Antiviral Agents Flashcards
Neuroaminidases (Oseltamivir, Zanamivir, Peramivir)
Mechanism: Inhibits NA that cleaves N-acetyl neuraminic acid. W/o this enzyme, virus aggregates @ cell surface,decreasing intracellular viral translocation and viral budding, resulting in decreased viral infectivity.
Pharmacokinetics:
O-oral/ prodrug. Renal excretion
Z-inhalation. Renal elim.
P-single IV dose.
Adverse:
O-nausea+vomit
Z-bronchospasm(COPD/asthma)
P - diarrhea and GI. Neutropenia.
Role: If started within 48 hrs -> may decrease severity and duration of symptoms. Prophylactic.
Used for both A and B influenza.
Inhibition of uncoating (amantidine, rimantidine)
Mechanism: blocks virally encoded H+ ion channel (M2 protein) preventing changes in intracellular pH necessary for uncoating.
Pharmacokinetics:
A- orally w/ accumulation in lungs. Excreted in urine -> requires dosage adjustment.
R- hepatic elimination. Excreted in breast milk.
Adverse:
A - CNS symptoms (insomnia, concentration difficulty, etc)
R - poor CNS penetration so better tolerated. Teratogenic in animals, not recommended for pregnancy.
Uses: For prophylaxis and treatment of influenza A infections (B doesn’t have M2 target)
Can be given w/ vaccine for vulnerable pts.
If given 1-2 days prior to and 6-7 days during infection, will reduce incidence and severity of symptoms.
Inhibitors of Viral Genome Replication - Viral DNA polymerase (acyclovir, valacyclovir, penciclovir, famciclovir)
Mechanism: converted to active triphosphate by intracellular kinases but initial phosphorilation mediated by VIRAL thymidine kinases. Active form competes actively w/ dGTP for viral DNA polymerase, which is included as nucleic acid analog in replicating viral strands. Terminates DNA replication and strand elongation.
Pharmacokinetics:
A - IV and topical, poor oral
V - prodrug of A, given orally v good
P- acyclic guanosine analog, topical only
F - penciclovir prodrug, increases oral availability.
Renally excreted -> dosage adjustment. Neonatal clearence only 1/3 of adults.
Toxicities: minor, headache, nausea, renal dysfunction
IV acyclovir - encephalopathy
Use: Oral acyclovir shortens symptoms during primary and reoccurring genital herpes and reduces duration of pain (not time of healing) in recurrent herpes labialis.
IV acyclovir - treatment of CHOICE for herpes simplex encephalitis, neonatal HSV
Topical vidarabine and trifluridine -> HSV kerataconjunctivitis and reoccurent epithelial keratitis.
Varicella Zoster Virus – oral acyclovir decreases number of lesions and during of chicken pox and shingles, but need high doses and shit.
Docosanol – topical treatment begun within 12 hrs of symptoms or lesion onset reduces healing time.
Ribavirin (nucleoside analog, treatment of RSV)
Mechanism: converted to ribavirin-TP by cellular kinases. Inhibits GTP-dependent 5’ capping of viral mRNA, decreases their stability and translatability.
Pharmacokinetics - Oral bioavailability (45-65%) increases w/ fatty meals. Elimination via hepatic metabolism and renal excretion.
Adverse: Inhalation - well tolerated, irritation. Oral - systemic hemolytic anemia, teratogenic, don’t administer during pregnancy.
Use: Respiratory Syncitial Virus - and pneumonia only for severely immunocompromised pts.
Hep C - oral ribavirin combined w/ interferon formerly the standard of chronic HCV infection
Inhibitors of Viral DNA polymerase -> Ganciclovir, Valganciclovir
Metabolism: Cellular uptake and initial phosphorylation is mediated by viral protein kinase UL97 in CMV (viral vs host selectivity)
Ganciclovir-TP competes w/ cellular dGTP for viral DNA polymerase, which then incorporates into replicating viral DNA strand, which ceases further DNA chain elongation
Pharmacokinetics: Ganciclovir has poor oral bioavailability but good distribution into bodily fluids administered IV.
Valg. is prodrug -> converted into ganci by GI and hepatic esterases
Toxicity: Less selective toxicity than acyclovir -> myelosuppression w/ neutropenia and thrombocytopenia is major side effect.
Use: Treatment and chronic suppression of CMV retinitis in immuno-compromised people as well as transplant pts. Opthalmic gel effective in treating HSV keratitis.
Foscarnet
Mechanism: inorganic pyrophosphate analog, unique -> not NOT REQUIRE CELLULAR ACTIVATION. Noncompeteitively binds to pyrophosphate binding side of RNA and DNA polymerases. Blocks viral replication.
Pharm: IV -> unchanged in urine.
Toxicity: nephrotoxicity and hypocalcemia, sometimes CNS abnormalities
Use: effective against CMV retinitis. Effective against ganciclovir resistant CMV infections and acyclovir resitant HSV.
