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Protease Inhibitors

Antiretroviral

QuestionAnswer
protease inhibitors (PI) inhibit HIV enzymes for maturation of HIV to a fully functional virus = produce immature nonfunctional, non infectious virus; no activation, affected by food, short half live, high PRO binding, inhibit CYP3A4(high drug-drug interactions)
Protease responsible for cleaving immature budding particles to produce final structural proteins of the mature virion core
Protease mutations broad resistance to substitutions at the 10, 46, 54, 82, 84, and 90 codons
Protease adverse events dyslipidemia, lipodystropy, hyperglycemia, dorsocervical fat enlargement(buffalo hump), central obesity,peripheral/facial wasting, breast enlargement,cushing appearance, GI effects
Can lead to redistribution and accumulation of body fat protease inhibitors
Cushing appearance protease inhibitors
Protease inhibitors atazanavir, darunavir, fosamprenavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, tipranavir
Ritonavir PI, boosting effect,metabolize in liver, inhibit CYP3A4(high drug-drug interactions), 3-5 hrs,NVD, paresthesias, HA, altered taste, abdpain,increase creatine kinase, long QT/PR
Atazanavir PI, need light meal to increase PO absorption, need acidic medium for absorption, excretion:liver(biliary), NVD, abdpain,HA,skin rash, peripheral neuropathy, nephrolithiasis, DO NOT CAUSE FAT REDISTRIBUTION(RITONAVIR), long PR/QT/AV block, avoid with PPI
Darunavir PI, must be co-administered with Ritonavir (booster), NVD,HA,rash,dyslipidemia,hepatotoxcitiy, severe hepatitis, increase amylase/lipase, caution w/pts w/sulfonamide allergy r/t contains sulfa component, inhibit CYP3A4
Fosamprenavir prodrug of amprenavir PI, take w/food or not(no fatty foods), administer in combo w/low dose ritonavir, long halflife,metabolize in liver by CYP3A4, HA,NVD,rash,depression,perioral paresthesias, inducer/inhibitor of CYP3A4,contains sulfa,vitamin E,propylene glycol(use caution)
Indinavir PI,acidic,take on empty stomach or w/small lowfat/PRO meal,excreted fecal,indirect hyperbilirubinemia/nephrolithiasis, insulin resistance,thrombocytopenia,NVD,insomnia,dry throat,dry skin, consume 48oz of water daily to maintain hydration, inhibit CYP3A4
Lopinavir PI, used combo w/ritonavir, take w/ food, highly PRO bound, half-life 5-6hrs, metabolize by CYP34(inhibited by ritonavir), NVD,abdpain,asthenia,increase TG/cholesterol
Nelfinavir PI, high absorption, metabolism CYP3A, excreted feces, highly PRO-bound, half-life 3.5-5hrs,diarrhea/flatulence, inhibit CYP3A, good for PG women
Saquinavir PI, take 2 hrs after fatty meal, half-life 2 hrs, protein-bound, excreted in feces, NVD, abd pain, dyspepsia, rhinitis,long QT/PR, first pass metabolism by CYP3A4, check LFT
Tipranavir PI, new, combo w/ritonavir, poor absorption, but increase w/fatty meal, metabolize by liver, contains sulfa, NVD, abdpain, rash, liver toxicity, intracranial hemorrhage, depression, increase amylase, decrease WBC, inhibit and induce CYP3A4
Created by: cburrows
 

 



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