Antivirals

Question 1

Oseltamivir, Zanamivir

Answer 1

Inhibits neuraminidase, decreasing release of influenza A and B from infected cells

Question 2

Amantadine

Answer 2

Impairs uncoating fo the influenza A virion after host cell endocytosis.

Rarely used due to increased resistance

Question 3

Ribavirin

Answer 3

Inhibits synthesis of guanine nucleotides by competitively inhibiting inosine monophosphate dehydrogenase

Treats RSV and HCV

Toxicity: hemolytic anemia, teratogen

Question 4

Acyclovir, famciclovir, valaciclovir

Answer 4

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

Question 5

Ganciclovir

Answer 5

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

Question 6

Foscarnet

Answer 6

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

Question 7

Cidofovir

Answer 7

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)

Question 8

Clinical use of IFN-alpha

Answer 8

• Chronic HBV/HCV
• Kaposi sarcoma
• Hairy cell leukemia
• Condyloma acuminatum
• Renal cell carcinoma
• Malignant melanoma

Question 9

Clinical use of IFN-beta

Answer 9

Multiple sclerosis

Question 10

Clinical use of IFN-gamma

Answer 10

Chronic granulomatous disease

Question 11

Enfuviritide

Answer 11

HIV fusion inhibitor that binds gp41

Question 12

Maraviroc

Answer 12

HIV fusion inhibitor that binds CCR-5 on T cells/monocytes, inhibiting interaction with gp120

Question 13

Raltegravir

Answer 13

Reversibly inhibits HIV integrase

Toxicity: hypercholesterolemia

Question 14

Efavirenz, Nevirapine, Delavirdine

Answer 14

Non-nucleoside reverse transcriptase inhibitors

• Do NOT require phosphorylation
• Toxicity: rash, hepatotoxicity
  
  • Efavirenz - vivid dreams, CNS symptoms
  • Delavirdine, Efavirenz - teratogens

Question 15

Atazanavir, Darunavir, Ritonavir, other “-navirs”

Answer 15

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)

Question 16

Zidovudine, Tenofovir, Stavudine, Lamivudine, Emtricitabine, Didanosine, Abacavir

Answer 16

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)