Antiviral agents Flashcards
Primary means to control viral spread
public health measures and prophylactic vaccines
Steps of Influenza entry
- Binds cell surface of airway epithelial cell and is endocytosed
- Acidic environment causes hemagglutin change that causes fusion w/ endosomal membrane
- Activation of proton influx through viral M2 proton channel elicits release of RNA genome
- Egress- hemagglutin interacts with cellular sialic acid moieties, neuroaminidases cleave the sialic acid moieties
3 drugs that inhibit viral neuraminidase
- oseltamivir
- zanamivir
- peramivir
Route: oseltamivir
orally as prodrug
Route: Zanamivir
Inhalation
Route: Peramivir
Single IV dose
Use of oseltamavir, zanamivir, peramivir in Influenza
- within 48 hours- decrease severity in A or B
- prophylactic in high risk
Antivirals that clock virally-encoded H ion channel (M2 protein) (2)
- Amantadine
2. Rimatadine
Amantadine excretion
- unchanged in urine requiring dosage adjustment if impaired renal functino
Rimantidine elimination
hepatic with t1/2 12 hours
Amantadine and rimantidine use in influenza
- prophylaxis and treatment of influenza A
- 1-2 days prior and 6-7 days during infection
- if 48 hours after- only slight therapeutic
Amantadine adverse reaction
insomnia, concentration difficulty, lightheadedness, headache
Rimantadine adverse side effects
better tolerated due to poor CNS penetration
Highest defgree of selective toxicity in nucleoside analogs
activated by viral kinases rather than host cell kinases
Antiherpes drugs (4)
- Acyclovir
- Valacyclovir
- Penciclovir
- Famciclovir
Mech of acyclovir
- viral thymidine kinase phosphorylates acyclovir, other enzyme take to triphosphate form
- acyclovir-TP terminates further DNA replication and strand elongation
- DNA containing acyclovir_TP (competes with GTP) irreversibly binds and inactivates viral DNA polymerase
Most common resistance to acyclovir
reduced or loss of expression of viral thymidine kinase
Pharmicokinetics: acyclovir
Oral absorption poor (15-30%); not affected by food. Also available in topical and
intravenous formulations
Pharmacokinetics: Calacyclovir
yl ester prodrug of acyclovir; given orally achieves plasma levels 3-5 times
higher than acyclovir (equivalent to IV administration)
Pharmacokinetics: Penciclovir
Acyclic guanosine analog; poor oral absorption, topical only (more effective than
topical acyclovir)
Pharmacokinetics: famciclovir
Penciclovir prodrug that increases oral bioavailability to 70%
Elimination: Acyclovir
Acyclovir is renally excreted (adjust dosage if renal impairment). Neonatal (
Dosing: HSV vs. VZV
oral acyclovir higher for VZV
Inhibitor of viral penetration
Docosanol
Drug for RSV
Ribavirin- purine nucleoside analog
Adverse reactions of Ribavirin
- conjunctival or bronchial irritation
2. hemolytic anemia
3. teratogenic
ONLY use in immunocompromised patients
RSV immunoprophylaxis
palivizumab
Antivirals for CMV infections
- Ganciclovir (intraocular) and valganciclovir (oral)
2. Foscarnet
Mechanism of action: ganciclovir and valganciclovir
- initial phosphorylation by viral protein kinase UL97
Resistance to ganciclovir and valganciclovir
mutation in UL97
mutation in viral DNA pol (UL54)
Adverse reactions of ganciclovir and valganciclovir
- less selective toxicity because host kinase can perform first phosphorylation step
- GI
Foscarnet
- inorganic pyrophosphate analog
- does not require cellular activation
- noncompetitively binds to pyrophosphate binding site of RNA and DNA polymerases
- used when mutation in UL97
Adverse reaction od foscarnet
- nephrotoxicity and hypocalcemia
- CNS abnormalities
