Drug card 5: anti viral Flashcards
Zanamivir, oseltamivir
Inhibits influenza NA, decreases the release of progeny virus
Clinical Treat and prevent influenza A and B
Ribavirin
Inhibit synthesis of guanine nucleotide by competitively inhibiting IMP dehydrogenase
Clinical: RSV, chronic hepatitis
Toxicity: HEMOLYTIC ANEMIA, SEVERE TERATOGEN
Acyclovir
Monophosphorylated HSV/VZV thymidine kinase.
Guanosin analog. Triphosphate formed by cellular enzymes.
Preferentialy inhibit viral DNA polymerase inhibitor
Clinical: HSV, VZV but little EBV, and no against CMV.
Valacyclovir: a prodrug of acyclovir, has better oral bioavailability.
For herpes zooster, use a related agent, famciclovir
Toxicity: few serious adverse effects
Resistance: mutated viral thymidine kinase.
Ganciclovir
5’ monophosphoate formed by a CMV viral kinase, Guanosine analog. Triphopshate formed by cellular kinase. Preferentially inhibit viral DNA pol
Clinic: CMV
Valganciclovir: produg of ganciclovir, has better oral availability.
Toxicity: LEUKOPENIA, neutropenia, throbocytopenia, RENAL toxicity, more toxic to host enzymes than acyclovir.
Resistance: mutated CMV pol or lack of viral kinase.
Foscarnet
Viral DNA pol inhibitor that binds to pyrophosphate-binding site of the enzyme
DOES NOT require activation by viral kinase
Clinical: CMV retinitis when ganciclovir famils, or acyclovir resistant HSV.
Toxicity: RENAL toxicity as well
Resistance: mutated DNA pol
Cidofovor
Preferentially inhibit viral DNA pol
DOES NOT require phosphorylation by viral kinase
Clinical: CMV retinitis, acyclovir-resistant HSV, long half life
Toxicity: nephrotoxicity (co administer with probenecid and IV saline to reduced toxicity)
HIV therapy
Initiate HAART when patients present with AIDS defining illnss, low CD4 cell counts (<500) or high viral loads. Regimen consists of 3 drugs to prevent resistance
2 nucleoside RT inhibitor +
1 non nucleoside RT
OR 1 protease inhibitor
OR 1 integrase inhibitor
Protease drugs
Blocks pol gene whcih cleaves polypeptide, preventing maturation of new viruses.
Ritonavir can boos other drug concentrations by inhibiting p450.
All proteases end in navir “never tease a protease”
Toxicity: HYPERglycemia, GI intolerance (diarrhea, nausea), lipid dystrophy, nephrotoxicity, hematuria (indinavir)
NRTIs
Tenofovir does NOT need to be activated; others have to be phosphorylated to be active.
ZDV is used for general prophylaxis and during pregnancy to reduce transmission
Tenofovir, emtiricitabine, abacavir, laminduvine, zidovuvine (ZDV, formally AZT)l, didanosine, stavudine
“Have you dined (vudine) with my nuclear family?”
Toxicity: bone marrow suppression (can be reversed with GCSF and EPO), peripheral neuropathy, lactic acidosis, rashy (non nucleoside) anemia (ZDV)
NNRTi
Nevirapine, efavirenz, delavirdine
Binds to RT at site different from NRTIs
Does not require pohspohrylation
Toxicity: same as NRTI
Integrase inhibitor
Raltegravir
Toxicity: hypercholesterolemia
Inteferons
Clinical:
Alpha: chronic hepatitis B and C, Kaposi’s sarcoma
Beta: MS
Gamma: CGD
Toxicity: neutropenia, myopathy
