Antivirals

Question 1

Amantadine

Answer 1

• mechanism: Block M2 proton ion channel and prevent “uncoating” of viral RNA
• kinetics: requires renal dosing
• clinical: Prophylaxis for influenza type A; reduce symptoms if given w/in 48 hours
• toxicity/interactions: GI irritation, dizziness, ataxia, slurred speech

Question 2

Rimantadine

Answer 2

• mechanism: Alpha-methyl derivative of amantadine; blocks M2 proton ion channel and prevents “uncoating” of viral RNA
• kinetics: Longer half-life than amantadine; requires no renal dosing
• clinical: Prophylaxis for influenza type A; reduce symptoms if given w/in 48 hours
• toxicity/interactions: GI irritation, dizziness, ataxia, slurred speech

Question 3

Acyclovir

Answer 3

• mechanism: Guanosine analogue – activated (using thymidine kinase) to form acyclovir triphosphate, which interferes with viral synthesis, by 1) acts as a competitive substrate for DNA polymerase, and 2) leads to chain termination after its incorporation into viral DNA
• kinetics: Topical, oral, parenteral; short half-life (requires many dosages/day when used orally); renal excretion (requires renal dosing)
• clinical: Treatment and Prophylaxis for: Herpes-Simplex Virus (HSV1, HSV2); Varicella zoster virus (VZV)
• toxicity/interactions: Oral - GI distress, headache; IV- delirium, tremor, seizures, hypotension, nephrotoxicity
• misc: TK (-) resistant strains

Question 4

Valcyclovir

Answer 4

• mechanism: Prodrug converted to acyclovir by hepatic metabolism
• kinetics: Longer duration than acyclovir
• clinical: Treatment of HSV and VZV
• toxicity/interactions: Nausea, headache, vomiting, rarely rash
• misc: Reaches plasma levels 3-5x that of acyclovir and longer duration of action than acyclovir

Question 5

Famciclovir

Answer 5

• mechanism: Prodrug - converted to penciclovir by hepatic metabolism
• kinetics: Similar to acyclovir - short half-life and renal excretion
• clinical: HSV and VZV
• toxicity/interactions: Headache, nausea, diarrhea
• misc: TK(-) resistant strains

Question 6

Penciclovir

Answer 6

• mechanism: Guanosine analogue - activated by thymidine kinase – inhibits DNA polymerase (but does not cause chain termination)
• kinetics: topical
• clinical: Herpes Simplex Virus
• toxicity/interactions: Rarely rash at site of application

Question 7

Ganciclovir

Answer 7

• mechanism: Guanine derivative - triphosphorylated to form a nucleotide – inhibits DNA polymerase and causes chain termination
• kinetics: IV; penetrate CSF and eye
• clinical: Treatment and prophylaxis for: cytomegalovirus (CMV); also active against HSV
• toxicity/interactions: Leukopenia, thrombocytopenia, mucositis, hepatic dysfunction, seizures; causes neutropenia when used w/ zidovudine or myelosuppressing drugs
• misc: Intraocular implant form for CMV retinitis

Question 8

Foscamet

Answer 8

• mechanism: Phosphonoformate derivative - inhibits viral RNA polymerase, DNA polymerase, and HIV reverse transcriptase
• kinetics: IV; Penetrates CSF
• clinical: Tx and prophylaxis: CMV; used against ganciclovir-resistant CMV and acyclovir-resistant HSV
• toxicity/interactions: Nephrotoxicity; electrolyte imbalances (hypocalcemia), genitourinary ulceration, CNS effects (headache, hallucinations, seizure)
• misc: Use when acylovir and ganciclovir don’t work and in immunosuppressed

Question 9

Sorivudine

Answer 9

• mechanism: Thymine analogue – activated via triphosphorylation - inhibits DNA synthesis
• clinical: HSV, VZV, Epstein Barr Virus
• toxicity/interactions: Dangerous interaction w/ flucosytine
• misc: Not FDA approved

Question 10

Idoxuridine

Answer 10

• mechanism: Nucleoside analogue (deoxyuridine) - incorporated by DNA polymerase and iodine side chain prevents base pairing
• kinetics: topical only
• clinical: HSV keratitis
• toxicity/interactions: Irritation, blurred vision, photophobia

Question 11

Vidarabine

Answer 11

• mechanism: Adenine analogue - activated via triphosphorylation and inhibits DNA synthesis
• kinetics: Rapid metabolic inactivation
• clinical: CMV, HSV, VZV - for systemic infections; topical - for herpes keratitis
• toxicity/interactions: GI irritation, parasthesias, tremor, convulsions, hepatic dysfunction

Question 12

Trifluridine

Answer 12

• mechanism: Fluorinated pyrimidine nucleoside that inhibits viral DNA synthesis by competing with thymidine triphosphate for incorporation by the viral DNA polymerase
• kinetics: topical only
• clinical: HSV1/2 epithelial keratitis
• toxicity/interactions: Mechanism unknown; inhibits the replication of a wide range of DNA and RNA viruses – inhibits guanosine triphosphate formation, prevents capping of viral mRNA, and can block RNA-dependent RNA polymerases

Question 13

Ribavarine

Answer 13

• mechanism: Mechanism unknown; inhibits the replication of a wide range of DNA and RNA viruses – inhibits guanosine triphosphate formation, prevents capping of viral mRNA, and can block RNA-dependent RNA polymerases
• kinetics: Oral, IV, aerosole; kidney excretion (requires kidney dosing)
• clinical: DNA and RNA viruses- influenza A and B, parainfluenza, respiratory syncytial virus (RSV), paramyxoviruses, HCV, HIV
• toxicity/interactions: Teratogen; dose-dependent hemolytic anemia; aerosol form – bronchial irritation
• misc: Use w/ IFN-alpha for chronic HCV