False about protease inhibitors in HIV is
Of all the protease inhibitors saquinavir is the most powerful inhibitor of CYP3A4 Protease inhibitors:- Protease inhibitors constitute a new class of agent for HIV infection. In its process of replication, HIV produces a protein and also a protease which cleaves the protein into component pas that are subsequently reassembled into virus paicles. Protease inhibitors have been shown to reduce viral RNA concentration, increase the CD4 count and improve survival when used in combination with other agents. Examples of protease inhibitors are:? Indinavir Nelfinavir Saquinavir Ritonavir Lopinavir Pharmacokinetics of protease inhibitors are:? All HIV protease inhibitors are both substrates and inhibitors of CYP isoforms (family of P-450 isoenzymes) All the protease inhibitors undergo oxidative metabolism by CYP3A4. The metabolism occurs predominantly in liver. All the protease inhibitors are inhibitors of CYP isoforms The rank order of CYP3A4 inhibitor potency is ritonavir > (indinavir, amprenavir, nelfinavir > saquinavir). All HIV protease inhibitors are also substrates for P-glycoprotein, the multidrug efflux pump encoded by MDR-1. - This suggests that cells in the patient that express MDRI transpoer will be relatively, resistant to protease inhibitors. More about protease inhibitors Oral bioavailability of indinavir is decreased by food. It can cause thrombocytopenia and kidney stones. To prevent renal damage good hydration must be maintained. Side effects of Protease inhibitors Diabetes (hyperglycemia, insulin resistance) Lipodystrophy (hyperlipidemia, redistribution of body fat) Liver toxicity (less common side effect).
They are powerful enzyme inhibitors
Of all the protease inhibitors saquinavir is the most powerful inhibitor of CYP3A4
They cause hepatic toxicity
All protease inhibitors are substrates for P glycoprotein coded by MDR gene