Pharmacology Antivirals

• Active against: HSV-1, HSV-2, VZV, CMV and EBV
• Guanine nucleoside analog: (only difference is in deoxyribose moiety, cant get 5'3' synthesis, get chain termination)
• selective drug: accumulated only in infected cells
• affects synthesis of viral DNA
• Oral Bio; 15-20%
• T1/2: 2-3 hr
• cleared by glomerular filtration and tubular secretion
• Used for: genital herpes, herpes proctitis, varicella, zoster, herpes encephalitis severe herpes (IV), herpes labialis(topical)

Acyclovir --> monophosphate derivative --> di-triphosphate analogs--> blocks viral DNA polymerase

• Enzyme 1: viral thymidine kinase
• Enzyme 2: cellular kinase
• (mutation in either enzyme can cause resistance to acyclovir)

• Well tolerated in general
• Common: pain, swelling, reddness at place of injection
• Uncommon: stomach pain, diarrhea, renal insufficiency(crystalline nephropathy), headache
• Rare: coma, seizure, neutropenia, leukopenia, anorexia, fatigue, hepatitis

• Pro drug converted into acyclovir
• serum conc 3-5 times higher than acyclovir
• oral bio: 54% about 1/2 in CSF
• no other advantage over acyclovir, same mechanism, same side effects

• Prodrug converted to penciclovir
• guanosine analog
• Active against HSV1,2, VZV, EBV, and HBV
• Actived by viral TK (phosphorylation)
• Competitive inhibtion of DNA polymerase ONLY, no chain termination
• Has lower affinity for viral TK than acyclovir but achieves higher intracellular conc
• T1/2: 7-20 hr
• Well tolerated
• headache and gi intolerance uncommon

• active metabolite of famciclovir
• available for topical application against recurring herpes labialis

• Treats CMV and CMV retinitis
• Guanosine analog
• prodrug activated by viral PK phosphotransterase
• available in oral or IV forms
• T1/2: 2-4 hr
• resistance: mutation in drug target (phosphotransferase)
• Cross resistnace with strains resistant to acyclovir (TK deficiency)
• excreted by renal system

• Common: bone marrow suppression (neutropenia and thrombocytopenica occur in 20-40% and 5-20% respectively)
• Uncommon: renal insufficiency (crystallization of drug), fever, headache, pain at injection, tremor, tiredness, weakness
• Rare: skin rash and encephalopathy

• Ganciclovir prodrug
• hydrolyzed in intestine and liver
• 900mg qd
• plasma protein binding <2%
• renal ilimination
• Same ADR and MOA as ganciclovir

• Active against HSV, VZV,CMV, EBV, HHV-6, KSHV AND HIV-1.
• Also used for CMV retinitis (effective as ganciclovir)
• poor oral bio so IV only
• CSF is 1/2 of plasma
• T1/2: 3-7 h but 30% deposit in bond with T1/2 of months
• Nephrotoxicity (hypo or hyper phosphatemia, hypo magnesemia)
• N/v, anemia, high LFT
• CNS toxicity:headache, hallucinations, seizure

• cytosine analog
• active for: CMV retinitis and acyclovir resistant herpes, also HPV, poxvirus, adenovirus, and polyomavirus
• Cidofovir converts to cidofovir-diPO4
• Effective against TK strains cuz phosphrylation is independent of viral enzymes
• bindes to viral DNA polymerase and blocks DNA synthesis
• T1/2: cidofovir 2-6 h, dipo4 17-65h, cidofovir phosphocholine >87 h
• Nephrotoxic : give probenecid with it to protect kidney
• Uveitis, oxular hypotony, neutropenia, acidosis

• For Hep B
• potent NRTI
• lower dose that when used for HIV

• For Hep B
• NRTI
• failed for HIV
• nephrotoxic at higher doses

• For Hep B
• guanosine nucleoside analog
• Oral
• well tolerated
• side effects: HA, fatigue, dizziness, nausea

For Hep B

• For Hep C
• guanosine nucleoside analog
• oral used in combo therapy with IFN-a
• inhibits capping of viral mRNA but mech unknown
• teratogenic so contradicted to pregnant and anemic

subq or intramuscular

• sialic acid analog
• prodrug activated by esterases in GI or liver
• Selective inhibitor of influ A and B virus neuraminidases
• Prevents release of virus from infected cells (causes viral aggregation at the cell surface)
• resistance through mutations in neuraminidase and hemagglutinin
• oral bio: <5%
• renal excretion: 100%
• Inhaled or IV
• T1/2: 2.5-3 hr
• for treatment and prophylaxis

• Prodrug activated by esterases in gi and liver
• selective inhibitor of influ A and B virus neuraminidases
• Mech of Action and resistance same as Zanamivir
• Oral bio: 80%
• Effect of meal is negligible
• renal excretion 95%
• For treatment and prophylaxis
• ADR: mild Gi complain, HA

• Tricyclic amines
• target M2 protein with influ A
• inhibit uncoating of viral RNA
• oral bio: 90%
• rimantadine is 4-10x more active than amantadine
• Amantadine excreted unmetabolized in urine
• rimantadine undergoes extensive metabolism, reduce dose in renal or hepatic insufficiency
• Common side effects: GI (no appetite, nausea) and CNS(light headedness and insomnia)
• Cross resistance with each other
• decrease the symptoms of flu by 1-2 days, speed recovery and decrease the duration of virus shedding.