Zidovudine Comprehensive Study Guide With Accurately Solved Questions.

Pharmacotherapeutics - correct answer Zidovudine is active against the Epstein-Barr virus and hepatitis B virus (HBV) and exerts some antibacterial activity against Enterobacteriaceae, but its main indication is for treating HIV infection in adults and children and preventing transmission on HIV to the fetus in pregnant HIV positive women. The symptomatic patients should start therapy regardless of laboratory values. The recommendation for initiating treatment in asymptomatic patients is a CD4 cell count between 200-350 cell/mm, or those with HIV nephropathy, or patients with active HBV with the intent to treat HBV. Pharmacokinetics - correct answer Zidovudine (AZT) is administered orally or parenterally. Following oral administration, zidovudine is absorbed rapidly from the tract. The rate and extent of drug absorption may be decreased by fatty meats. The half-life of zidovudine is 1 hour in patients with normal renal function and increases to 1.4 to 2.9 hours in patients with renal dysfunction. Hepatic dysfunction also causes a moderate prolongation of zidovudine half-life. It crosses the blood brain barrier and placenta. It is converted into zidovudine triphosphate, its active form, by intracellular conversion and irs inactive metabolite by the liver. Both active drug and inactive metabolite are excreted by glomerular filtration and tubular secretion. It is now available in fixed dose combination in one pill, with lamivudine or abacavir. Pharmacodynamics - correct answer Zidovudine inhibits the synthesis of DNA by reverse transcriptase Zidto ovudine bears a structural resemblance to thymidine, a natural nucleoside. Reverse transcriptase fails to distinguish zidovudine from its natural counterpart, and the enzyme attempts to use the drug to synthesize vial DNA. When zidovudine is incorporated into a stand of DNA, the addition of further nucleotides is blocked, and the full length viral DNA chain is prematurely terminated. Contraindications and Precautions - correct answer Absolute contraindications to the use of zidovudine include hypersensitivity, breast-feeding, and existing lactic acidosis. Patients with preexisting hepatic dysfunction, obesity, and prolonged nucleoside analogue therapy have a higher risk of developing lactic acidosis due to the association of NRTIs to liver mitochondrial toxicity. Zidovudine should be given with caution to patients with pre-existing depression of bone marrow function, folate deficiency, or vitamin B12 deficiency. Patients with these disorders are at increased risk for severe hematologic toxicity. It is also given with caution to patients who have recently received cytotoxic drugs or radiation therapy because it may induce myelosuppression. Because of the risk of myelosuppression, patients with dental disease are also given zidovudine with caution. Zidovudine should be given with caution in patients with hepatic or renal disease. In patients with impaired hepatic function or renal function, it may accumulate. Adverse Effects - correct answer GI symptoms include nausea and vomiting, diarrhea, abdominal pain, dyspepsia, and anorexia. Esophageal ulceration also has occurred. CNS effects have been reported including headache, seizures, somnolence, paresthesias, agitation, restlessness, and insomnia. Other adverse effects that have been described include nail discoloration, rash, and alteration in taste. Drug/Dietary Interactions - correct answer The most important drug interaction is with ganciclovir, a medication used to treat cytomegalovirus retinitis , a late opportunistic infection seen with HIV infection, which may induce life-threatening hematologic toxicity. Other drugs that interact with zidovudine include acetaminophen, interferon beta-1 b, probenecid, rifampin, trimethoprim, and valproic acid. Assess the patient's typical dietary habits. Although zidovudine is taken without regards to meals, avoidance of fatty foods is important because these foods decrease the drug's absorption. Outline a high-carbohydrate, moderate-protein