- 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

Polyenes specifically target fungal membranes. They bind ergosterol, which is the principal sterol in fungal membranes as opposed to cholesterol found in host membranes. This interference creates a transmembrane channel and the resultant change in permeability allows leakage of intracellular components

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

only administered IV

Widely distributed

Poor tissue penetration. Negligable CSF or urine penetration.

Highly protein bound

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

Metabolised by the liver

actively excreted in the kidneys unchanged (blocked by probenecid)

poorly characterized but does not accumulate in renal failure

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

Dose related nephrotoxicity
Infusion related reactions (hypotension, fever, rigors)

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

Broad antifungal cover including candida, Cryptococcus, aspergillus and zygomyces

Antiviral

Antifungal

Synthetic nucleoside analogue

Polyene

Level 3

Level 3