Antimicrobial pharmacology 3

Question 1

What are the 3 classes of antiviral agents based on target organisms?

Answer 1

• Nucleoside and nucleotide reverse transcriptase inhibitors - NsRTIs and NtRTIs
• Non-nucleoside reverse transcriptase inhibitors - NNRTIs (1st generation and 2nd generation)

Question 2

What is the mechanism of action of NsRTIs and what is their use in HAART?

Answer 2

• antimetabolite drugs - interferes with the metabolism and development of the DNA particle or the RNA transcription.
• We use 3 or more drugs at the same time for HIV treatment - HAART (HIghly active antiretroviral treatment)
• multi-drug regimen - reduce or reverse the decrease of CD4 counts
• NsRTs act on the viral transcriptase (which is different from the mammalian reverse transcriptase) - fewer side effects for the host
• The NSRTIs lack a 3’ Prime hydroxyl group on the ribose ring so that the next nucleotide can’t bind to that chain the NSRTIS are converted by the host cell kinase to triphosphates that block the binding of the nucleotides to the D site of the reverse transcriptase and they act as a chain terminator.

Adverse effects:
- lactic acidosis
- hepatomegaly (watch aminotransferase levels)
-

Question 3

What are some examples of non-nucleoside reverse transcriptase inhibitors? (NNRTIs)

Answer 3

1st gen - efavirenz, neviripine, and delaviridine

Question 4

What are the toxicity and side effects of first-generation NNRTIs?

Answer 4

• Efavirenz
• given once a day
• metabolized by cytochrome and drug interactions are common with this medication
• Toxicity and side effects:
• typical neurological symptoms - CNS dysfunction
• peripheral neuropathies
• dermatological reactions - skin rash
• Don’t use this medication in pregnancies- potentially teratogenic in the first semester
• can increase serum cholesterols or blood cholesterols

Question 5

What is the mechanism of action of integrase strand transfer inhibitors (INSTIs)?

Answer 5

• integrase helps viral DNA gets integrated into the host DNA - an important part of the replication cycle

Not metabolized through the cytochrome system but it does undergo glucuronidation.