Acyclovir, valacyclovir, and famciclovir are nucleoside analogs, used for the treatment of herpes simplex and varicella zoster infections. These drugs have similar mechanisms of action and comparable clinical indications. Acyclovir is a guanosine nucleoside analog, which requires conversion to acyclovir triphosphate to inhibit viral RNA polymerase and, eventually, halt viral DNA synthesis. This conversion comprises three phosphorylation steps, the first being conducted selectively in virus-infected cells by virus-encoded thymidine kinase.
Thymidine kinase, an important part of acyclovir's activation, can also be a source of viral resistance to the drug. However, drugs like cidofovir and foscarnet are not subject to this weakness, and can be used for treating resistant strains. Notably, valacyclovir, an acyclovir prodrug, has better oral bioavailability than acyclovir. Acyclovir is unique as it is also available for IV use in the United States and is used to treat serious infections including herpes simplex encephalitis and neonatal HSV infection.
In terms of treating herpes zoster infections, acyclovir, valacyclovir, and famciclovir are all effective, but the latter two are usually preferred due to superior activity and less frequent dosing. These drugs are also used for daily suppressive therapy in patients with recurring herpes infections and in immunocompromised patients for prevention of herpes infections. Worth noting are potential side effects including renal impairment from IV administration of acyclovir and potential central nervous system effects like delirium, confusion, vertigo, and hallucinations.
Acyclovir, valacyclovir, and famciclovir are guanine nucleoside analogs that inhibit replication of the herpes simplex virus (HSV). They are initially converted to their monophosphate forms via the virus encoded thymidine kinase, then further converted to their triphosphate forms by cellular kinases. These triphosphates can then incorporate into the replicating viral DNA, effectively halting synthesis and thus preventing the virus from reproducing.
Resistance to acyclovir, valacyclovir, and famciclovir can occur due to the absence of thymidine kinase, which is essential for their activation and incorporation into viral DNA. In these cases, the drugs are unable to halt the synthesis of viral DNA, meaning that the virus can continue to replicate despite the presence of the medication.
For HSV that is resistant to acyclovir or ganciclovir, cidofovir and foscarnet are potential alternative treatments. These drugs do not require phosphorylation by viral thymidine kinase to be activated and thereby avoid that source of resistance.
For infections caused by the varicella zoster virus, such as shingles, famciclovir and valacyclovir are generally the preferred treatments due to their superior activity and less frequent dosing requirements. They are most effective if given within three days of the onset of symptoms.
Intravenous acyclovir can cause renal side effects such as interstitial nephritis or crystalline nephropathy. To help prevent these side effects, it is important to ensure adequate hydration. Other possible adverse effects include delirium, confusion, vertigo, and hallucinations.