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The U.S. Food and Drug Administration (FDA) notified healthcare professionals of updates to the prescribing information concerning interactions between protease inhibitors and certain statin drugs. Protease inhibitors and statins taken together may increase the blood levels of statins and increase the risk for muscle injury (myopathy).
Statine is a gamma amino acid that occurs twice in the sequence of pepstatin, a protease inhibitor that is active against pepsin and other acid proteases. [1] It is thought to be responsible for the inhibitory activity of pepstatin because it mimics the tetrahedral transition state of peptide catalysis.
Protease inhibitors were the second class of antiretroviral drugs developed. The first members of this class, saquinavir , ritonavir , and indinavir , were approved in late 1995–1996. Within 2 years, annual deaths from AIDS in the United States fell from over 50,000 to approximately 18,000 [ 5 ] Prior to this the annual death rate had been ...
Risk factors for statin induced rhabdomyolysis include older age, renal impairment, high dose statins and use of medications that reduce the breakdown of statins (such as CYP3A4 inhibitors) or fibrates. [66] Persistent liver enzyme abnormalities (usually elevated in hepatic transaminases) have been documented. [67]
Pepstatin A is well known to be an inhibitor of aspartic proteases such as pepsin, cathepsins D and E. Except for its role as a protease inhibitor, however, the pharmacological action of pepstatin A upon cells remain unclear. Pepstatin A suppresses receptor activator of NF-κB ligand (RANKL)–induced osteoclast differentiation.
Another example, aprotinin, is a naturally-occurring broad-spectrum protease inhibitor; [2] some countries refuse to approve this medication because it supposedly has a greater mortality rate than its alternatives (tranexamic acid and aminocaproic acid) and causes damage to the kidneys and heart. It is widely agreed that systemic aprotinin use ...
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However, when present in a high enough concentration to counteract the effects of plasminogen activator inhibitor, tPA can bind plasminogen, cleaving off the bound plasmin from it. Plasmin, another type of protease, can either be bound by a plasmin inhibitor, or work to degrade fibrin clots, which is the main therapeutic pathway. [37]