P1: PSB Printer: Yet To Come
9780521704632c22 CUFX213A/Peck 9780521618168 December 29, 2007 14:51
Section IVOther important drugsKinetics
Intestinal absorption is erratic and the oral bioavailability is low at approximately
25%. Acyclovir is widely distributed with 15% being protein bound. It is partially
metabolized to inactive compounds but largely undergoes active tubular excretion
unchanged into the urine, but this can be blocked by probenecid. Dose reduction
in renal failure is required and a dose of 3.5 mg.kg−^1 .day−^1 has been suggested for
patients on CVVHDF.Side effects
Renal – rapid intravenous administration may precipitate renal impairment.
Thrombophlebitis – it is highly irritating to veins and may cause ulcers when
extravasated.
Central nervous system – tremors, confusion, seizures and coma during rapid
intravenous administration are recognized.Zidovudine
Zidovudine is used to treat the human immunodeficiency virus (HIV) in combination
with other antiviral agents.Mechanism of action
Zidovudine is a nucleoside reverse transcriptase inhibitor (or nucleoside analogue)
that is converted by various kinase enzymes to zidovudine triphosphate, the active
compound. This binds to HIV-reverse transcriptase and when it becomes incorpo-
rated into proviral DNA chain termination occurs. Its affinity for HIV-reverse tran-
scriptase is 100 times greater than for host DNA polymerase.Kinetics
Zidovudine is given orally or intravenously and distributes widely. It is transported by
the choroid plexus into the CSF where levels are 50% plasma levels. It is conjugated
in the liver and up to 80% is excreted in the urine as the glucuronide. Accumulation
occurs in renal failure and dose reduction is required. Patients on CVVHDF should
receive doses at the lower end of the dosage range.Side effects
Haematological – anaemia and neutropenia.
Gut–gastrointestinal upset, anorexia, deranged liver function, steatorrhoea and
lactic acidosis.
Miscellaneous – headache, myalgia, parasthesia and pigmentation of nail beds and
oral mucosa.