Baciewicz A M, Baciewicz F A
Department of Pharmacy Services, University Hospitals of Cleveland, OH 44106.
Am Heart J. 1989 Jul;118(1):144-54. doi: 10.1016/0002-8703(89)90085-9.
A compilation of drug interactions between H2 antagonists and cardiovascular drugs is found in Table I. Cimetidine's potency, lipophilicity, and affinity for binding to the P-450 cytochrome system can probably be attributed to the drug interactions that have been identified with the H2 antagonists. The mechanism for most cimetidine drug interactions is inhibition of hepatic metabolism. There is conflicting evidence regarding significance of altered liver blood flow for both cimetidine and ranitidine and their influence on other agents. Cimetidine may increase propranolol's blood concentrations and potentiate beta blocking effects through inhibition of hepatic microsomal enzymes and possibly through reduction of hepatic blood flow. Ranitidine has no effect on propranolol. Cimetidine, when administered concurrently with metoprolol, could possibly cause an increase in plasma metoprolol concentrations or bioavailability through inhibition of hepatic P-450 metabolizing enzymes. No effect of cimetidine on metoprolol pharmacodynamics was evident. Ranitidine has no effect on metoprolol pharmacokinetics or pharmacodynamics. Neither H2 antagonist altered the kinetics or physiologic effects of atenolol. Atenolol is the drug of choice in patients receiving H2 antagonists, since no interaction has been observed. Metoprolol could probably be used safely in most patients, as no change in pharmacodynamics has been evident. Concurrent administration of cimetidine and nifedipine may result in alterations in heart rate and blood pressure. The mechanism is inhibition of oxidative liver metabolism. Ranitidine has no effect on nifedipine. Studies are needed to investigate the interaction between the H2 antagonists and diltiazem or verapamil. Cimetidine, given concomitantly with lidocaine, may increase lidocaine concentrations and clinical symptoms of lidocaine toxicity. The mechanism involved is probably a reduction in oxidative drug metabolism or liver blood flow. Ranitidine has no significant effects on lidocaine pharmacokinetics. Cimetidine may increase quinidine levels and symptoms of quinidine toxicity. Additionally, enhanced arrhythmic effects may be observed. The interaction probably caused by an inhibition of hepatic drug metabolism of quinidine by cimetidine would be most significant in patients with liver disease and in the elderly. Ranitidine may enhance quinidine's arrhythmic effect. Cimetidine can possibly increase procainamide and NAPA serum concentrations, especially in the elderly and in patients with renal dysfunction, predisposing them to adverse side effects. The interaction is mediated by a reduction of tubular secretion of procainamide and NAPA.
H2拮抗剂与心血管药物之间的药物相互作用汇总见表I。西咪替丁的效力、亲脂性以及与P-450细胞色素系统的结合亲和力，可能是已确定的与H2拮抗剂发生药物相互作用的原因。大多数西咪替丁药物相互作用的机制是抑制肝代谢。关于西咪替丁和雷尼替丁肝血流改变的意义及其对其他药物的影响，存在相互矛盾的证据。西咪替丁可能通过抑制肝微粒体酶并可能通过减少肝血流来增加普萘洛尔的血药浓度并增强β受体阻滞作用。雷尼替丁对普萘洛尔无影响。西咪替丁与美托洛尔同时给药时，可能通过抑制肝P-450代谢酶导致血浆美托洛尔浓度或生物利用度增加。西咪替丁对美托洛尔药效学无明显影响。雷尼替丁对美托洛尔的药代动力学或药效学无影响。两种H2拮抗剂均未改变阿替洛尔的动力学或生理效应。阿替洛尔是接受H2拮抗剂患者的首选药物，因为未观察到相互作用。美托洛尔在大多数患者中可能可以安全使用，因为药效学没有明显变化。西咪替丁与硝苯地平同时给药可能导致心率和血压改变。机制是抑制肝脏氧化代谢。雷尼替丁对硝苯地平无影响。需要开展研究来调查H2拮抗剂与地尔硫䓬或维拉帕米之间的相互作用。西咪替丁与利多卡因同时给药时，可能会增加利多卡因浓度以及利多卡因毒性的临床症状。涉及的机制可能是氧化药物代谢或肝血流减少。雷尼替丁对利多卡因药代动力学无显著影响。西咪替丁可能会增加奎尼丁水平以及奎尼丁毒性症状。此外，可能会观察到心律失常作用增强。这种相互作用可能是由西咪替丁抑制奎尼丁的肝药物代谢引起的，在肝病患者和老年人中最为显著。雷尼替丁可能会增强奎尼丁的心律失常作用。西咪替丁可能会增加普鲁卡因胺和NAPA的血清浓度，尤其是在老年人和肾功能不全患者中，使他们易出现不良反应。这种相互作用是由普鲁卡因胺和NAPA的肾小管分泌减少介导的。
