Question
Acyclovir
Answer
Acyclovir is a guanosine analogue antiviral, the prototype anti-herpes agent.
MOA: acyclovir → monophosphorylated by virus-encoded thymidine kinase (present in HSV/VZV-infected cells, not uninfected cells — the first selectivity step) → further phosphorylated by host kinases to the active triphosphate → incorporated into viral DNA by viral DNA polymerase → chain termination (lacks the 3’-hydroxyl group needed for the next nucleotide). Viral DNA polymerase also binds acyclovir triphosphate with much higher affinity than host polymerase — a third, independent layer of selectivity.
Uses: herpes simplex virus infections (genital, orolabial, encephalitis), varicella-zoster virus infections (chickenpox, shingles) — most effective when started early.
Adverse effects: generally well tolerated given its triple selective-toxicity mechanism; crystalline nephropathy with rapid IV infusion/inadequate hydration, GI upset, and reversible neurotoxicity (confusion, tremor) at high doses, particularly in renal impairment.