BIIC Pharmacology Lecture 6_HIV Pharmacology Flashcards
What is the protocol for HIV combination therapy?
(2) NRTIs with one of the following: • Integrase inhibitor • NNRTI • Protease inhibitor (PI) boosted with CYP450 inhibitor ritonavir or cobicistat
What are the 6 general principles for establishing HIV combination therapy?
- Avoid using agents of the same nucleoside analog
- Avoid drugs with overlapping toxicities
- Choose drugs appropriate to genotypic and phenotypic
characteristics of the virus (E.g., strain type, resistance - Consider patient factors, including disease symptoms and
concurrent illnesses - Impact of drug interactions
- Ease of adherence to the regimen
What drug combo cannot be used in patients that are HLA-B*5701 positive?
Dolutegravir/abacavir/lamivudinea
Which two NTRIs most often result in Lipoatrophy and insulin resistance?
stavudine and zidovudine
What are two draw backs of NNRTIs
Resistance develops rapidly and they are only active against HIV-1. On the up side, they have no activity against host DNA ploymerase
How are NRTIs metabolised?
Renally
How are NNRTIs metabolised?
hepatically by CYPs
What is unique about Enfuvirtide?
It is a polypeptide so it must be injected. it binds GP41 and prevents penitration to host cell
What are the two main PIs?
- Atazanavir
* Darunavir
What are the common “significant” ADRs of PIs
insulin resistance and Fat redistribution
What drugs are contraindicated with PIs?
• simvastatin, lovastatin (statins): rhabdomyolysis
• midazolam, triazolam (benzos): excessive sedation
• fentanyl: respiratory depression
• rifampin, St. John’s Wort: reatment failure due to induction of CYP
enzymes
How does ritonavir enhance Pharmacokinetics
A potent CYP3A4 inhibitor, CYP2D6, can be used to elevate levels of second PI
How does Cobicistat enhance Pharmacokinetics
Inhibits CYP3A4 (and CYP3A isoenzymes), CYP2D6 and P-gp (increases bioavalability of atazanavir and darunavir)
What is the MOA of Integrase Inhibitors?
• Integrase enzyme function requires two divalent cations • INSTIs chelate these cations • Antacids or other polyvalent cations should be avoided (dairy)
What is the ADR of Raltegravir
rare but life-threatening rhabodmyolysis
