![]() ![]() Researchers have discovered more than 50 CYP450 enzymes, but the CYP1A2, CYP2C9, CYP2D6, CYP3A4, and CYP3A5 enzymes account for the metabolism of up to 90% of drugs that undergo this type of biotransformation. Their name is derived from being bound to membranes within a cell (cyto) and contain a heme pigment that absorbs light at a wavelength of 450 nm (chrome) when exposed to carbon monoxide. The active site of cytochrome P450 contains a heme center. Essential for the production of cholesterol, steroids, prostacyclins, and thromboxane A 2, cytochrome Ps (CYPs) are the major enzymes involved in drug metabolism, accounting for approximately 75% of the total metabolism of all drugs. As will be discussed later, due to genetic variation in CYP450 and to the potential for drug interactions, these later five agents have significant risks for wide serum level variation.ĬYP450 enzymes are present in many tissues of the body, including the endoplasmic reticula in hepatocytes, intestinal mucosa, lungs, brain, and kidney. The CYP450 system is of major significance in the metabolism of codeine, fentanyl, methadone, oxycodone, and oxymorphone. The UGTs are a secondary metabolizing system responsible for the formation of glucuronides and have a major role in the metabolism of hydromorphone, morphine, and oxymorphone. CYP450 Enzyme SystemĪll opioids are metabolized through two major enzyme systems, CYP450 and, to a lesser extent, by the UDP-glucuronosyltransferases (UGTs) with a specific affinity for the UGT2B7 isozyme. This review will focus on the effect of the cytochrome P450 (CYP450) enzyme system metabolism on opioid agents such as codeine, fentanyl, hydrocodone, hydromorphone, methadone, morphine, oxycodone, and oxymorphone, as well as the potential effect of these opioids on the metabolism of other medications and vice versa. An understanding of the metabolism of opioids will assist practitioners in avoiding clinically significant and dangerous interactions. While much of the research has focused on tricyclic antidepressants, selective serotonin reuptake inhibitor antidepressants, first-generation anticonvulsants (e.g., carbamazepine and phenytoin), and methadone, recently there has been a heightened interest in the unique and specific metabolism and thereby potential drug interaction risks of various opioid agents. Over the past 10–20 years, researchers have enhanced our understanding of the metabolism and risk of drug interactions of numerous medications utilized by patients with pain conditions. It has been estimated that 75% of adverse reactions are related to interactions that increase or decrease the amount or action of the drug in the body by the presence of another drug or multiple drugs affecting its metabolism. Some data suggest that the risk of a drug–drug interaction increases with number of medications used, occurring in 13% of patients taking two medications and 82% of patients taking more than six medications. Polypharmacy, a term that describes the use of multiple medications in patients, can be a concern due to overlapping toxicities and increased risk of drug–drug interactions secondary to altered metabolism. Many patients with pain are prescribed multiple pharmacological interventions, often administered concurrently. Cytochrome P450, Drug Interactions, CYP3A4, CYP2D6, Metabolites, Opioids Introduction ![]()
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