Antiviral Drugs Flashcards
Acyclovir
Action: Guanosine analog; preferentially inhibits viral DNA polymerase by chain termination; monophosphorylated by HSV/VZV thymidine kinase and not phosphorylated in uninfected cells.
Uses: HSV and VZV; weak activity against EBV; no activity against CMV.
Toxicity: Obstructive crystalline nephropathy; acute renal failure if not adequately hydrated.
Resistance: Mutated viral thymidine kinase.
Other drugs in class: Famciclovir; valacyclovir (better oral bioavailability).
Ganciclovir
Action: Guanosine analog; preferentially inhibits viral DNA polymerase; monophosphorylated by CMV viral kinase.
Uses: CMV (especially in immunocompromised patients).
Toxicity: Leukopenia; neutropenia; thrombocytopenia; renal toxicity; more toxic than acyclovir.
Resistance: Mutated CMV DNA polymerase; lack of viral kinase.
Other drugs in class: Valganciclovir (better oral bioavailability).
Foscarnet
Action: Viral DNA polymerase inhibitor; does not require activation by viral kinase.
Uses: CMV retinitis in immunocompromised patients when ganciclovir fails; acyclovir-resistant HSV.
Toxicity: Nephrotoxicity.
Resistance: Mutated DNA polymerase.
Oseltamivir
Action: Inhibits influenza neuraminidase = decreased release of progeny virus.
Uses: Treatment and prevention of both influenza A and B.
Other drugs in class: Zanamivir.
Ribavirin
Action: Inhibits synthesis of guanine nucleotides by competitively inhibiting inosine monophosphate dehydrogenase.
Uses: RSV; chronic hepatitis C.
Toxicity: Hemolytic anemia; severe teratogen.
Sofosbuvir (Sovaldi)
Action: Inhibits Hepatitis C RNA polymerase.
Telapravir (Incivek)
Action: Inhibits Hepatitis C protease.
Interferon (IFN)
Action: Glycoproteins normally synthesized by virus-infected cells; exhibiting a wide range of antiviral and antitumoral properties; regulates the Jak/STAT pathway.
Uses: IFN-α (chronic hepatitis B and C, Kaposi sarcoma, hairy cell leukemia, condyloma acuminatum, renal cell carcinoma, malignant melanoma); IFN-β (multiple sclerosis); IFN-γ (chronic granulomatous disease).
Toxicity: Bone marrow suppression (neutropenia); myopathy.
Efavirenz
Action: Non-nucleotide reverse transcriptase inhibitor (NNRTI); bind to reverse transcriptase at site different from NRTIs.
Uses: HIV.
Toxicity: CNS toxicity; skin rashes; hepatotoxicity.
Other: Do not require phosphorylation to be active or compete with nucleotides.
Other drugs in class: Nevirapine; delavirdine.
Lamivudine (3TC)
Action: Nucleotide reverse transcriptase inhibitor (NRTI); competitively inhibit nucleotide binding to reverse transcriptase and terminate the DNA chain (lack a 3′ OH group).
Uses: HIV.
Toxicity: Bone marrow suppression; peripheral neuropathy; lactic acidosis (nucleosides); rash (non-nucleosides); anemia (ZDV); pancreatitis (didanosine).
Other: Tenofovir is a nucleotide; the others are nucleosides and need to be phosphorylated to be active.
Other drugs in class: Abacavir (ABC); didanosine (ddI); emtricitabine (FTC); stavudine (d4T); tenofovir (TDF); zidovudine (ZDV, formerly AZT).
Enfuvirtide
Action: Fusion inhibitor; binds gp41, inhibiting viral entry.
Uses: HIV.
Toxicity: Skin reactions as injection site.
Other drugs in class: Maraviroc (binds CCR5 on surface of T cells/monocytes, inhibiting interaction with gp120).
Fosamprenavir
Action: Protease inhibitor; prevents cleavage of polypeptide by HIV protease (pol gene).
Uses: HIV.
Toxicity: Hyperglycemia; GI intolerance (nausea, diarrhea); lipodystrophy; ritonavir induces cytochrome P-450.
Other: Proteases end in -navir.
Other drugs in class: Atazanavir; darunavir; fosamprenavir; indinavir; lopinavir; ritonavir; saquinavir.
Raltegravir
Action: Integrase inhibitor; inhibits HIV genome integration into host cell chromosome.
Uses: HIV.
Toxicity: Hypercholesterolemia.
