; and therefore we will be his victims if only by always having to stand his ugly sight. For the sight of the ugly makes men bad and gloomy. - Nietzsche

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Name: Mechlorethamine (Mustargan) Class: Antineoplastic (Cell Cycle-Nonspecific) (Alkylating Agent) (Mustard)

Name: Chlorambucil (Leukeran) Class: Antineoplastic (Cell Cycle-Nonspecific) (Alkylating Agent) (Mustard)

Mech.: Alkylates DNA → crosslinkages.

Mech.: Alkylates DNA → crosslinkages.

Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: N/V. DLT = bone marrow suppression, esp. leukocytosis. Max. suppression at 10-12 days, recovery around 42 days. Utility: Hodgkin’s disease (in combination therapy—MOPP). Special Features: Fast-acting. Active against a wide variety of cancers. Not widely used due to toxicity.

Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Seizures DLT = bone marrow suppression, pulmonary fibrosis. Utility: CLL Special Features: Slow-acting. Good activity against some chronic cancers.

Name: Melphalan (Alkeran) Class: Antineoplastic (Cell Cycle-Nonspecific) (Alkylating Agent) (Mustard)

Name: Cyclophosphamide (Cytoxan) Class: Antineoplastic (Cell Cycle-Nonspecific) (Alkylating Agent) (Mustard)

Mech.: Alkylates DNA → crosslinkages.

Mech.: Alkylates DNA → crosslinkages.

Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Nausea, hypersensitivity rxns. DLT = bone marrow suppression, esp. platelets. Utility: Multiple myeloma. Special Features: Slow-acting. Good activity against some chronic cancers.

Absorption: Oral (preferred), IV. Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: N/V. Anaphylaxis rxns. DLT = bone marrow suppression. Max. suppression at 10-12 days, recovery by 21 days. Hemorrhagic cystitis, sterility. Utility: Non-Hodgkin’s lymphomas, cancers of breast and ovary, Wilm’s tumor, rhabdosarcoma, Burkitt’s lymphoma. Special Features: Most useful alkylating agent. Requires metabolic activation. Fast-acting. Active against a wide variety of cancers.

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Name: BCNU (Carmustine) Class: Antineoplastic (Cell Cycle-Nonspecific) (Alkylating Agent) (Nitrosourea)

Name: CCNU (Lomustine) Class: Antineoplastic (Cell Cycle-Nonspecific) (Alkylating Agent) (Nitrosourea)

Mech.: Alkylates DNA → crosslinkages.

Mech.: Alkylates DNA → crosslinkages.

Absorption: Dist.: Crosses BBB. Metab.: Excretion, t_: Toxicity/S.E.s: N/V. DLT = bone marrow suppression. Max. suppression at 28 days, recovery around 42 days. Pulmonary fibrosis, renal toxicity. Utility: Hodgkin’s and non-Hodgkin’s lymphomas, primary glioblastoma, brain tumors. Special Features: Fast-acting. Active against a wide variety of cancers. Not widely used due to toxicity.

Absorption: Crosses BBB. Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: N/V. DLT = bone marrow suppression. Max. suppression at 28 days, recovery around 42 days. Pulmonary fibrosis, renal toxicity. Utility: Hodgkin’s and non-Hodgkin’s lymphomas, primary glioblastoma, brain tumors. Special Features: Fast-acting. Active against a wide variety of cancers. Not widely used due to toxicity.

Name: Streptozocin (Zanosar) Class: Antineoplastic (Cell Cycle-Nonspecific) (Alkylating Agent) (Nitrosourea) Mech.: Alkylates DNA Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: N/V. DLT = renal damage in 2/3 patients. Hypo/hyperglycemia, liver toxicity. Utility: Malignant pancreatic insulinoma, pancreatic carcinoid. Special Features:

Name: Busulfan (Myleran) Class: Antineoplastic (Cell Cycle-Nonspecific) (Alkylating Agent) Mech.: Alkylates DNA. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: N/V. DLT = leukopenia and thrombocytopenia. Utility: CML (chronic phase). Special Features:

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Name: Procarbazine (Mutalane) Class: Antineoplastic (Cell Cycle-Nonspecific) (Alkylating Agent) Mech.: Alkylates DNA. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: N/V. Leukopenia and thrombocytopenia. Inhib. MAO (danger w/tyramine-containing foods). Disulfiram-type rxn w/alcohol. Utility: Hodgkin’s disease. Special Features:

Name: Dacarbazine (DTIC) Class: Antineoplastic (Cell Cycle-Nonspecific) (Alkylating Agent) Mech.: Alkylates DNA. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: N/V. Leukopenia and thrombocytopenia. Utility: Melanoma. Special Features:

Name: Cisplatin (Platinol) Class: Antineoplastic (Cell Cycle-Nonspecific)

Name: Carboplatin (Paraplatin) Class: Antineoplastic (Cell Cycle-Nonspecific)

Mech.: Forms coordinate covalent bonds in DNA → inter- and intrastrand crosslinks → inhib. of DNA and RNA synth.

Mech.: Forms coordinate covalent bonds in DNA → inter- and intrastrand crosslinks → inhib. of DNA and RNA synth.

Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Major N/V, hearing loss at high end. DLT = kidney toxicity. Utility: Curative for testicular tumors. Small cell lung, head, neck tumors. Special Features: Prophylaxis w/5HT3 antagonists (e.g., Ondansetron) may help with N/V. Renal toxicity can be minimized by adequate hydration and production of elevated urine volumes.

Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Mild N/V. DLT = myelosuppression. Utility: Curative for testicular tumors. Small cell lung, head, neck tumors. Special Features:

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Name: Doxorubicin (Adriamycin) Class: Antineoplastic (Cell Cycle-Nonspecific) (Antibiotic) (Anthracycline)

Name: Mitoxantrone (Novantrone) Class: Antineoplastic (Cell Cycle-Nonspecific) (Antibiotic) (Anthracycline)

Mech.: Intercalation into DNA → stabilization of topoisomerase II-DNA cleavable complexes → DNA breaks. Quinone structure reduced by cyt. P-450 → oxygen radical production → DNA strand breaks. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Myelosuppression—max. in week 2, recovery in week 4. Radiation recall (hypersensitivity and necrosis in prev. or subseq. irradiated tissue). DLT = cardiomyopathy in 1/3 of pts if total dose exceeds 550 mg/m2. Utility: One of the most useful cancer drugs. Soft-tissue tumors, osteogenic and other sarcomas, small cell CA of lung, Hodgkin’s and non-Hodgkin’s lymphomas, acute leukemias, others. Special Features:

Mech.: Intercalation into DNA → interference w/topoisomerase II-catalyzed breakage-reunion reaction of DNA strands to cause unreparable breaks. Quinone structure reduced by cyt. P-450 → oxygen radical production → DNA strand breaks. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Myelosuppression—max. in week 2, recovery in week 4. Radiation recall. DLT = cardiomyopathy. Utility: One of the most useful cancer drugs. Soft-tissue, osteogenic and other sarcomas, small cell CA of lung, Hodgkin’s and non-Hodgkin’s lymphomas, acute leukemias, others. Special Features: Synthetic doxorubicin with reduced cardiotoxicity.

Name: Daunomycin (Daunorubicin) Class: Antineoplastic (Cell Cycle-Nonspecific) (Antibiotic) (Anthracycline)

Name: Dactinomycin (Actinomycin D, Cosmegen) Class: Antineoplastic (Cell Cycle-Nonspecific) (Antibiotic)

Mech.: Intercalation into DNA → stabilization of topoisomerase II-DNA cleavable complexes → DNA breaks. Quinone structure reduced by cyt. P-450 → oxygen radical production → DNA strand breaks. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Myelosuppression—max. in week 2, recovery in week 4. Radiation recall. DLT = cardiomyopathy in 1/3 of pts if total dose exceeds 550 mg/m2 Utility AML (+ cytarabine). Special Features:

Mech.: Intercalation into DNA (small groove between G-C pairs) → stable dactinomycin-DNA complex → interference w/DNA-dependent RNA polymerase. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: N/V. Radiation recall. DLT = bone marrow suppression. Immunosuppression. Utility Choriocarcinoma, Wilm’s tumor, others. Special Features:

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Name: Mitomycin C (Mutamycin) Class: Antineoplastic (Cell Cycle-Nonspecific) (Antibiotic) (Quinone) Mech.: DNA alkylation/adduction, formation of oxygen radicals. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: N/V. DLT = bone marrow suppression (cumulative). Very toxic. Utility: Bladder cancer, some GI cancers. Special Features:

Name: Bleomycin (Blenoxane) Class: Antineoplastic (Cell Cycle-Specific) (Antibiotic) Mech.: Binds DNA and copper or iron. The metals generate reactive oxygen species → double strand breaks in DNA.

