Core pharmacology

Class Group

Antiviral

Legacy Cicm Level

Level 3

Introduction

Synthetic nucleoside analogue

Mechanism of action

- Inhibits nucleic acid synthesis
- Cells infected with HSV or VZV contain virally encoded thymidine kinase that converts acyclovir to acyclovir monophosphate. This is then converted to an active triphosphate that inhibits viral DNA polymerase and acts as a chain terminator
- Thymidine kinase in non-infected cells has a low affinity for acyclovir
- Whilst useful for HSV and VZV, it does not eradicate them and is only useful if given at the start of an infection

Antimicrobial Spectrum

Herpes Simplex (1 and 2) and Varicella Zoster.
Lacks CMV cover

Adverse Effects Toxicity

Renal
- Rapid IV administration may precipitate renal failure
Thrombophlebitis
- Highly irritating to veins and extravasation may lead to ulcers
CNS
- Tremors, confusion, seizures and coma in rapid infusion

Absorption

Erratic intestinal absorption and low bioavailability (25%). Oral valine-esterified prodrug valacyclovir improves absorption

Distribution

Widely distributed

Metabolism

Oral valine-esterified prodrug valacyclovir is rapidly hydrolyzed in the blood

Excretion

actively excreted in the kidneys unchanged (blocked by probenecid)