Antiretrovirals and antianemic agents Flashcards
Name the four different types of HIV treatments?
- RT inhibitors
- Protease inhibitors
- Fusion inhibitors
- Integrase inhibitors
Describe the mechanism of action for nucleoside RT inhibitors
- Must be phosphorylated in the cell in order to become active
- Inhibit by being incorporated into the DNA preventing further transcription
- This is done by lacking 3’ OH
What are common NRTI’s and how are they excreted?
- Most excreted renally except
- Zidovudine (AZT) - glucuronidation
- Abacavir (ABC) - alcohol dehydrogenased
- No P450 drug interactions
What is the toxicity concern with NRTI’s and there effects clinically?
- Mitochondrial toxicity
- Hepatic failure with steatosis (fatty liver) and lactic acidosis.
What are the 2 NRTI resistance mechanisms?
- Nulceoside analog descrimination
- Primer nucleoside unblocking- excision
What is the mechanism of non-nulceoside RT inhibitors?
- Bind directly to RT enzyme preventing transcription
What are the 5 NNRTI’s?
- Efavirenz
- Delavirdine
- Etravirine
- Nevirapine
- Rilpivirine
What are the advantages and disadvantages of NNRTI’s?
- Adv- long half-life, Hepatic metabolism no renal function adjustments required
- Disadv -resistance and cross resistance
- Skin rash, increased transaminase levels and P450 interactions
Protease inhibitor info
- All end in navir
- Ritonavir induces own metabolism (most potent 3A4 INH) and is often use along with other PI’s to reduce metabolism
What are the PI advantages and disadvantages?
- Adv - higher barrier to resistance
- Disadv - Dyslipidemia, insulin resistance, and hepatotoxicity, GI effects, drug interactions
What is the mechanism of action of fusion inhibitors?
- Bind to CD4 on cell surface (MIraviroc) or surface of the HIV envelop (Enfuvirtide)
What are the adverse effects of Miraviroc?
- Hepatotoxicity preceded by allergic reaction (rash and eosinophilia)
- CV adverse effects
- Dizziness and postural hypotension
What is the mechanism of action for integrase inhibitors?
- Binds pre-integration complex to the host DNA
- Terminating integration of viral DNA to the host genome
Name two integrase inhibitors
- Raltegravir (BID)
- Elvitegravir (Q day)
What is cobistat?
- CYP3A4 inhibitor given with elvitegravir to allow single dose.