Name: 5-FU/5-Fluorouracil (Adrucil) Class: Antineoplastic (Cell Cycle-Specific) (Antimetabolite) (Pyrimidine Analog)

Name: Cytarabine/ara-C (Cytosar-U) Class: Antineoplastic (Cell Cycle-Specific) (Antimetabolite) (Pyrimidine Analog) Mech.: Inhibits DNA synthesis. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: GI toxicity, N/V. DLT = bone marrow suppression. Utility: AML. + daunomycin for CML, acute phase. Special Features:

Mech.: Inhibits thymidine synthesis → ↓ DNA synthesis. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: N/V, GI toxicity. DLT = bone marrow suppression. Utility: Solid, slow growing tumors, including breast, colon, ovarian, pancreatic, and gastric carcinomas. Used topically for premalignant skin lesions, basal cell carcinomas. Special Features:

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Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: N/V, skin toxicity. DLT = pulmonary fibrosis at total dose of 400 units (can be fatal). Utility: Testicular tumors (curative), head and neck tumors, cervical tumors, squamous cell CA, lymphomas. Special Features: Myelosuppression is rare.

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Name: 6-Mercocaptopurine/6-MP (Purinethol) Class: Antineoplastic (Cell Cycle-Specific) (Antimetabolite) (Guanine Analog) Mech.: Inhibits DNA and protein synthesis. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: N/V. DLT = bone marrow suppression. Utility: Maintenance of remission of ALL. Special Features:

Name: Methotrexate (Amethopterine) Class: Antineoplastic (Cell Cycle-Specific) (Antimetabolite) (Folic Acid Analog) Mech.: Inhib. dihydrofolate reductase and thymidylate synthase → ↓ DNA synth. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: GI toxicity, N/V. DLT = bone marrow suppression. Renal tubular damage w/↑ doses Utility: Curative for choriocarcinoma and osteogenic sarcoma. ALL maintenance. Breast cancer. Special Features: Follow treatment w/leucovorin admin. to rescue the bone marrow.

Name: Leucovorin Class: Adjunct to Methotrexate Anti-Cancer Chemotherapy Mech.: Folinic acid. Converted to N5N10-methylene FH4 (reduced folate). Bypasses inhibited dihydrofolate reductase (courtesy of methotrexate) → renewed DNA synth. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Utility: Used after methotrexate treatment to rescue patient’s bone marrow. Special Features:

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Name: Etoposide (VP-16, Vepesid) Class: Antineoplastic (Cell Cycle-Specific) (Podophylin) Mech.: Binds topoisomerase II-DNA complex → persistence of transient cleavable form → ↑ susceptibility to irreversible double strand breaks. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: N/V. DLT = bone marrow suppression. Utility: Testicular CA, oat cell CA of the lung. Special Features:

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Name: Vincristine (Oncovin) Class: Antineoplastic (Cell Cycle-Specific) (Vinca Alkaloid)

Name: Vinblastine (Velban) Class: Antineoplastic (Cell Cycle-Specific) (Vinca Alkaloid)

Mech.: Binds tubulin → prevention of microtubule formation → block of mitosis in metaphase. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: N/V. Bone marrow suppression. DLT = neurotoxicity. Utility: Hodgkin’s disease and other lymphomas. ALL in kids, Wilm’s tumor, Ewing’s soft-tissue sarcomas. Special Features:

Mech.: Binds tubulin → prevention of microtubule formation → block of mitosis in metaphase. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: N/V. DLT = Bone marrow suppression. Utility: Hodgkin’s disease and other lymphomas, testicular tumors + bleomycin and cisplatin. Special Features:

Name: Taxol (Paclitaxel) Class: Antineoplastic (Cell Cycle-Specific)

Name: Prednisone Class: Antineoplastic (Hormone) (Corticosteroid) Mech.: Suppresses mitosis in lymphocytes. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Cushingoid symptoms. Utility: Acute leukemias in kids, CLL, palliative effects in some adult cancers. Special Features:

Mech.: Binds tubulin → polymerization and stabilization of microtubules → dysfunctional tubules (i.e., cell locked in metaphase) → cell death. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: DLT = Neutropenia. Severe hypersensitivity rxns. Utility: Ovarian and breast cancers. Special Features: Vomiting and diarrhea are uncommon.

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Name: Tamoxifen (Nolvadex) Class: Antineoplastic (Hormone) (Estrogen Analog)

Name: Leuprolide (Lupron) Class: Antineoplastic (Hormone) (GnRH Analog)

Mech.: Antiestrogen → depletion of estrogen receptors. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Rarely severe. N/V, hot flashes. Utility: Estrogen receptor positive breast cancer. Has potential to cause endometrial cancer. Special Features:

Mech.: Occupies GnRH receptor in pituitary → desensitization → inhib. of release of FSH and LH. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Less toxic than DES. N/V, hot flashes, impotence. Utility: Prostatic cancer. Special Features:

Name: Goserelin (Zoladex) Class: Antineoplastic (Hormone) (GnRH Analog)

Name: Flutamide (Eulixen) Class: Antineoplastic (Hormone) (Testosterone Receptor Antagonist)

Mech.: Occupies GnRH receptor in pituitary → desensitization → inhib. of release of FSH and LH. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Less toxic than DES. N/V, hot flashes, impotence. Utility: Prostatic cancer. Special Features:

Mech.: Binds androgen receptors → block of inhibitory effect of testosterone on gonadotropin secretion → ↑ serum LH and testosterone. Blocks actions of testosterone on prostate gland. Absorption: Oral. Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Gynecomastia, GI distress. Utility: Prostatic cancer. Special Features: Always administered with leuprolide or goserelin.

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Name: Interferon α Class: Immunostimulant

Name: Bacillus Calumet-Guerin (BCG) Class: Immunostimulant

Mech.: Binds to cell-surface receptors → inhib. of viral replication, inhib. of cell proliferation. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Fever w/chills; dose-related leukopenia, thrombocytopenia; fatigue, malaise, anorexia, weight loss, alopecia, transient elevation of liver enzymes. High doses may → transient & reversible nephrotoxicity.

Mech.: Viable strain of Mycobaterium bovis. Enhances Mφ activity, promotes Mφ tumoricidal activity. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Utility: Treat bladder carcinoma and melanomas. Special Features:

Utility: IFN α2A is approved for mgt. of hairy cell leukemia. Also useful for chronic hepatitis B, virally induced tumors, recurrent varicella zoster, HSV keratitis, Kaposi’s sarcoma, cutaneous T cell lymphoma. Special Features: Produced by mononuclear leukocytes. Interferon production is induced by dsRNA (poly I:C), ampligen (mismatched nucleotides), LPS.

Name: Levamisole (Ergamisol) Class: Slow-Acting Antirheumatic Agent (Veterinary Anti-Helminthic Agent) Mech.: Enhances cell-mediated immune responses (↑ chemotaxis & phagocytosis of PMNs and Mφs, ↑ T cell fxn). How these effects ameliorate RA is unknown. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Rash (most common), leukopenia, agranulocytosis, thrombocytopenia, influenza-like illnesses, mouth ulcers, n/v. Utility: Treat rheumatoid arthritis (off-label use). + 5-Fluorouracil for colonic cancer. Special Features:

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There is an ancient story that King Midas hunted in the forest a long time for the wise Silenus, the companion of Dionysus, without capturing him. When Silenus at last fell into his hands, the king asked what was the best and most desirable of all things for man. Fixed and immovable, the demigod said not a word, till at last, urged by the king, he gave a shrill laugh and broke out into these words: “Oh, wretched ephemeral race, children of chance and misery, why do you compel me to tell you what it would be most expedient for you not to hear? What is best of all is utterly beyond your reach: not to be born, not to be, to be nothing. But the second best for you is - to die soon.” - Nietzsche

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Name: Acetylsalicylic Acid/Aspirin Class: Salicylate Mech.: Irrevers. acetylation of cyclooxygenase → inhib. of prostaglandin synth. → ↓ prostaglandins, thromboxanes, & prostacyclins → analgesia, inhib. of platelet aggregation, anti-inflammatory effects, anti-pyresis, stim. of central resp. center. Absorption: Rapidly absorbed in stomach and upper intestine. Also absorbed through skin. pKa = 3.5, so gastric acid → ↑ absorption. Enteric coating may delay absorption. Dist.: pH-dependent passive (non-ionic) diffusion. Active transport in renal tubules. 90% bound to albumin. Metab.: Hydrolyzed by tissue/blood esterases. Conjugated in liver. Excretion, t_: Salicylate & metabolites excreted in urine. pH-dependent—30% excretion in alkaline urine, 2% in acidic urine. Low doses (600 mg) = 1st order; t_ = 3-5 hr. High doses (4 g/d) = 0 order, t_ = 15 hr. Utility: Analgesia—mild-mod. pain, somatic pain. No dependence or tolerance. Low efficacy for visceral pain. Anti-inflammatory—also a mech. of analgesia. Anti-pyresis—inhib. bacterial pyrogens in CNS; blocks hypothalamic response to IL-1. ↓ Platelet aggregation—2° to inhib. of thromboxane synth.

