- 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

inhibit neurominidase resulting in impaired viral release from infected cells. Neurominidase cleaves the sialic acid on the cell membrane allowing viral budding.

Azoles disrupt ergosterol production by interacting with 14-alpha demthylase, a cytochrome P450 enzyme necessary to convert lanosterol to ergosterol. As ergosterol is an essential component of fungal cell membranes, inhibition of its synthesis leads to increased cell permeability causing leakage of contents.

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

Well absorbed orally (except miconazole)

only administered IV

Widely distributed

Fluc – good CSF penetration
Itra, Keto – no CSF penetration

Poor tissue penetration. Negligable CSF or urine penetration.

Itra, Keto – 99% PB

Highly protein bound

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

Fluc not metabolized well
Itra, Keto – metabolized by liver

Metabolised by the liver

actively excreted in the kidneys unchanged (blocked by probenecid)

Fluc – Urine unchanged
Itra, Keto – Excreted bile

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

1. Psychiatric symptoms
2. N/V/D
3. Bronchospasm

Fluc: N/V/D, Abdominal pain
Headache
Skin rash
Reversible alopecia
Rare: Hepatic failure, SJS
Should be avoided in Pregnancy
Drug interactions: (inhibitor of CYP3A4, CYP2C9)

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

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

Fluc: Candida
Cryptococcus
Coccidia
(No activity against histoplasma, blasto, sporotrichosis, Aspergillus, mucormycosis)

Broad antifungal cover including candida, Cryptococcus, aspergillus and zygomyces

Antiviral

Antiviral

Antifungal

Antifungal

Antiviral

Synthetic nucleoside analogue

Oseltamivir and Zanamivir

Triazoles: Fluconazole, Itraconazole, Voriconazole, Posaconazole
Imidazoles: Clotrimazole, Ketoconazole

Polyene

Level 3

Level 3

Level 3

Level 3

Level 3

Fluc: Some candida species,

Decreased drug concentration
Target site alteration
Up-regulation of target enzyme
Development of bypass pathways

potent CYP inhibitors with a wide range of drug interactions (including warfarin)