Anti Virals Flashcards
Acyclovir
Guanosine analog; viral DNA poly is 10-30x more sensitive to the drug than the host DNA poly. PO IV or topical, 15-30% bioavilability oral; renal elim. HSV 1 HSV2 and Varicella zoster
Valacylcovir
like acyclovir (ester producing pro drug converted to acyclovir) has increased oral bioavailability (54-70%) HSV 1 and 2 and Varicella Zoster
Ganciclovir and Valganciclovir
guanine analogs, initial phosphorylation by viral phosphotransferase UL97. Triphosphate derivative competes with d-GTP substrate to inhibit CMV DNA polymerase. Intracellular half live >24hrs. Ganciclovir IV dosing, valgan PO dosing
Treat - CMV HSV VSV HHV8 (Kaposi Sarcoma)
Cidofovir
host kinases convert to disphosphate from monophos nucelotide analogue that is active moiety; inhibits viral DNA polymerase. IV eliminated by kidney including tubular secretion. Broad CMV, other herpese HHV6 HHV8 adenovirus, vaccinia (pox) polyoma, papilloma. Nephrotoxic, give with probenecid and saline prehydration to reduce toxicity. Ganciclovir resistant strains are usually susceptible to Cidofovir
Foscarnet
inorganic pyrophosphate analog that inhibits viral DNA polymerase and reverse transcriptase; does not require phosphorylation. IV only. entrs macrophages. Herpes including CMV HHV6 HHV8 HIV. Nephrotoxic, prehydrate with saline
Maraviroc: entry inhibitor
Entry Inhibitor: Anti retro viral. Block HIV-1 into cells, co receptor antagonist. No cross resistant with other drug classes, CYP3A4 substrate subject to drug interactions
Enfuvirtide: fusion inhibitor
Fusion inhibitor - synthetic 36 amino acid peptide bibds gp 41 subunit of HIV-1 envelope glycoprotein. Prevents conformational changes required for fusion of viral and ceullar membranes. Only HIV drug given by parenteral injection (sc). proteolytic elimin. no drug interactions
Nucleoside RTI Abacavir Didanosine Emtricitabine Lamivudine (also HBV) tenovir disoproxil (also HBV) Zidovuvine
Prodrug needs to be phosphorylated, intracellular half life longer than serum, toxicity include mitochondrial toxicity, didanosine has dose dep pancreatitis, most active against HIV 1 and 3
Non Nucleoside RTI Efavirenz Etravirine Nevirapine
dissimilar in structure but exert antiretroviral activity by the same allosteric mechanism of action; work against HIV strains with reduced susceptibility to nuceloside RTI, only active against HIV 1, rapid resistance develops against all members of this class if employed incompletely suppressive regimens. more GI intolerance and skin rash than Nucleotid RTI
Integrase inhibitor - Dolutegravir Elvitegravir Rltegravir
targets integrase mediating the strand transfer step of HIV 1 and 2 integration wtih the host cell DNA by preventing formation of covalent bonds btw viral DNA and host DNA. Hepatic metaboism by phase 1 CYP3A and phase 2 conjugation rxns. well tolerated
Protease Inhibitors: Atazanavir, Ritonavir, Darunavir
structure based on specific amino acid dequences recognized and cleaved in HIV proteins, late step in development of HIV. Drugs block post translational processing of GAG POL polyprotein precursor that participates in viral budding. Active against HIV1 and 2
Entecavir Adefovir disoproxil
target HBV dna poly for Hep B and C
Ledipasvir-sofosbuvir (Harvoni)
chronic hepatitis C genoytpe 1, potent inhibitor of HCV Ns5A; sofosbuvir is a nucleotide analog inhibitor of HCV Ns5B polymerase key enxyme mediating HCV RNA replication. Triphosphate form is incorporated into by elongating RNA primer starand resulting in chain terminiation
Glecaprevir and Pibrentasvir (MAvyret)
combo therapy for all 6 genotypes of HCV. 98% cure rate with 8 week regimen. Gleca inhibits HCV rpotease NS3/4A NS5A Pibrentasvir inhibits HCV Ns5A
Interferon Alfa
alfa 2a and 2b used for HBV and HCV inhibit viral protein synthesis; use for chronic hep B chronic Hep C, low response rates and high cost limit use