Aspirin cont. Toxicity/S.E.s: GI bleeding and ulceration—usu. due to high doses, but may occur w/lower doses. Painless bleeding may cause iron-deficiency anemia. Hypersensitivity—usu. in patients w/nasal polyps, asthma, or chronic urticaria → urticaria, angioedema, hypotension. Bleeding—C/i w/severe hepatic damage, vit. K deficiency, hemophilia. Hepatotoxicity w/CT disorders. May be involved in Reye’s Synd.; not recommended for kids w/chicken pox or influenza. Pregnancy—reduced birth weight, ↑ perinatal mortality, ante/post-partum hemorrhage, prolonged gestation. Renal effects—low doses → ↓ uric acid excretion; high doses → ↑ uric acid excretion. Poisoning—acute → resp. alkalosis (hyperventilation), metabolic acidosis (fixed anion). Correlates w/plasma conc. Chronic → higher brain conc. than in acute poisoning; greater toxicity than plasma conc. would suggest. More resistant to treatment than acute poisoning. Drug Interactions: Alcohol → ↑ gastric bleeding. Displacement of oral hypoglycemia drugs, NSAIDS, methotrexate, phenytoin, oral anti-coagulants, & sulfonamides from protein binding sites. Special Features: May exacerbate acute gout attacks.

Name: Methylsalicylate (Oil of Wintergreen) Class: Salicylate Mech.: Absorption: Absorbed transdermally. Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Used in foods…may be toxic. Utility: Used in liniments for cutaneous counterirritation. Special Features:

Name: Salicylamide Class: Salicylate Mech.: Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Utility: Special Features: May exacerbate acute gout attacks. ???

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Name: Ibuprofen (Advil, Motrin, Nuprin) (OTC) Class: NSAID Mech.: Inhibition of cyclooxygenase → inhibition of prostaglandin synthesis. Also inhib. of PMN adhesion, aggregation, & activation (ramifications uncertain). Absorption: Oral. Absorbed from stomach and upper intestine. Peak conc. 1-2 hr. Dist.: Weak acid (pKa <5). ~90% protein binding. Vd ≅ albumin Vd. Metab.: 1° = liver. Phase I (oxid.) & Phase II (conjug.). Excretion, t_: Metabolites in urine. Renal failure → retention of glucuronide metabolites → potential for toxic accumulation of orig. compound. t_ = 2-3 hr. Toxicity/S.E.s: GI—esophagitis & esophageal strictures; gastroduodenal erosions, ulceration, hemorrhage, & perforation; ileal inflammation, strictures, hemorrhage, & perforation; colon hemorrhage and exacerbation of inflammatory bowel disease. Hypersensitivity—possible cross-reaction w/aspirin. Inhib. of platelet aggregation. Kidney—Na+ retention, hemodynamic renal failure, interstitial nephritis. CNS—dizziness, tinnitus, headache, aseptic meningitis. Overdose—Acute is less serious than w/aspirin, but may cause metabolic acidosis & seizures. Utility: Treat pain, inflammation, dysmenorrhea, patent ductus arteriosis, acute gout.

Name: Indomethacin (Indocin) Class: NSAID Mech.: Inhibition of cyclooxygenase → inhibition of prostaglandin synthesis. Also inhib. of PMN adhesion, aggregation, & activation (ramifications uncertain). Absorption: Oral. Absorbed from stomach and upper intestine. Peak conc. 1-2 hr. Dist.: Weak acid (pKa <5). ~90% protein binding. Vd ≅ albumin Vd. Metab.: 1° = liver. Phase I (oxid.) & Phase II (conjug.). Excretion, t_: Metabolites in urine, bile, & feces. Renal failure → retention of glucuronide metabolites→potential for toxic accum. of orig. compound. t_=4-5 hr. Decreased clearance w/hepatic/renal impairment & in the elderly. Toxicity/S.E.s: GI—esophagitis & esophageal strictures; gastroduodenal erosions, ulceration, hemorrhage, & perforation; ileal inflammation, strictures, hemorrhage, & perforation; colon hemorrhage and exacerbation of inflammatory bowel disease. Hypersensitivity—possible crossreaction w/aspirin. Inhib. of platelet aggregation. Kidney—Na+ retention, hemodynamic renal failure, interstitial nephritis. CNS—dizziness, tinnitus, headache, aseptic meningitis. Overdose—Acute is less serious than w/aspirin, but may cause metabolic acidosis & seizures. Use limited by toxicity. 100% cross-reactivity with aspirin. Utility: Treat pain, inflammation, dysmenorrhea, patent ductus arteriosis, acute gout. Special Features: Most commonly used NSAID for acute gout attack due to short peak time & rapid clearance.

Name: Sulindac (Clinoril) Class: NSAID Mech.: Inhibition of cyclooxygenase → inhibition of prostaglandin synthesis. Also inhib. of PMN adhesion, aggregation, & activation (ramifications uncertain). Absorption: Oral. Absorbed from stomach and upper intestine. Peak conc. 1-2 hr. Dist.: Weak acid (pKa <5). ~90% protein binding. Vd ≅ albumin Vd. Metab.: 1° = liver. Phase I (oxid.) & Phase II (conjug.). Excretion, t_: Metabolites in urine, bile, feces. Renal failure → retention of glucuronide metabolites → potential for toxic accumulation of orig. compound. t_ = 8-16 hr. Decreased clearance w/hepatic impairment and in the elderly. Toxicity/S.E.s: GI—esophagitis & esophageal strictures; gastroduodenal erosions, ulceration, hemorrhage, & perforation; ileal inflammation, strictures, hemorrhage, & perforation; colon hemorrhage and exacerbation of inflammatory bowel disease. Hypersensitivity—possible cross-reaction w/aspirin. Inhib. of platelet aggregation. Kidney—Na+ retention, hemodynamic renal failure, interstitial nephritis, but less likely to cause kidney effects than other NSAIDs. CNS—dizziness, tinnitus, headache, aseptic meningitis. Overdose—Acute is less serious than w/aspirin, but may cause metabolic acidosis & seizures. Utility: Treat pain, inflammation, dysmenorrhea, patent ductus arteriosis, acute gout. Special Features: Pro drug (converted to an active metabolite).

Name: Flurbiprofen (Ansaid) Class: NSAID Mech.: Inhibition of cyclooxygenase → inhibition of prostaglandin synthesis. Also inhib. of PMN adhesion, aggregation, & activation (ramifications uncertain). Absorption: Oral. Absorbed from stomach and upper intestine. Peak conc. 1-5 hr. Dist.: Weak acid (pKa <5). ~90% protein binding. Vd ≅ albumin Vd. Metab.: 1° = liver. Phase I (oxid.) & Phase II (conjug.). Excretion, t_: Metabolites in urine. Renal failure → retention of glucuronide metabolites → potential for toxic accumulation of orig. compound. t_ = 5 hr. Toxicity/S.E.s: GI—esophagitis & esophageal strictures; gastroduodenal erosions, ulceration, hemorrhage, & perforation; ileal inflammation, strictures, hemorrhage, & perforation; colon hemorrhage and exacerbation of inflammatory bowel disease. Hypersensitivity—possible cross-reaction w/aspirin. Inhib. of platelet aggregation. Kidney—Na+ retention, hemodynamic renal failure, interstitial nephritis. CNS—dizziness, tinnitus, headache, aseptic meningitis. Overdose—Acute is less serious than w/aspirin, but may cause metabolic acidosis & seizures. Utility: Treat pain, inflammation, dysmenorrhea, patent ductus arteriosis, acute gout.

