Antivirals Flashcards
Oseltamivir, Zanamivir
Inhibits neuraminidase, decreasing release of influenza A and B from infected cells
Amantadine
Impairs uncoating fo the influenza A virion after host cell endocytosis.
Rarely used due to increased resistance
Ribavirin
Inhibits synthesis of guanine nucleotides by competitively inhibiting inosine monophosphate dehydrogenase
Treats RSV and HCV
Toxicity: hemolytic anemia, teratogen
Acyclovir, famciclovir, valaciclovir
Guanosine analogs that preferentially inhibits viral DNA polymerase by chain termination.
Requires phosphorylation by HSV/VZV thymidine kinase. No effect on latent forms of HSV/VZV.
Valacyclovir has better oral bioavailability
Famiciclovir is used for herpes zoster
Toxicity: obstructive crystalline nephropathy and acute renal failure of not adequately hydrated
Ganciclovir
Guanosine analog that preferentially inhibits viral DNA polyermase
Requires phosphorylation by CMV viral kinase
Valganciclovir has better oral bioavailability.
Toxicity: leukopenia, neutropenia, thrombocytopenia, renal toxicity
Foscarnet
Viral DNA polyermase inhibitor that binds to pyrophosphate-binding site of enzyme
Does NOT require activation by viral kinase
Treats CMV retinitis in immunocompromised patients resistant to ganciclovir. Treats acyclovir-resistant HSV
Toxicity: hypocalcemia, hypomagnesemia, nephrotoxicity
Cidofovir
Viral DNA polyermase inhibitor
Does NOT require activation by viral kinase
Treats CMV retinitis in immunocompromised patients. Treats acyclovir-resistant HSV
Toxicity: nephrotoxicity (coadminister with probenecid [uricosuric] and IV saline to decrease toxicity)
Clinical use of IFN-alpha
- Chronic HBV/HCV
- Kaposi sarcoma
- Hairy cell leukemia
- Condyloma acuminatum
- Renal cell carcinoma
- Malignant melanoma
Clinical use of IFN-beta
Multiple sclerosis
Clinical use of IFN-gamma
Chronic granulomatous disease
Enfuviritide
HIV fusion inhibitor that binds gp41
Maraviroc
HIV fusion inhibitor that binds CCR-5 on T cells/monocytes, inhibiting interaction with gp120
Raltegravir
Reversibly inhibits HIV integrase
Toxicity: hypercholesterolemia
Efavirenz, Nevirapine, Delavirdine
Non-nucleoside reverse transcriptase inhibitors
- Do NOT require phosphorylation
- Toxicity: rash, hepatotoxicity
- Efavirenz - vivid dreams, CNS symptoms
- Delavirdine, Efavirenz - teratogens
Atazanavir, Darunavir, Ritonavir, other “-navirs”
Protease inhibitors
- Inhibits HIV-1 protease (pol gene), which normally cleaves the polypeptide products of HIV mRNA into their functional parts
- Ritonavir inhibits cytochrome P-450
- Toxicity: hyperglycemia, GI intolerance, lipodystrophy, hematuria (indinavir)
Zidovudine, Tenofovir, Stavudine, Lamivudine, Emtricitabine, Didanosine, Abacavir
Nucleoside reverse transcriptase inhibitors
- Competitively inhibit nucleotide bindings to reverse transcriptase and terminate the DNA chain (lack 3’ OH group)
- All NRTIs (except Tenofovir) require phosphorylation
- Zidovudine is used to derease risk of fetal transmission
- Toxicity: bone marrow suppression (tx with G-CSF and EPO), peripheral neuropathy, lactic acidosis, rash, anemia (zidovudine), pancreatitis (didanosine)
