zidovudine

INTRODUCTION:
  • Zidovudine is frequently used NRTI in the treatment of HIV infections. It can also be used for the prophylaxis of needle stick injury patients and for the prevention of vertical transmission of HIV from mother to fetus.
  • Zidovudine, a structural analog of thymidine, is a prodrug that must be phosphorylated to its active 5′-triphosphate metabolite, zidovudine triphosphate (ZDV-TP).
  • Zidovudine + Lamivudine+Nevarapine drugs are supplied free of cost to the government Hospital by NACO 
INDICATIONS:
  • Used in combination with other antiretroviral agents for the treatment of human immunovirus (HIV) infections
  • Human Immunodeficiency Virus (HIV) Infections
  • Perinatal HIV transmission:Zidovudine for mother (36 weeks) and child (6 weeks)
  • Post exposure HIV transmission:Zidovudine + Lamivudine + Indinavir for 4 weeks
MECHANISM OF ACTION:
  • It inhibits the activity of HIV-1 reverse transcriptase (RT) via DNA chain termination after incorporation of the nucleotide analogue.
  • It competes with the natural substrate dGTP and incorporates itself into viral DNA. It is also a weak inhibitor of cellular DNA polymerase α and γ
ADVERSE EFFECT:
  • Major adverse effect of zidovudine is bone marrow suppression leading to megaloblastic anemia and thrombocytopenia. 
  • It can also cause myopathy. 
  • Severe hepatotoxicity associated with steatohepatitis, most likely a result of mitochondrial toxicity, is being recognized with increasing frequency with antiretroviral therapy with reverse transcriptase inhibitors (e.g., zidovudine, didanosine) or protease inhibitors (e.g., indinavir, ritonavir.
DRUG INTERACTIONS:
  • Drugs that inhibit hepatic glucuronidation, such as indomethacin, acetylsalicylic acid (Aspirin) and trimethoprim, decrease the elimination rate and increase the toxicity.
  • Other nephrotoxic drug and myelosuppressive drugs and probebecid enhances toxicity.
  • Stavudine and zidovudine exhibit mutual antagonism by competing for the same activation pathway.
Exam Question
  • Zidovudine for mother (36 weeks) and child (6 weeks) therapy can be offered to reduce the chance of transmission of HIV to the newborn 
  • Zidovudine causes myopathy as side effect
  • Severe hepatotoxicity associated with steatohepatitis, most likely a result of mitochondrial toxicity, is being recognized with zidovudine
  • Zidovudine + Lamivudine + Indinavir for 4 weeks is the recommended regimen for post exposure prophylaxis of HIV Infection
  • Resistance to zidovudine develops due to Mutations at reverse transcriptase
  • Zidovudine + Lamivudine+Nevarapine drugs are supplied free of cost to the government Hospital by NACO 
  • Co-administartion of Indomethacin ,Aspirin & Trimethoprim are not preferred with zidovudine
Don't Forget to Solve all the previous Year Question asked on zidovudine