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Name: Naproxen (Naprosyn) Class: NSAID Mech.: Inhibition of cyclooxygenase → inhibition of prostaglandin synthesis. Also inhib. of PMN adhesion, aggregation, & activation (ramifications uncertain). Absorption: Oral. Absorbed from stomach and upper intestine. Peak conc. 2-4 hr. Dist.: Weak acid (pKa <5). ~90% protein binding. Vd ≅ albumin Vd. Metab.: 1° = liver. Phase I (oxid.) & Phase II (conjug.). Excretion, t_: Metabolites in urine. Renal failure → retention of glucuronide metabolites→potential for toxic accumulation of orig. compound. t_ = 12-15 hr. Clearance decreased w/renal/hepatic impairment & in the elderly. Toxicity/S.E.s: GI—esophagitis & esophageal strictures; gastroduodenal erosions, ulceration, hemorrhage, & perforation; ileal inflammation, strictures, hemorrhage, & perforation; colon hemorrhage and exacerbation of inflammatory bowel disease. Hypersensitivity—possible cross-reaction w/aspirin. Inhib. of platelet aggregation. Kidney—Na+ retention, hemodynamic renal failure, interstitial nephritis. CNS—dizziness, tinnitus, headache, aseptic meningitis. Overdose—Acute is less serious than w/aspirin, but may cause metabolic acidosis & seizures. Utility: Treat pain, inflammation, dysmenorrhea, patent ductus arteriosis, acute gout.

Name: Piroxicam (Feldene) Class: NSAID Mech.: Inhibition of cyclooxygenase → inhibition of prostaglandin synthesis. Also inhib. of PMN adhesion, aggregation, & activation (ramifications uncertain). Absorption: Oral. Absorbed from stomach and upper intestine. Peak conc. 3-5 hr. Dist.: Weak acid (pKa <5). ~90% protein binding. Vd ≅ albumin Vd. Metab.: 1° = liver. Phase I (oxid.) & Phase II (conjug.). Excretion, t_: Metabolites in urine. Renal failure → retention of glucuronide metabolites→potential for toxic accumulation of orig. compound. t_ = 30-86 hr. Toxicity/S.E.s: GI—esophagitis & esophageal strictures; gastroduodenal erosions, ulceration, hemorrhage, & perforation; ileal inflammation, strictures, hemorrhage, & perforation; colon hemorrhage and exacerbation of inflammatory bowel disease. Hypersensitivity—possible cross-reaction w/aspirin. Inhib. of platelet aggregation. Kidney—Na+ retention, hemodynamic renal failure, interstitial nephritis. CNS—dizziness, tinnitus, headache, aseptic meningitis. Overdose—Acute is less serious than w/aspirin, but may cause metabolic acidosis & seizures. Utility: Treat pain, inflammation, dysmenorrhea, patent ductus arteriosis, acute gout.

Name: Diflunisal (Dolobid) Class: Salicylate. Mech.: Inhibition of cyclooxygenase → inhibition of prostaglandin synthesis. Also inhib. of PMN adhesion, aggregation, & activation (ramifications uncertain). Absorption: Oral. Absorbed from stomach and upper intestine. Peak conc. 2-3 hr. Dist.: Weak acid (pKa <5). ~90% protein binding. Vd ≅ albumin Vd. No CNS. Metab.: 1° = liver. Phase I (oxid.) & Phase II (conjug.). Excretion, t_: Metabolites in urine. Renal failure → retention of glucuronide metabolites→potential for toxic accumulation of orig. compound. t_ = 11-15 hr. Clearance decreased w/renal impairment & in the elderly. Toxicity/S.E.s: GI—esophagitis & esophageal strictures; gastroduodenal erosions, ulceration, hemorrhage, & perforation; ileal inflammation, strictures, hemorrhage, & perforation; colon hemorrhage and exacerbation of inflammatory bowel disease. Hypersensitivity—possible cross-reaction w/aspirin. Inhib. of platelet aggregation. Kidney—Na+ retention, hemodynamic renal failure, interstitial nephritis. CNS—dizziness, tinnitus, headache, aseptic meningitis. Overdose—Acute is less serious than w/aspirin, but may cause metabolic acidosis & seizures. Utility: Treat pain, inflammation, dysmenorrhea, patent ductus arteriosis, acute gout. Special Features: Not metab. to salicylate, ∴ no salicylate intoxication. No CNS → no antipyretic properties. 3-4x more potent than aspirin.

Name: Ketorolac (Toradol) Class: NSAID Mech.: Inhibition of cyclooxygenase → inhibition of prostaglandin synthesis. Also inhib. of PMN adhesion, aggregation, & activation (ramifications uncertain). Absorption: Parenteral only. Dist.: Weak acid (pKa <5). ~90% protein binding. Vd ≅ albumin Vd. Metab.: 1° = liver. Phase I (oxid.) & Phase II (conjug.). Excretion, t_: Metabolites in urine. Renal failure → retention of glucuronide metabolites → potential for toxic accumulation of orig. compound. Toxicity/S.E.s: GI—esophagitis & esophageal strictures; gastroduodenal erosions, ulceration, hemorrhage, & perforation; ileal inflammation, strictures, hemorrhage, & perforation; colon hemorrhage and exacerbation of inflammatory bowel disease. Hypersensitivity—possible cross-reaction w/aspirin. Inhib. of platelet aggregation. Kidney—Na+ retention, hemodynamic renal failure, interstitial nephritis. CNS—dizziness, tinnitus, headache, aseptic meningitis. Overdose—Acute is less serious than w/aspirin, but may cause metabolic acidosis & seizures. Utility: Treat pain, inflammation, dysmenorrhea, patent ductus arteriosis, acute gout. May be as effective as morphine or meperidine for short-term relief of mod.-severe pain.

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Name: Gold (Auranofin, Aurothioglucose) Class: Slow-Acting Antirheumatic Agent Mech.: Unknown. May involve alteration of macrophage fxn. Absorption: Auranofin—oral. Aurathioglucose—IM. Dist.: 95% protein bound. Metab.: Excretion, t_: 65% in urine, 35% feces. 5-6 days. Toxicity/S.E.s: Affects about 1/3 of patients. Mucocutaneous—pruritis & dermatitis. Renal—proteinuria, nephrotic synd., hematuria. Hematologic—eosinophilia, thrombocytopenia, aplastic anemia. Utility: Treatment of patients w/rheumatoid arthritis who are unresponsive to NSAIDs or whose symptoms persist despite maximal tolerated doses of NSAIDs. Special Features:

Name: D-penicillamine (Cuprimine) Class: Slow-Acting Antirheumatic Agent Mech.: Unknown. Suppresses/modifies immune system & interacts w/leukocyte membrane receptors. Also chelates heavy metals (e.g., Pb, Hg, As, Cu). Absorption: Oral. Dist.: 80% protein bound. Metab.: Excretion, t_: Urine. Toxicity/S.E.s: Mucocutaneous—pruritis, dermatitis. Renal—proteinuria, nephrotic synd. Hematologic—thrombocytopenia, aplastic anemia. Pulmonary—hemorrhagic pneumonitis. Utility: Treatment of patients w/rheumatoid arthritis who are unresponsive to NSAIDs or whose symptoms persist despite maximal tolerated doses of NSAIDs. Special Features:

Name: Methotrexate (Rheumatrex) Class: Slow-Acting Antirheumatic Agent (Antimetabolite) Mech.: Inhib. dihydrofolate reductase → inhib. of formation of tetrahydrofolic acid → ↓ synth of purines, thymidylic acid, methionine, and serine → ↓ DNA/RNA/protein synth. → eventual cell death. Absorption: Oral, IV, IM, IT. Dist.: No CNS unless administered IT. Metab.: Excretion, t_: Toxicity/S.E.s: Stomatitis, myelosuppression, erythema, rash, urticaria, alopecia, n/v/d. Long term use may → hepatic fibrosis. High doses may → crystalluria. Patient must be well hydrated and have alkaline urine to avoid renal toxicity. Also pulmonary toxicity in children. IT admin. → subacute meningeal irritation, stiff neck, headache, fever; rarely seizures, encephalopathy, paraplegia. C/i w/pregnancy (teratogenic). Utility: Low doses useful in treating rheumatoid arthritis and severe psoriasis. Effective against acute lymphocytic leukemia, choriocarcinoma, Burkitt’s lymphoma, breast cancer, head/neck carcinomas. High doses are curative for osteogenic sarcoma and choriocarcinoma.

Name: Hydroxychloroquine (Plaquenil) Class: Slow-Acting Antirheumatic Agent (Anti-Malarial Agent) Mech.: Unknown. Inhib. nucleic acid synth, stabilizes lysosomal membranes, traps free radicals. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: GI upset, pruritis, headaches, visual disturbances, discoloration of nail beds and mucous membranes. Utility: Treat rheumatoid arthritis that has been unresponsive to NSAIDs. Also used to treat rheumatoid arthritis in conjunction w/an NSAID (allows use of lower dose of hydroxychloroquine). Special Features:

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Name: Sulfasalazine (Azulfidine) Class: Sulfonamide (Slow-Acting Antirheumatic Agent)

Name: Levamisole (Ergamisol) Class: Slow-Acting Antirheumatic Agent (Veterinary Anti-Helminthic Agent)

Mech.: Comp. inhib. of PABA incorp. into dihydropteric acid → inhib. of folic acid.

