Acyclovir

-ovir (anti-herpetics)

MOA: herpes helps to activate the drug by first monophorphorylating via viral thymidine kinase (resistance occurs when HSV strain doesn't have it) the drug, host cell kinases then convert to triphosphate

It inhibits viral DNA polymerase b/c looks like a DNA base and causes chain termination

Uses: HSV, VZV (decreases acute neuritis in shingles but no effect on postherpetic neuralgia)

SE: crystalluria (so maintain good hydration!) & neurotoxicity

Other drugs = famciclovir, valacyclovir 

Ganciclovir

-ovir (anti-herpetic)

MOA: 1st phosphorylation is via the virus thymidine kinase (HSV) or phosphotransferase (CMV) when triphosphorylated it inhibits the viral DNA polymerase and causes chain termination

Uses: HSV, VZV, CMV (mostly used as prophylaxis/tx of CMV in AIDS pts)

SE: dose-limiting hematotoxicity (leukopenia, thrombocytopenia) crystalluria (maintain hydration)

Foscarnet

MOA: inhibits viral DNA/RNA polymerases (not an anti-metabolite though)

Uses: HSV, VZV (but > activity against acyclovir-resistant strains of HSV

SE: dose-limiting nephrotoxicity, w/ acute tubular necrosis 

Nucleoside reverse transcriptase inhibitors

Drugs: zidovudine, azidothymidine

MOA: inhibits reverse transcriptase by competing w/ natural nucleotides or by incorporation into viral DNA for chain termination

Uses: highly active antiretroviral therapy used together with protease inhibitors in HIV

DI: P450 inhibitors cause increased levels (like cimetidine, indomethacin, probenecid)

P450 inducers cause decreased levels (like rifampin)

SE: hematotoxicity (neutropenia, anemia, granulocytopenia)

Didanosine: Pancreatitis (major SE)

Zalcitabine: peripheral neuropathy

Stavudine: peripheral neuropathy

Lamivudine: LEAST toxic

Nonnucleoside reverse transcriptase inhibitors

MOA: don't require metabolic activation and inhibit reverse transcriptase at a different site than NRTI's

Drugs: delavirdine, nevirapine, efavirenz, & adefovir

SE: NOT myelosuppressant 

Protease Inhibitors

MOA: aspartate protease is a viral enzyme that cleaves polypeptides in HIV buds to form mature virus (PI's bind to a dipeptide inhibiting the enzyme)

Uses: most often used in combo w/ 2 NRTI's for HIV regimens

Indinavir: nephrolithiasis (renal stones) inhibition of P450 (3A4 isoform) very powerful

Ritonavir: (most often used) GI distress, asthenia, paresthesias, also inhibits P450

SE (both): disordered lipid and CHO metabolism (central adiposity and insulin resistance)

Fusion inhibitor

Enfuvirtide

MOA: binds gp41 and inhibits fusion of HIV-1 to CD4 cells (used in non-naive pts)

Amantidine

MOA: blocks attachment, penetration, and uncoating of influenza A virus (target is the M2 protein in the virus membrane)

Uses: prophylaxis mainly

SE: CNS effects, nervousness, insomnia, seizures, atropine-like peripheral effects and livedo reticularis

Zanamivir & Oseltamivir

MOA: inhibit neuraminidases of influenza A and B (enzymes that allow the clumping of virions so there a more particles for infecting host cells)

Uses: prophylaxis, but may decrease duration of flu 2-3 days

SE: N/V, zanamivir is inhalational so throat irritation

Ribavirin

MOA: triphosphate inhibits viral RNA polymerase and end-capping of viral RNA

Uses: manage RSV, some influenza A/B, lassa fever, hantavirus, adjunct in hep C

SE: hematotoxic, upper airway irritation, teratogenic