Activation

• Acyclovir requires three phosphorylation steps for activation.

• It is converted first to the monophosphate derivative by the virus specific thymidine kinase and then to
the di- and triphosphate compounds by host cell
• Inhibition of viral DNA synthesis

Two mechanisms: – competition with deoxy GTP for the viral DNA polymerase, resulting in binding to
the DNA template as an irreversible complex; and chain termination following incorporation into the
viral DNA.

Active against all Herpes viruses & CMVLow oral bioavailability given I.V.Most common A/E: bone
marrow suppression (leukopenia, thrombocytopenia ) and CNS effects (headache, psychosis,
convulsions).1/3 of patients have to stop because of adverse effects

Foscarnet should only be given during pregnancy when benefit outweighs risk
Must be administered with high-dose probenecid & adequate hydration

Antiretroviral Drugs HAART - Highly active antiretroviral therapy

Includes at least three medications“cocktails”These medications work in different ways to reduce the
viral load

• Mechanism of action – NRTIs act by competitive inhibition of HIV-1 reverse transcriptase –

Incorporation into growing viral DNA chain causes premature chain termination due to inhibition of
binding with the incoming nucleotide • Status of NRTIs – Considered as “backbone” of the
antiretroviral therapy – Used with other agents (NNRTI, PI, or II) – NRTI itself given in pairs but
certain combinations should be avoided due to drug interactions, similar resistance patterns or
overlapping toxicities

42 slide. All NRTIs may be associated with mitochondrial toxicity, lactic acidosis with fatty liver
may occur, which can be fatal. Zidovudine and Stavudine : dyslipidemia and insulin resistance.
Increased risk of myocardial infarction in : Abacavir or Didanosine

This study source was downloaded by 100000818316582 from CourseHero.com on 02-04-2023 04:27:21 GMT -06:00

https://www.coursehero.com/file/188681182/Activationdocx/
Powered by TCPDF (www.tcpdf.org)