Mech.: Enhances cell-mediated immune responses (↑ chemotaxis & phagocytosis of PMNs and Mφs, ↑ T cell fxn). How these effects ameliorate RA is unknown. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Rash (most common), leukopenia, agranulocytosis, thrombocytopenia, influenza-like illnesses, mouth ulcers, n/v. Utility: Treat rheumatoid arthritis (off-label use). Special Features:

Absorption: Poorly absorbed in GI tract. Distribution: GI tract Metab.: Hydrolyzed to active form by intest. bacteria. Excretion, t_: feces Toxicity/S.E.s: Interferes w/normal flora → ↓ vit. K synth. Utility: Active in bowel lumen. Used prior to surgery to reduce microbe population. Treat inflammatory bowel disease, rheumatoid arthritis. Special Features: Broken down in intestines to liberate 5-aminosalicylate (antiinflammatory).

Name: Probenecid (Benemid) Class: Anti-Gout Agent (Uricosuric Agent) Mech.: Blocks proximal tubular reabsorption of uric acid. Absorption: Dist.: Metab.: Excretion, t_: Reabsorbed by renal tubules & metabolized slowly. Toxicity/S.E.s: GI irritation (not severe). Skin rash. Rare aplastic anemia. Utility: Treat gout via increased urinary excretion of uric acid. Blocks tubular secretion of penicillin; may be used to increase penicillin levels. Special Features: At low doses, probenecid blocks proximal tubule secretion of uric acid.

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Name: Sulfinpyrazone (Anturane) Class: Anti-Gout Agent (Uricosuric Agent) Mech.: Blocks proximal tubular reabsorption of uric acid. Absorption: Dist.: Metab.: Excretion, t_: Rapidly excreted by the kidneys. Toxicity/S.E.s: GI irritation (not severe). Skin rash. Rare aplastic anemia. Utility: Treat gout via increased urinary excretion of uric acid. Special Features: At low doses, sulfinpyrazone blocks proximal tubule secretion of uric acid.

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Name: Allopurinol (Zyloprim) Class: Anti-Gout Agent Mech.: Inhibits xanthine oxidase → ↓ production of uric acid. Absorption: Well absorbed orally. Dist.: Metab.: Metab. by xanthine oxidase to a longer acting active metabolite. Excretion, t_: Toxicity/S.E.s: GI intolerance, skin rash. Drug Interactions: Inhib. metab. of oral anticoagulants. Xanthine oxidase inactivates 6-mercaptopurine & azathioprine (cancer chemotherapeutic drugs). ∴ doses must be lowered when patient takes allopurinol. Utility: Treat chronic tophaceous gout, gout patients w/high excretion of uric acid, patients who cannot use probenecid or sulfinpyrazone, recurrent renal uric acid stones, renal impairment, grossly elevated serum acid concentrations (>13 mg/dL). Use also w/cancer chemotherapy to prevent urate nephropathy. Special Features:

Name: Colchicine Class: Anti-Gout Agent

Name: Acetaminophen (Tylenol) Class: Para-aminophenol (OTC) Mech.: Weak inhib. of peripheral prostaglandin synth. More effective CNS cyclooxygenase inhib. → antipyretic and analgesic properties. Absorption: Oral → rapid & complete w/peak in 30-60 min. Not a weak acid. Dist.: Dist. throughout body fluids. Protein binding (20-50%) not significant. Metab.: No zero-order kinetics. Phase II conjug. w/glucuronic acid & sulfate. Phase I oxid. → N-acetyl-benzoquinoneimine. Reacts w/sulfhydryl groups, but normally inactivated by glutathione (except in overdose). Excretion, t_: Majority excreted as conjug. metabolites in urine. Not related to urine pH. 2 hr. Toxicity/S.E.s: Overdose → depletion of hepatic glutathione → rxn. w/sulfhydryl groups of hepatic proteins → hepatic necrosis. Also renal tubular necrosis. Treatment w/N-acetylcysteine w/in 10 hr. of overdose can be life-saving. Utility: Analgesic and antipyretic efficacies comparable to aspirin. Special Features: Para-aminophenol prototype. Often used w/other analgesics (e.g., Tylenol + Codeine). Weak peripheral inhib. → weak antiinflammatory activity. No urocosuric or anti-platelet effects.

Name: Phenacetin Class: Para-aminophenol Mech.: Converted to acetaminophen. Weak inhib. of peripheral prostaglandin synth. More effective CNS cyclooxygenase inhib. → antipyretic and analgesic properties. Absorption: Oral → rapid & complete. Not a weak acid. Dist.: Dist. throughout body fluids. Protein binding (20-50%) not significant. Metab.: No zero-order kinetics. Phase II conjug. w/glucuronic acid & sulfate. Phase I oxid. → Nacetyl-benzoquinoneimine. Reacts w/sulfhydryl groups, but normally inactivated by glutathione (except in overdose). Excretion, t_: Majority excreted as conjug. metabolites in urine. Not related to urine pH. Toxicity/S.E.s: Nephropathy assoc. w/chronic use. Overdose → depletion of hepatic glutathione → rxn. w/sulfhydryl groups of hepatic proteins → hepatic necrosis. Also renal tubular necrosis. Treatment w/N-acetylcysteine w/in 10 hr. of overdose can be life-saving. Utility: Analgesic and antipyretic efficacies comparable to aspirin. Special Features: No longer prescribable in US due to renal toxicity. Weak peripheral inhib. → weak anti-inflammatory activity. No urocosuric or anti-platelet effects.

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Mech.: Binds to tubulin → inhib. of leukocyte migration & phagocytosis → ↓ inflamm. response. Absorption: Rapidly absorbed orally. Dist.: Metab.: Excretion, t_: Urine & feces. Toxicity/S.E.s: GI intolerance (n/v/d). Utility: Treat acute gout attacks. Use to prevent acute attacks while initiating allopurinol or probenecid therapy. Special Features: Not analgesic. No effect on uric acid production or excretion.

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Name: Cyclosporine (Sandimmune) Class: Immunosuppressant Mech.: Binds to calmodulin and a cytoplasmic cytophilin → selective inhib. of transcription of IL-2 gene → inhib. of IL-2 prod. & release from T4 cells, inhib. of proliferation of T8 cells, block of T4 activation of B cells. Absorption: Oral → highly variable and incomplete absorption. Dist.: Large Vd. Binds in tissues. 60-70% contained in RBCs. Metab.: Extensive hepatic metab involving cyt. P450 enzymes. 17 metabolites known. Drug levels monitored by RIA or HPLC. Excretion, t_: Biliary excretion, minor renal excretion. Toxicity/S.E.s: Nephrotoxicity (main toxicity), hepatotoxicity, hirsutism, gingival hyperplasia, neurotoxicity, altered coagulability. But little (if any) bone marrow suppression. Drug interactions—rifampin & phenobarbital → induction of hepatic metab. Erythromycin → inhib. of hepatic metab. Ketoconazole & amphotericin → ↓ clearance. Utility: Prolong organ transplants (1° use). Suppress cell-med. diseases. Possible benefit w/early treatment of IDDM. Special Features:

Name: OKT3 (Muromonab-CD3) Class: Immunosuppressant Mech.: Opsonizes T cells, modulates CD3 antigen recognition complex on T cells, blocks CTL killer function. Absorption: IV Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Chills, fever, thrombocytopenia, erythema, pruritis, hypersensitivity rxns, anti-OKT3 antibody production (∴ only given for 1-2 weeks). Utility: Prevent or reverse acute allograft rejection. Special Features: Murine monoclonal antibody against CD3 on T cells.

Name: Prednisone Class: Corticosteroid (Immunosuppressant)

Name: Methylprednisone Class: Corticosteroid (Immunosuppressant)

Mech.: Inhib. of IL-1 & TNF synth/release from Mφs → ↓ activation of T cells and Mφs, ↓ PMN fxn, ↓ T cell-dependent Ab production, ↓ complement activity, ↓ activity & release of kinins. Absorption: Oral Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Suppressed pituitary adrenal fxn, hypertension, weight gain, peptic ulcer, GI bleeding, euphoric personality changes, cataracts, hyperglycemia. Utility: Immunosuppression. Primarily employed to induce remission in patients w/acute lymphocytic leukemia, and for treatment of lymphomas. Treat hypercalcemia due to vit. D intox., sarcoidosis, or specific cancers (e.g., lymphoproliferative) (30-60 mg/d). Special Features:

Mech.: Inhib. of IL-1 & TNF synth/release from Mφs → ↓ activation of T cells and Mφs, ↓ PMN fxn, ↓ T cell-dependent Ab production, ↓ complement activity, ↓ activity & release of kinins.

