Flashcards in Antiviral therapy Deck (14):
Inhibit influenza neuraminidase -> decrease release of progeny virus
treat and prevent both Influenza A and B
Acyclovir, famciclovir, valacyclovir
Guanosine analogs. Phosphorylated by HSV/VZV THYMIDINE kinase and not phosphorylated in uninfected cells
inhibits viral DNA polymerase
HSV and VZV. Weak against EBV and no activity against CMV
HSV - mucocutaneous and genital lesions and encephalitis
Prophylaxis in Immunocompetents. No effect on latent infections.
Valacyclovir - prodrug for acyclovir. better oral availability
Tox: crystalline nephropathy and acute renal failure
MOR: mutated viral thymidine kinase
5-monophosphate by CMV viral kinase. Guanosine analog. Triphosphate by cellullar kinase.
inhibits viral DNA polymerase.
Use: CMV esp in immunocompromised.
Tox: Leukopenia, neutropenia, thrombocytopenia, renal toxicity
MOR: mutated viral kinase
Viral DNA/RNA polymerase inhibitor and HIV reverse transcriptase inhbitor. Does not need activation by viral kinase
Use: CMV retinitis in immunocompromised patients when gangciclovir fails; acyclovir resistant HSV
Tox: nephrotoxicity, electrolyte prob: hypo/hypercalcemia, phosphatemia, hypokalemia, hypomagnesemia); Seizures!
MOR: mutated DNA polymerase
inhibits viral DNA polymerase. No need phosphorylation by viral kinase
Use: CMV retinitis in compromised. Acycovir resistant HSV.
Tox: nephrotoxicity; give probenicid to decrease toxicity
HAART - at time of HIV diagnosis; strong indication: low CD4 cell counts
Abacavir, Didanosine, lamivudine, Stavudine, Tenofovir, Zidovudine ( for general prophylaxis and pregnancy to decrease fetal transmission)
Competitively inhibit nucelotide binding to reverse transcriptase and terminate DNA chain (lacks 3' OH group)
Tenofovir is Nucleotide; the others are nucleosides, so need phosphorylation
Tox: Bone marrow suppression (reverse with G-CSF and eryhtropoietin), peripheral neuropathy, lactic acidosis, anemia (ZDV), pancreatitis (didanosine)
Delavirdine, Efavirenz, Nevirapine
Bind reverse transcriptase at a different site than NRTI. Dont need phosphorylation to be active or compete with nucleotides
Toxicity: Rash and hepatotoxicty - all NNRTI
Vivid dreams and CNS symptoms - efavirenz
Delavirdine and efavirenz are containdicated in pregnancy
Assembly of virions depend on HIV-1 protease (pol gne) - cleaves polypeptides of HIV mRNA. Protease inhibitors prevent maturation of new viruses
Ritonavir increase other drug concentration by inhibiting cyt P450.
Tox: Hyperglycemia, GI intolerance, lipodystrophy, nephropathy, hematuria.
**Rifampin - CYP induces is CI with protease inhibitos b/c can decrease protease inhibitor concentration**
Inhibits HIV genome integration into host cell chromosome by reversibly inhibiting HIV integrase
Increase creatine kinase - toxicity
Enfuvirtide: binds gp41, inhibiting viral entry
maraviroc: Binds CCR5 on Tcell or monocyte surface and inhibits interaction with gp120
Tox: skinreaction at injection sites
Glycoprotein made by virus infected cells, antiviral and antitumor properties
IFN-alpha: Chronic hepatitis B and C, Kaposi sarcoma, hairy cell leukemia, condyloma acuminatum, RCC, malignant melanoma
IFN-Beta: Multiple sclerosis
Toxicity: Neutropenia, myopathy
Hepatitis C therapy
Ribavirin, SImeprevir(protease inhibito, prevent viral replication), Sofosbuvir (inhibit HCV RNA dep-RNA polymerase - chain terminator)
Ribavirin: Inhibit guanine nucleotides by competitively inhibiting inosine monophosphate dehydrogenase
Use: Chronic HCV, also used in RSV (pavlizumab in children)
Sofosbuvir, Simeprevir - not monotherapy; used with Ribavirin
Toxicity: hemolytic anemia, severe teratogen