Hersh Elliot V, Moore Paul A
University of Pennsylvania School of Dental Medicine, Philadelphia 19104-6030, USA.
J Am Dent Assoc. 2004 Mar;135(3):298-311. doi: 10.14219/jada.archive.2004.0178.
The hepatic and intestinal cytochrome, or CY, P450 enzyme system is responsible for the biotransformation of a multitude of drugs. Certain medications used in dentistry can act as substrates, inducers or inhibitors of this system.
The authors conducted a MEDLINE search of articles appearing between 1976 and the present using the keywords "drug interactions" and "cytochrome P450," and reviewed reports involving dental therapeutic agents using PubMed links from an Indiana University CYP450 drug interaction table on the World Wide Web.
The antibiotics erythromycin and clarithromycin are potent inhibitors of CYP3A4 and can increase blood levels and toxicity of CYP3A4 substrates. Likewise, quinolone antibiotics such as ciprofloxacin inhibit the metabolism of CYP1A2 substrates. Other dental therapeutic agents are substrates for CYP2C9 (celecoxib, ibuprofen and naproxen), CYP2D6 (codeine and tramadol), CYP3A4 (methylprednisolone) and CYP2E1 (acetaminophen). Because codeine and tramadol are prodrugs, inhibition of their metabolism can lead to a diminution of their analgesic effects. While inducers of acetaminophen metabolism, including alcohol, theoretically can increase the proportion of it that is biotransformed into a potentially hepatotoxic metabolite, recent research suggests that concomitant alcohol intake does not increase the hepatotoxic potential of therapeutic doses of acetaminophen.
A number of clinically significant drug interactions can arise with dental therapeutic agents that act as substrates or inhibitors of the CYP450 system. Clinical Implications. As polypharmacy continues to increase, the likelihood of adverse drug interactions in dentistry will increase as well. Ensuring that patients' medical histories are up to date and acquiring knowledge of the various substrates, inducers and inhibitors of the CYP450 system will help practitioners avoid potentially serious adverse drug interactions.
肝脏和肠道中的细胞色素（CY）P450酶系统负责多种药物的生物转化。牙科中使用的某些药物可作为该系统的底物、诱导剂或抑制剂。
作者使用关键词“药物相互作用”和“细胞色素P450”对1976年至当前发表的文章进行了MEDLINE检索，并通过万维网上印第安纳大学CYP450药物相互作用表中的PubMed链接，回顾了涉及牙科治疗药物的报告。
抗生素红霉素和克拉霉素是CYP3A4的强效抑制剂，可提高CYP3A4底物的血药浓度和毒性。同样，喹诺酮类抗生素如环丙沙星可抑制CYP1A2底物的代谢。其他牙科治疗药物是CYP2C9（塞来昔布、布洛芬和萘普生）、CYP2D6（可待因和曲马多）、CYP3A4（甲泼尼龙）和CYP2E1（对乙酰氨基酚）的底物。由于可待因和曲马多是前体药物，抑制它们的代谢会导致其镇痛效果减弱。虽然包括酒精在内的对乙酰氨基酚代谢诱导剂理论上可增加其转化为潜在肝毒性代谢物的比例，但最近的研究表明，同时摄入酒精并不会增加治疗剂量对乙酰氨基酚的肝毒性潜力。
作为CYP450系统底物或抑制剂的牙科治疗药物可引发一些具有临床意义的药物相互作用。临床意义。随着联合用药的持续增加，牙科中药物不良相互作用的可能性也会增加。确保患者的病史最新，并了解CYP450系统的各种底物、诱导剂和抑制剂，将有助于从业者避免潜在的严重药物不良相互作用。