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Absorption: Parenteral Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Suppressed pituitary adrenal fxn, hypertension, weight gain, peptic ulcer, GI bleeding, euphoric personality changes, cataracts, hyperglycemia. Utility: Immunosuppression. Primarily employed to induce remission in patients w/acute lymphocytic leukemia, and in treatment of lymphomas. Special Features:

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Name: Azathioprine (Imuran) Class: Immunosuppressant (Antimetabolite)

Name: Cyclophosphamide (Cytoxan) Class: Immunosuppressant (Alkylating Agent) (Cancer Chemotherapeutic Agent)

Mech.: Converted to 6-mercaptopurine (thiol analog of hypoxanthine) → inhib. of purine synth. → cytotoxicity to dividing cells → ↓ lymphocyte proliferation → inhib. of cellular and humoral immunity.

Mech.: Activated via hepatic P450 metabolism → phosphoramide mustard. Phosphoramide mustard alkylates DNA → cytotoxicity to dividing cells.

Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Bone marrow depression (main toxicity), n/v/d, hepatotoxicity. Utility: Primarily used in maintenance of remission in acute lymphoblastic leukemia. Special Features:

Name: Antilymphocyte Globulin (ALG) Class: Immunosuppressant Mech.: Polyclonal antibody to human lymphocytes (not selective to CD3) → destruction and inactivation of lymphocytes. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Chills, fever, thrombocytopenia, erythema, pruritis, hypersensitivity rxns, anti-ALG antibody production (∴ only given for 1-2 weeks). Utility: Prevent or reverse acute allograft rejection. Special Features:

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Absorption: Oral Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Bone marrow depression (esp. leukocytosis), hemorrhagic cystitis (may → bladder fibrosis), n/v/d, alopecia, amenorrhea, testicular atrophy, sterility. Possible secondary malignancies years later. Utility: Cancer chemotherapy, nephrotic syndrome, intractable rheumatoid arthritis. Special Features: Therapeutic effect independent of level of P450 activity.

Name: G-CSF (Filgrastim) Class: Immunostimulant Mech.: Promotes growth & differentiation of granulocyte precursors. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Bone pain, fever, anti-CSF antibodies. Utility: Restore hematopoiesis (FDA-approved to treat neutropenia), augment host defenses, esp. after cancer therapy. Special Features:

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Name: GM-CSF (Sargramostim) Class: Immunostimulant Mech.: Stim. bone marrow production of precursors to PMNs, monocytes, platelets. Also activates PMNs, eosinophils, and monocytes. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Fever, dermatologic rxns, splenomegaly. Utility: FDA-approved to increase myeloid recovery rate after bone marrow transplantation. Also used for hematological reconstitution after autologous bone marrow transplants and treatments w/bone marrow cytotoxic drugs. Special Features: Greater severity of immunologic S.E.s than w/G-CSF.

Name: Erythropoietin (Epoetin Alfa, Epogen) Class: Immunostimulant Mech.: Stim. division/differentiation of erythroid progenitors in bone marrow. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Usu. well-tolerated. Low incidence of hypertension, headache, seizures. Rare hypersensitivity rxns. Utility: Treat anemia assoc. w/chronic renal failure, AZT therapy, cancer and chemotherapy. Supplemental iron eventually required in therapy. Special Features: Manufactured by recombinant DNA technology. Identical to human erythropoietin.

Name: Interferon α Class: Immunostimulant

Name: Interferon β Class: Immunostimulant

Mech.: Binds to cell-surface receptors → inhib. of viral replication, inhib. of cell proliferation. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Fever w/chills; dose-related leukopenia, thrombocytopenia; fatigue, malaise, anorexia, weight loss, alopecia, transient elevation of liver enzymes. High doses may → transient & reversible nephrotoxicity.

Mech.: Binds to cell-surface receptors → inhib. of viral replication, inhib. of cell proliferation. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Fever w/chills; dose-related leukopenia, thrombocytopenia; fatigue, malaise, anorexia, weight loss, alopecia, transient elevation of liver enzymes. High doses may → transient & reversible nephrotoxicity. Utility: Used to treat for chronic hepatitis B, virally induced tumors, recurrent varicella zoster, HSV keratitis, Kaposi’s sarcoma, hairy cell leukemia, cutaneous T cell lymphoma. Special Features: Produced by fibroblasts. Interferon production is induced by dsRNA (poly I:C), ampligen (mismatched nucleotides), LPS.

Utility: IFN α2A is approved for mgt. of hairy cell leukemia. Also useful for chronic hepatitis B, virally induced tumors, recurrent varicella zoster, HSV keratitis, Kaposi’s sarcoma, cutaneous T cell lymphoma. Special Features: Produced by mononuclear leukocytes. Interferon production is induced by dsRNA (poly I:C), ampligen (mismatched nucleotides), LPS.

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Name: Interferon γ Class: Immunostimulant

Name: Bacillus Calumet-Guerin (BCG) Class: Immunostimulant

Mech.: Binds to cell-surface receptors → activation of NK cells and Mφs, promotion of conversion to TH1 cells. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Fever w/chills; dose-related leukopenia, thrombocytopenia; fatigue, malaise, anorexia, weight loss, alopecia, transient elevation of liver enzymes. High doses may → transient & reversible nephrotoxicity. Utility: Used to treat for chronic hepatitis B, virally induced tumors, recurrent varicella zoster, HSV keratitis, Kaposi’s sarcoma, hairy cell leukemia, cutaneous T cell lymphoma. Special Features: Produced by memory TH1 cells and NK cells. Interferon production is induced by dsRNA (poly I:C), ampligen (mismatched nucleotides), LPS.

Mech.: Viable strain of Mycobaterium bovis. Enhances Mφ activity, promotes Mφ tumoricidal activity. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Utility: Treat bladder carcinoma and melanomas. Special Features:

Name: Misoprostol (Cytotec) Class: Gastric Protectant (Prostaglandin) Mech.: Analog of prostaglandin E1. Inhib. secretion of HCl. Stimulates secretion of mucus & HCO3 (cytoprotective). Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Diarrhea, nausea. Produces uterine contractions. ∴ c/i during pregnancy. Utility: Only agent approved for prevention of gastric ulcers induced by NSAIDs. Less effective than H2 antagonists for acute treatment of peptic ulcers. Special Features:

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How, if some day or night a demon were to sneak after you into your loneliest loneliness and say to you, “This life as you now live it and have lived it, you will have to live once more and innumerable times more; and there will be nothing new in it, but every pain and every joy and every thought and sigh and everything immeasurably small or great in your life must return to you - all in the same succession and sequence - even this spider and this moonlight between the trees, and even this moment and I myself. The eternal hourglass of existence is turned over and over, and you with it, a dust grain of dust.” Would you not throw yourself down and gnash your teeth and curse the demon who spoke thus? Or did you once experience a tremendous moment when you would have answered him, “You are a god, and never have I heard anything more godly.” If this thought were to gain possession of you, it would change you, as you are, or perhaps crush you. The question in each and every thing, “Do you want this once more and innumerable times more?” would weigh upon your actions as the greatest stress. Or how well disposed would you have to become to yourself and to life to crave nothing more fervently than this ultimate eternal confirmation and seal? - Nietzsche

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Name: Mannitol Class: Diuretic (Non-Metabolized Osmotic Diuretic)

Name: Acetazolamide (Diamox) Class: Diuretic (Carbonic Anhydrase Inhibitor)

Mech.: Filtered into tubule space → ↑↑ tubular fluid osmolality → ↓ fluid reabsorption → ↑ excretion of water and some Na+ .

Mech.: Inhib. of CA → ↓ reabsorption of NaHCO3 in prox. tubule. K+ is exchanged for Na+ in distal tubule. Net = ↑ in urinary HCO3-, K+ , and water excretion. Absorption: Oral. Takes effect in 30 min. Dist.: Metab.: Excretion, t_: 13 hr. Toxicity/S.E.s: Metabolic acidosis, hypokalemia. C/i—cirrhosis.

