Anti-virals Flashcards
ADME of acyclovir
Administered topically and IV.
*IV can cause nephrotoxicity, hepatotoxicity
Clinical use of acyclovir
HSV infections- herpes encephalitis, neonatal HSV, severe HSV/VSV infections (can penetrate CSF).
*Give foscarnet if resistant to acyclovir (would occur from mutation to viral thymidine kinase)
Mechanism of action of ganciclovir
An acyclic guanosine analog (requires 3x phosphorylation like acyclovir) and first phosphorylation done by CMV kinase
- tx and prophylaxis post-transplant for CMV
- can cause myelosuppression
Mechanism of action of foscarnet
Treats acyclovir-resistant strains via IV only (doesn’t require activation by the virus). Inhibits DNA and RNA polymerase, HIV RT
- renal toxicity
- hyperphosphatemia, hypokalemia/calcemia/magnesemia
Mechanism of action of anti-influenza drugs (oseltamivir, zanamivir)
Neuraminidase inhibitors (inhibit release of influenza progeny by competing for enzyme). Must be given within 48 hours of onset of symptoms. Fights influenza A and B. Zanamivir works against oseltamivir-resistant strains.
Mechanism of action of ribavirin (anti-hepatitis drug)
Guanosine analog phosphorylated by host cell –> blocks capping of viral mRNA and inhibits viral RNA-dependent polymerase (causes RNA mutations). May be given with interferon
*can cause hemolytic anemia
Mechanism of action of interferons (anti-hepatitis)
Exert antiviral, immunomodulatory, and antiproliferative actions. Boost the immune system (increase phagocytic activity, cytotoxic T cells, etc). Induce intracellular signals that inhibit viral development and release.
Contraindications and toxicities of interferons
C: pregnancy (abortifacient)
T: flu-like symptoms (very bad)
Mechanism of action of Simeprevir (anti-hepatitis)
Protease inhibitor (NS3/4A). *can lead to drug-drug interactions b/c P450 inhibitor and P-glycoprotein transporter
Mechanism of action of sofosbuvir and ledipasvir (anti-hepatitis)
NSB5 RNA polymerase inhibitor that works against all HCV genotypes (1-6) and protease-resistant strains.
Sofosbuvir is a component in…
Harvoni (combined with Ledipasvir)
Sofosbuvir toxicity
Sofosbuvir is a p-glycoprotein transporter and shouldn’t be used with p-gp inducers like rifampin
Name the nucleoside reverse transcriptase inhibitors (NRTIs)
Abacavir, lamivudine/emtricitabine, tenofovir
Mechanism of action of NRTIs
Activated by phosphorylation to triphosphate, competitively inhibit reverse transcriptase
General toxicities of NRTIs
Can cause lactic acidosis w/ hepatic steatosis from inhibiting mitochondrial fxn and causing buildup of triglycerides
Unique toxicities of abacavir
Remember, an NRTI. Can cause MI (caution with CV dz), fatal hypersensitivity rxns (NEVER give to HLAB5701 mutation
Lamivudine/Emtricitabine usage
(NRTI) Used for HBV also by inhibiting HBV RT. Always given with tenofovir.
Mechanism of action of tenofovir
A nucleotide RT inhibitor (NtRTI) that causes chain termination after incorporation into viral DNA. Given with emtricitabine for first-line therapy.
*Can cause tubular necrosis, renal failure, Fanconi’s syndrome
Name the non-nucleoside reverse transcriptase inhibitors (NNRTIs)
Efavirenz
Mechanism of action of efavirenz
(NNRTI) Allosteric inhibitor- binds directly to HIV-1 RT inhibiting DNA and RNA-dependent DNA polymerase activity. Denatures the RT once bound.
- Significant P450 inducer
- Can cause psych disturbances/nightmares
Mechanism of action of protease inhibitors
Mimics peptide bonds (peptidomimetics) to trick the protease, inhibiting it and preventing release of core proteins for viral maturation
Name the protease inhibitors
Ritonavir, atazanavir, darunavir, lopinavir (only w/ ritonavir combo)
Unique characteristics of ritonavir
CYP3A4 inhibitor, so it’s given w/ other PIs to increase serum levels (booster)
- increases triglycerides/LDL –> fat pad (lipodystrophy)
- elevated aminotransferases
Contraindication of darunavir
Sulfa allergy
