Antifungal and Antiviral Drugs

Question 1

Amantidine and Rimantidine- MOA, A, D, E, Spectrum/Uses, Adverse Rxns

Answer 1

Inhibit viral uncoating by block of viral M2 proton channel. Good po. Accumulates in lung. Renal [A] and Hepatic [R] Elimination. Prophylaxis/ Treatment of Influenza A (emergence of resistance has been high). GI upset, insomnia, confusion, headache (decrease CNS effects with rimantidine)

Question 2

Oseltamivir, Zanamivir, and Peramivir- MOA, A, E, Spectrum/Uses, Adverse Rxns

Answer 2

Inhibit viral neuroaminidase to decrease viral budding (decrease infectivity). Oral [O], Inhalation [Z], IV [P]. All renally excreted. Prophylaxis/ Treatment of influenza A, B, C. Oseltamivir: n/v. Zanamivir: bronchospasm.

Question 3

Acyclovir, Valacyclovir, Penciclovir, Famciclovir- MOA, A, Bioavailability, Spectrum/Uses, Adverse Rxns

Answer 3

Phosphorylated by viral thymidine kinase to inhibit viral DNA polymerase chain plus chain termination. [A]: topical, oral, IV. [A: 15-30% Cp, VAL/FAM: 80% Cp (prodrugs)]. [P]: topical only. HSV-1/ HSV-2 (mucosal, genital, encephalitis), and varicella-zoster at higher doses. Minor toxicities (headache, n/v), higher levels with valacyclovir may increase risk of CNS/ renal side effects.

Question 4

Docosanol (OTC)- MOA, A, Spectrum/Uses, Adverse Rxns

Answer 4

Inhibits fusion between plasma membrane and HSV envelope. Topically applied 5x daily. HSV-1 labialis. Well tolerated.

Question 5

Gancyclovir (Valacyclovir valyl ester prodrug)- MOA, A, D, E, Spectrum/Uses, Adverse Rxns

Answer 5

Phosphorylated by viral thymidine kinase to active form that inhibits viral DNA polymerase. Poor po (good w/ valganciclovir), distributes to CNS, renal excretion. HSV, VZV, CMV (more active butmore toxic than acyclovir). Sight threatening CMV retinitis. Bone marrow depression, CNS (HA, behavioral changes)

Question 6

Cidofovir- MOA, A, Spectrum/Uses, Adverse Rxns

Answer 6

Nucleotide analog, phosphorylated to active form by host kinases, inhibits viral DNA polymerase. Long intracellular t1/2 (17-35h), given IV weekly/ biweekly. Active against many DNA viruses CMV infections (if resistant to ganciclovir/ foscarnet). Nephrotoxicity (decreased by probenecid use), rash in HIV pts.

Question 7

Foscarnet- MOA, A, Spectrum/Uses, Adverse Rxns

Answer 7

Pyrophosphate Analog, (No activation step!), inhibits viral/DNA/RNA poly and RT. Poor po, requires continous infusion. CMV infections (GAN resistant) acyclovir resistant herpes infections HIV (2nd line). Renal impairment, severe n/v, electrolyte imbalnce (esp. hypocalcemia).

Question 8

Ribavirin- MOA, Pharmacokinetics, Spectrum/Uses, Adverse Rxns

Answer 8

Triphosphorylated to active form, inhibits IMP dehydrogenase, viral RNA-dep RNA polymerase. Aerosol administration, well absorbed-orally, long intracellular t1/2. RSV (inh), hepatitis C (oral w/ interferon). Low aerosol toxicity, but teratogen, systemic toxicity includes anemia, bone marrow depression.

Question 9

Amphotericin- MOA, A, E, Spectrum/Uses, Adverse Rxns

Answer 9

Binds to ergosterol, forming pores in membranes with loss of vital intracellular constituents. IV or topical only, slow excretion by kidney plus hepatobiliary (t1/2 = 15d). Broad spectrum, choice for life threatening systemic infections. Acute: fever and chills on infusionl nephrotoxicity (80%), anemia.

Question 10

Nystatin- MOA, Pharmacokinetics, Spectrum/Uses, Adverse Rxns

Answer 10

Binds to ergosterol, forming holes in membranes with loss of vital intracellular constituents. Topical only (poor po). Superficial Candidal infections. Well tolerated given topically, mild GI upset (if swallowed).

Question 11

Caspofungin- MOA, Pharmacokinetics, Spectrum/Uses, Adverse Rxns

Answer 11

Inhibits synthesis of cell wall component, disrupting assembly. IV infusion only, levels decrease by P450 inducers. Aspergillosis (if refractory to ampho B). Infusion related symptoms (via histamine: rash, pruritus, n/v).

Question 12

Triazoles- MOA and the 3 Triazole drugs

Answer 12

Inhibit P450 ergosterol synthesis, altering membrane permeability, but more selective inhibition of fungal P450 compared to Imidazole. Fluconazole, Itraconazole, Terconazole.

Question 13

Fluconazole- A, D, E, Spectrum/Uses, Adverse Rxns

Answer 13

IV/po, enters CNS, renal excretion. Oopharyngeal/esophageal candiasis, vulvovaginal candidiasis (single dose), cryptococcal meningitis. Well tolerated (GI upset) lesser effecton CYP450 metabolism.

Question 14

Itraconazole- A, E, Spectrum/Uses, Adverse Rxns

Answer 14

IV/po, hepatic metabolism. Superficial dermatophytosis, onychomycosis. n/v, diarrhea, headache, inhibits CYP450 drug metabolism.

Question 15

Teraconazole- A, Spectrum/Uses

Answer 15

Topical only. Vulvovaginal candiasis.

Question 16

Imidazoles- MOA and the 2 Imidazole drugs

Answer 16

Inhibits P450 ergosterol synthesis, altering membrane permeability. Ketoconazole, Clotrimazole/Miconazole.

Question 17

Ketoconazole- A, E, Spectrum/Uses, Adverse Rxns

Answer 17

IV/po/topical, hepatic metabolism. Systemic infections (e.g. candiasis) (declining systemic use due to toxicity) wide use in dermotologic indications. Anorexia, n/v, heptotoxicity inhibits CYP450 drug metabolism and androgen-GC biosynthesis.

Question 18

Clotrimazole/ Miconazole- A, Spectrum/Uses

Answer 18

Topical only. Oral and vaginal candidiasis.

Question 19

Terbinafine- MOA, A, E, Spectrum/Uses, Adverse Rxns

Answer 19

Inhibits squalene oxidase reducing ergosterol synthesis. Po and topical, metabolized by hepatic P450. Onychomycosis of finger/ toe nails (po), or athlete’s foot (topical). Headache, diarrhea, rash, inhibition of CYP450.

Question 20

Flucytosine- MOA, Pharmacokinetics, Spectrum/Uses, Adverse Rxns

Answer 20

converted to 5FU in fungi: inhibits thymidylate synthetase and DNA synthesis. Well absorbed and distributed, renally eliminated (decrease dose if renal impairment). Seriousinfectionsof cryptococcosis, and candidiasis. N/v, skin rashes (prolonged use leads to bone marrow depression).

Question 21

Griseofulvin- MOA, Pharmacokinetics, Spectrum/Uses, Adverse Rxns

Answer 21

Binds to fungal microtubules, inhibiting mitosis. Poor po absorbtion, improved by microsizing particle, fatty meal. Severe dermatophytosis of skin, hair, finger/toenails. Hypersensitivity reactions, GI distress, headache, and confusion.