Absorption: IV only (oral → osmotic diarrhea). Takes effect in 10 min. Dist.: Metab.: Excretion, t_: 1.2 hr. Toxicity/S.E.s: ↑ plasma osmolality. If GFR is reduced (e.g., renal failure or CHF), mannitol stays in ECF → water movement from cells to ECF → potential production/exacerbation of heart failure and hyponatremia. C/i—CHF, renal failure. Utility: Prophylaxis against renal dysfunction (e.g., in major surgical procedures). Special Features:

Name: Furosemide (Lasix) Class: Diuretic (Loop Diuretic) Mech.: Blocks the Na+/K+/Cl- co-transporter in the apical membrane of the thick ascending limb of Henle’s loop → ↑ excretion of urinary water, Na+, K+, Ca2+, & Mg2+. Also causes venous and renal vasodilation. Absorption: Oral, IV. Takes effect in 20 min. Dist.: Metab.: Excretion, t_: 1-1.5 hr. Shorter duration than thiazides. Toxicity/S.E.s: Hypokalemia (esp. dangerous if pt. is on digitalis), Ca2+ & Mg2+ depletion, metabolic alkalosis, volume contraction, mild hyperglycemia, thiazide-like lipid changes, sulfonamide allergy cross-rxn, ototoxicity. C/i—pts. susceptible to volume contraction from excessive diuresis (e.g., elderly), and pts. susceptible to problems w/hypokalemia (e.g., cirrhosis, digitalis). Adverse rxn w/lithium, aminoglycosides. Altered doses of anti-diabetic agents required. Utility: Diuresis for hypertension when a short-acting diuretic is indicated. Treat HTN refractory to thiazides. Very useful in conditions refractory to less potent diuretics (e.g., CHF, renal insufficiency, nephrotic synd.). Treat hypercalcemia. Special Features: Most potent diuretics available. Can cause excretion of up to 20% of filtered Na+.

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Utility: Treat glaucoma and ↑ CNS pressure. Alkalinize urine. Prevent altitude sickness. Diuresis. Special Features: Relatively weak diuretic. Generally prescribed for nondiuretic purposes. Effectiveness reduced w/continued therapy because plasma [HCO3-] falls.

Name: Bumetanide (Bumex) Class: Diuretic (Loop Diuretic) Mech.: Blocks the Na+ /K+ /Cl- co-transporter in the apical membrane of the thick ascending limb of Henle’s loop → ↑ excretion of urinary water, Na+ , K+ , Ca2+, & Mg2+. Also causes venous and renal vasodilation. Absorption: Oral, IV. Takes effect in 20 min. Dist.: Metab.: Excretion, t_: 1-1.5 hr. Toxicity/S.E.s: Hypokalemia (esp. dangerous if pt. is on digitalis), Ca2+ & Mg2+ depletion, metabolic alkalosis, volume contraction, mild hyperglycemia, sulfonamide allergy cross-rxn, ototoxicity. C/i—pts. susceptible to volume contraction from excessive diuresis (e.g., elderly), and pts. susceptible to problems w/hypokalemia (e.g., cirrhosis, pts. taking digitalis). Utility: Diuresis for hypertension when a short-acting diuretic is indicated. Very useful in conditions refractory to less potent diuretics, including CHF, renal insufficiency, and nephrotic synd. Also used to treat hypercalcemia. Special Features: Most potent diuretics available. Far more potent than furosemide. Can cause excretion of up to 20% of filtered Na+ .

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Name: Ethacrynic Acid (Edecrin) Class: Diuretic (Loop Diuretic) Mech.: Blocks the Na+ /K+ /Cl- co-transporter in the apical membrane of the thick ascending limb of Henle’s loop → ↑ excretion of urinary water, Na+ , K+ , Ca2+, & Mg2+. Also causes venous and renal vasodilation. Absorption: Oral, IV. Takes effect in 20 min. Dist.: Metab.: Excretion, t_: 1-1.5 hr. Toxicity/S.E.s: Hypokalemia (esp. dangerous if pt. is on digitalis), Ca2+ & Mg2+ depletion, metabolic alkalosis, volume contraction, mild hyperglycemia, ototoxicity. C/i—pts. susceptible to volume contraction from excessive diuresis (e.g., elderly), and pts. susceptible to problems w/hypokalemia (e.g., cirrhosis, pts. taking digitalis). Utility: Diuresis for hypertension when a short-acting diuretic is indicated. Very useful in conditions refractory to less potent diuretics, including CHF, renal insufficiency, and nephrotic synd. Also used to treat hypercalcemia. Special Features: More ototoxic than other loop diuretics. Most potent diuretics available. Can cause excretion of up to 20% of filtered Na+ .

Name: Hydrochlorothiazide (Hydrodiuril) Class: Diuretic (Thiazide) Mech.: Inhib. Na+ & Cl- transport in the cortical thick ascending limb and the early distal tubule → ↑ NaCl and water excretion, & ↓ excretion of Ca2+ and uric acid. Absorption: Oral → good absorption. Takes effect in 1 hr. Dist.: Metab.: Excretion, t_: Short duration of action. Toxicity/S.E.s: Hypokalemia, hyponatremia, hyperuricemia, weakness, hypercalcemia, metabolic alkalosis, postural hypotension, hypercholesterolemia, hypertriglyceridemia, hyperglycemia (in patients w/DM), and rare hypersensitivity rxns. C/i—pts susceptible to problems with hypokalemia (cirrhosis, pts on digitalis), hyperuricemia (gout), or hypercalcemia. Adverse rxns w/digitalis, lithium. Altered doses of anti-diabetic agents required. Long-term NSAID use may decrease anti-HTN effects. Utility: Treat hypertension, CHF, nephrotic synd., other Na+ -retaining states. Reduce Ca2+ excretion (e.g., prevention of kidney stones). Special Features: Most commonly prescribed class of diuretics. Most frequently used anti-HTN class of agents. Milder diuretic action than loop diuretics. Rel. ineffective in renal insuff.

Name: Chlorthalidone (Hygroton) Class: Diuretic (Thiazide) Mech.: Inhib. Na+ & Cl- transport in the cortical thick ascending limb and the early distal tubule → ↑ NaCl and water excretion, & ↓ excretion of Ca2+ and uric acid.

Name: Spironolactone (Aldactone) Class: Diuretic (Potassium Sparing Diuretic) (Aldosterone Antagonist)

Absorption: Oral → good absorption. Takes effect in 1 hr. Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Hypokalemia, hyponatremia, hyperuricemia, hypercalcemia, metabolic alkalosis, postural hypotension, hyperglycemia (in patients w/DM), and rare hypersensitivity rxns. C/i—pts susceptible to problems with hypokalemia (cirrhosis, pts on digitalis), hyperuricemia (gout), or hypercalcemia. Utility: Treat hypertension, CHF, nephrotic synd., other Na+ -retaining states. Reduce Ca2+ excretion (e.g., prevention of kidney stones). Special Features: Most commonly prescribed class of diuretics. Milder diuretic action than loop diuretics. Rel. ineffective in renal insuff.

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Mech.: Competitive inhib. of aldosterone → block of aldost.-stim. Na+ reabsorption and K+ /H+ excretion in late distal tubule and collecting duct. Also reduces aldost.-stim. ammoniagenesis throughout the nephron. Absorption: Oral. Takes up to 2 days to be effective. Dist.: Metab.: Hepatic. Excretion, t_: 20 hr. Toxicity/S.E.s: Hyperkalemia, gynecomastia, amenorrhea. Absolutely contraindicated w/hyperkalemia. Utility: Most efficacious in pts. w/high plasma levels of aldosterone (e.g., 1° hyperaldosteronism due to an adrenal tumor or hyperplasia; 2° hyperaldost. due to cirrhosis, etc.). Special Features: Only diuretic that acts through the blood side of the tubule. Rel. weak diuretic.

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Name: Metolazone (Mykrox) Class: Diuretic (Thiazide-Like) Mech.: Inhib. Na+ & Cl- transport in the cortical thick ascending limb and the early distal tubule → ↑ NaCl and water excretion, & ↓ excretion of Ca2+ and uric acid. Absorption: Oral → good absorption. Takes effect in 1 hr. Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Hypokalemia, hyponatremia, hyperuricemia, hypercalcemia, metabolic alkalosis, postural hypotension, hyperglycemia (in patients w/DM), and rare hypersensitivity rxns. C/i—pts susceptible to problems w/hypokalemia (cirrhosis, pts on digitalis), hyperuricemia (gout), or hypercalcemia. Utility: The only distal nephron diuretic efficacious in patients w/severe renal insufficiency. Treat hypertension, CHF, nephrotic synd., other Na+ retaining states. Reduce Ca2+ excretion (e.g., prevention of kidney stones). Special Features: Strongest inhib. of Na+ & water reabsorption of the thiazide and thiazide-like diuretics. Often given in comb. w/a loop diuretic. Milder diuretic action than loop diuretics.

