Antiretrovirals Flashcards
What do the NRTIs do?
- act as faulty building blocks in production of viral DNA synthesis = competitive inhibitors
- nucleosides must be phosphorylated by host enzymes
What drugs are NRTIs?
Zidovudine, Abacavir, Lamivudine, Tenofovir, Emtricitabine (TAZEL drugs Razzle your mitochondria)
What are the general toxicities for the NRTIs?
mitochondrial toxicity and lactic acidosis
What resistance would occur for the NRTIs?
change in RT or inability to phosphorylate prodrug
What are all AE of NRTIs?
fat redistribution, hyperlipidemia, hepatomegaly (hepatic steatosis), lactic acidosis
What are the specific toxicities for AZT (zidovudine)?
anemia and granulocytopenia
What are the specific toxicities for abacavir?
hypersensitivity
What are the specific toxicities for tenofovir?
most renal toxic of the ART drugs
What drug is an integrase inhibitor?
raltegravir
What is the action of raltegravir?
inhibit integrase –> virus cannot be integrated into host genome –> no viral replication
What is the resistance to raltegravir?
change integrase enzyme
What are the toxicities related to raltegravir?
drug interactions
What ART drugs have drug-drug interactions?
Non-NRTIs, protease inhibitors, integrase inhibitor (raltegravir)
What is the general action of the protease inhibitors?
bind the active site of protease –> can’t cleave gag-pol-env polyprotein
What drugs are protease inhibitors?
Ritonavir, Atazanavir, Darunavir
If you are a pro at something, you’re probably pretty RAD
What are the general toxicities associated with the protease inhibitors?
drug interactions, peripheral lipoatrophy and central fat accumulation
RAD to have skinny arms and fat gut
What is the major function of Ritonavir?
inhibits Cyp450 –> used in conjunction with other protease inhibitors to increase their concentration
What is the general action of the entry/fusion inhibitors?
block virus from entering cell by blocking host receptor or viral env proteins
What is the major downside of entry/fusion inhibitors?
must be administered through injection - tough to get compliance
What drugs are entry/fusion inhibitors?
Maraviroc, Enfuvirtide
What is the action of Maraviroc?
CCR5 receptor antagonist that blocks viral gp120 from associated with its receptor
-is blocking HOST protein
What must be done before Maraviroc is administered?
trofile assay to determine viral tropism - virus could use CXCR4 to enter cells rather than CCR5
What is the action of Enfurvirtide?
inhibits conformational change in viral gp41 that is required for HIV entry
What is the general action of NNRTIs?
directly bind RT and inhibit its action –> no copies of viral DNA made
- act directly on enzyme unlike NRTIs
- allosteric inhibitors, don’t bind active site
