抗生素(英文精品) A focus on drug interaction幻灯片课件.pptVIP

* These are the important inhibitors of CYP3A that will cause patients to appear phenotypically similar to poor metabolizers. In general, azole antifungal drugs are potent inhibitors of CYP3A, although fluconazole, a potent inhibitor of CYP2C9, is a relatively weak inhibitor of CYP3A, even at high doses. All the macrolide antibiotics, except azithromycin, are also potent inhibitors of this cytochrome P450. Cimetidine, unlike ranitidine, is a broad, but relatively weak, inhibitor of many cytochrome P450 enzymes. Also, notice that grapefruit juice is listed as an inhibitor. The role of grapefruit juice in drug interactions will be discussed later in this program. * Several commonly used drugs have been characterized as inducers of CYP3A. Use of these drugs could potentially result in lack of therapeutic efficacy of drugs metabolized by CYP3A. For example, drug interactions with the herbal preparations containing St. John’s wort will be discussed later in the presentation. * CYP2D6 metabolizes many of the cardiovascular and neurologic drugs in use today. Clinical investigation of CYP2D6 has led to understanding of the reason that codeine fails to relieve pain in some patients. Codeine is actually a pro-drug that is converted to morphine. Codeine itself has only weak analgesic activity and often causes nausea and other adverse effects. The absence of cytochrome P450 2D6 activity in 7 to 9% of many populations means that these individuals cannot metabolize codeine to form the active metabolite morphine. Therefore, they get little, if any, pain relief from codeine.1 Unfortunately, they will experience codeine’s adverse effects, particularly if the dose is increased in the futile attempt to relieve pain. In a study of Ethiopians, thirty percent were found to have multiple copies (up to 13) of the 2D6 gene and had increased enzyme activity resulting in ultra-rapid metabolism.2, 3 Ultra-rapid metabolism results in lower blood levels following a standard dose