Name: Amiloride (Midamor) Class: Diuretic (Potassium Sparing Diuretic) Mech.: Inhib. Na+ channel in the apical membrane of the late distal tubule and collecting duct → block of electrochemical gradient that drives K+ & H+ secretion → diuresis & ↓ excretion of K+ & H+ . Absorption: Oral Dist.: Metab.: Excretion, t_: 1° = kidney. 6 hr. Toxicity/S.E.s: Hyperkalemia (most severe), n/v (most common), metabolic acidosis. Hyponatremia may occur in old folks. Absolutely contraindicated with hyperkalemia. Utility: Usu. given w/another diuretic (often thiazide or loop). Combination usu. → normal K+ excretion.

Name: Triamterene (Dyrenium) Class: Diuretic (Potassium Sparing Diuretic) Mech.: Inhib. Na+ channel in the apical membrane of the late distal tubule and collecting duct → block of electrochemical gradient that drives K+ & H+ secretion → diuresis & ↓ excretion of K+ & H+ . Weak anti-HTN activity. Absorption: Oral Dist.: Metab.: Excretion, t_: 1° = kidney. 3 hr. Toxicity/S.E.s: Hyperkalemia (most severe), n/v (most common), metabolic acidosis. Hyponatremia may occur in old folks. Absolutely contraindicated with hyperkalemia. Adverse rxns w/lithium, ACE inhibitors. Rare renal failure w/NSAIDs. Utility: Usu. given w/another diuretic (often thiazide or loop). Combination usu. → normal K+ excretion. Used to prevent or correct hypokalemia, and to avoid K+ depletion in pts. on digitalis. Special Features: Rel. weak diuretic.

Type of my disciples. - To those human beings who are of any concern to me I wish suffering, desolation, sickness, ill-treatment, indignities - I wish that they should not remain unfamiliar with profound selfcontempt, the torture of self-mistrust, the wretchedness of the vanquished: I have no pity for them, because I wish them the only thing that can prove today whether one is worth anything or not - that one endures. - Nietzsche

Special Features: Rel. weak diuretic.

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Name: Estradiol (Estrace) Class: Estrogen Mech.: Diffuses across cell membranes and binds to cytoplasmic receptor proteins. Complex enters nucleus and interacts w/DNA to initiate RNA synthesis. Stimulates development of the endometrial lining, maintains normal structure of skin and blood vessels in E, antagonizes PTH effects on bone, reduces motility of the bowel, enhances coagulability of blood, increases HDL, decreases LDL. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: May increase risks of breast and endometrial cancer. Nausea/vomiting. Utility: Postmenopausal estrogen replacement therapy to treat hot flashes, atrophic vaginitis, and urethral changes, and to prevent osteoporosis and cardiovascular disease. Special Features: Usu. combined with a progestin to reduce the risk of endometrial carcinoma. Only useful prophylactically for osteoporosis,.

Name: Conjugated estrogens (Premarin) Class: Estrogen Mech.: Diffuses across cell membranes and binds to cytoplasmic receptor proteins. Complex enters nucleus and interacts w/DNA to initiate RNA synthesis. Stimulates development of the endometrial lining, maintains normal structure of skin and blood vessels in E, antagonizes PTH effects on bone, reduces motility of the bowel, enhances coagulability of blood, increases HDL, decreases LDL. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Increased risk of breast and endometrial cancer. Utility: Postmenopausal estrogen replacement therapy to treat hot flashes, atrophic vaginitis, and urethral changes, and to prevent osteoporosis and cardiovascular disease. Special Features: Usu. combined with a progestin to reduce the risk of endometrial carcinoma. Only useful prophylactically for osteoporosis. Less first-pass metab. than estradiol → more effective oral administration.

Name: Norethindrone (Norlutine) Class: Oral Contraceptive (Progestin-Only) (Mini-Pill)

Name: Levonorgestrel (Norplant) Class: Long-Acting Contraceptive (Progestin-Only)

Mech.: Doesn’t always inhibit ovulation. Produces changes in cervical mucus → block of sperm penetration. Absorption: Oral Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: High incidence of abnormal bleeding. Headache, depression. Utility: Contraception, esp. in patients c/i for estrogen therapy. Special Features: Less effective than estrogen-progestin combination pills. None of the cardiovascular toxicity of the combination pill.

Mech.: Doesn’t always inhibit ovulation. Produces changes in cervical mucus → block of sperm penetration. Absorption: Subcutaneous implant Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Irregular menstrual bleeding and headaches. Utility: Contraception, esp. in patients c/i for estrogen therapy. Special Features: Cheaper than oral contraceptives, completely reversible, and good for 5 years. Probably the most effective reversible method of contraception available. None of the cardiovascular toxicity of the combination pill.

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Name: Norgestrel (Ovrette) Class: Oral Contraceptive (Mini-Pill) (Low-Dose Progestin) Mech.: Doesn’t always inhibit ovulation. Produces changes in cervical mucus → block of sperm penetration. Absorption: Oral Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: High incidence of abnormal bleeding. Headaches, depression. Utility: Contraception, esp. in patients c/i for estrogen therapy. Special Features: Less effective than estrogen-progestin combination pills. None of the cardiovascular toxicity of the combination pill.

Name: Morning-After Pill (Ovral, The Pill, etc.) Class: Oral Contraceptive (Estrogen/Progestin Combination) Mech.: Blocks nidation by producing an unfavorable endometrium. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Breast fullness, depression, dizziness, edema, headache, n/v, cardiovascular disease (esp. in smokers over age 35). C/i in presence of cerebrovascular and thromboembolic disease, estrogen-dependent neoplasms, liver disease, and migraine headache. Utility: Post-coital contraceptive. Usu. ~99% effective if admin. w/in 72 hours. Special Features:

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Name: The Pill (Various) Class: Oral Contraceptive (Estrogen/Progestin Combination) Mech.: Blocks ovulation, suppresses endometrial growth, produces changes in cervical mucus → block of sperm penetration. Absorption: Oral. Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Breakthrough bleeding, amenorrhea, water retention, headache, breast fullness, depression, dizziness, edema, headache, n/v, weight gain, acne, cardiovascular disease (esp. in smokers over age 35). Absolute C/Is—thromboembolic disorder, CVA, CAD, ↓ liver fxn, hepatic adenoma, estrogen-dependent cancer (e.g., breast, endometrium), pregnancy, undiagnosed vaginal bleeding, tobacco use over age 35. Relative C/Is—migraine headaches, hypertension, leiomyomata, diabetes mellitus or prev. gestational diabetes, elective surgery, seizures or anticonvulsant use, obstructive jaundice in pregnancy, sickle cell disease, gall bladder disease. Utility: Contraception, dysmenorrhea, prophylaxis against endometriosis. Special Features: Decreases the risks of endometrial and ovarian cancer and benign breast disease.

Name: Medroxyprogesterone (Depo-Provera) Class: Long-Acting Contraceptive (Progestin-Only) Mech.: Doesn’t always inhibit ovulation. Produces changes in cervical mucus → block of sperm penetration. Absorption: IM Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Irregular menstrual bleeding, headaches, depression. Drug cannot be removed to alleviate side effects. Utility: Contraception, esp. in patients c/i for estrogen therapy. Special Features: None of the cardiovascular toxicity of the combination pill.

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Name: Thalidomide Class: Teratogen With Immediate Developmental Effects Mech.:. Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Embryonic exposure between weeks 4-7 of gestation → ↑↑ risk of birth defects, esp. phocomelia. Paternal use of thalidomide can also result in serious birth defects. Risk only in first trimester. Utility: Currently used in treatment of leprosy and AIDS. Special Features: Previously widely used in Europe as a sedative-hypnotic with the result of ~8,000 babies with phocomelia.

Name: Diethylstilbestrol (DES) Class: Teratogen With Delayed Developmental Defects Mech.: Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Female fetuses exposed to diethylstilbestrol are at increased risk for vaginal adenosis and clear cell vaginal adenocarcinoma after puberty. Risk present in all trimesters. Utility: Special Features: Previously commonly used to treat pregnant women who were threatening spontaneous abortion.

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Name: Isotretinoin (Accutane) Class: Teratogen With Immediate Developmental Effects Mech.: Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: Extremely high risk of congenital anomalies. Problem for pimply pregnant people. Risk present in all trimesters. Utility: Used to treat severe, intractable acne. Special Features:

Name: Ethanol Class: Teratogen With Immediate and Delayed Developmental Effects Mech.: Absorption: Dist.: Metab.: Excretion, t_: Toxicity/S.E.s: High risk of fetal alcohol syndrome. Risk present in all trimesters. Utility: Special Features:

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