Pharm small group: HIV 1 Flashcards
Describe the MOA of NRTI’s
- Competitive inhibition of HIV-1 reverse transcriptase
- Incorporation of the drug into viral DNA chain -> premature chain termination due to inhibition of binding with incoming nucleotide.
NRTI’s require what for activation?
-Intracytoplasmic activation via PHOSPHORYLATION by cellular enzymes to the triphosphate
Do NRTI’s have activity against HIV 2?
Yes.. most. Along with HIV-1 (who knew)
How do NRTI’s cause mitochondrial toxicity?
Inhibit mitochondrial DNA polymerase gamma
Which NRTI’s have the highest affinity for mitochondrial DNA polymerase gamma and are thus avoided for HIV treatment? (2)
1) Didanosine
2) Stavudine
Mitochondrial toxicity is the major cause of what adverse effects by NRTI’s? (4)
1) Myopathy
2) Peripheral Neuropathy
3) Lipoatrophy
4) Lactic acidosis
Which NRTI is associated with Bone Marrow Suppression in individuals with advanced HIV disease?
Zidovudine
Zidovudine concurrently administered with which drug results in additive neutropenia?
Gangiclovir
Describe the MOA of NNRTI’s
-Bind directly to HIV-1 reverse transcriptase -> allosteric inhibition of RNA and DNA dependent DNA polymerase.
Do NNRTI’s work against HIV-2?
Apparently not.
In general, what are the adverse effects of NNRTI’s?
GI intolerance and skin rash -> STEVENS JOHNSON SYNDROME
What are the main adverse effects of Efavirenz? (5)
CNS:
1) Dizziness
2) Impaired concentration
3) Dysphoria
4) Insomnia
5) Psychosis
-Generally resolve within first 4 weeks of therapy
NNRTI’s are substrates of what?
CYP3A4
Which NNRTI’s induce CYP3A4?
Nevirapine
Which NNRTI’s inhibit CYP3A4?
Delavirdine
