Saini R K, Fulmor I E, Antonaccio M J
J Cardiovasc Pharmacol. 1982 Sep-Oct;4(5):770-6. doi: 10.1097/00005344-198209000-00012.
The hemodynamic effects exerted by two chemically dissimilar calcium antagonists (tiapamil and nifedipine) were studied in anesthetized dogs during control conditions, following critical stenosis of the left circumflex coronary artery, and in the presence of beta-receptor blockade with nadolol (1 mg/kg). Dose-dependent hemodynamic changes were observed following the intravenous administration of three different doses of tiapamil (0.5, 1.0, and 2.0 mg/kg) and nifedipine (2.5, 5.0, and 10.0 micrograms/kg) during control conditions. In the presence of critical coronary stenosis, tiapamil and nifedipine produced similar magnitudes of decreases in blood pressure and changes in heart rate. Tiapamil produced paradoxic increases in left ventricular (LV) dP/dt and contractile force since these changes were accompanied by a slight decrease in heart rate. Nifedipine, unlike tiapamil, resulted in reflex increases in heart rate and myocardial contractility in response to reduction in the afterload. Also, nifedipine, unlike tiapamil, produced relatively minor changes in the coronary flow of the unoccluded left anterior descending coronary artery. In the presence of nadolol and critical stenosis, both agents produced markedly different hemodynamic responses. In the tiapamil series, three out of five dogs died due to severe cardiodepression consisting of bradycardia, hypotension, reduced myocardial contractility, and coronary blood flow. No mortality was observed in the nifedipine series since the cardiac function was adequately maintained in the presence of beta-blockade. Our results are in close agreement with the clinical observations, indicating a much higher incidence of dangerous drug interactions with combined use of verapamil-like compounds (e.g., tiapamil) with beta-blockers than with nifedipine, especially in patients with coronary artery disease and AV conduction disturbances.
在麻醉犬身上，研究了两种化学性质不同的钙拮抗剂（硫氮䓬酮和硝苯地平）在对照状态下、左旋冠状动脉严重狭窄后以及存在纳多洛尔（1毫克/千克）β受体阻滞时的血流动力学效应。在对照状态下，静脉注射三种不同剂量的硫氮䓬酮（0.5、1.0和2.0毫克/千克）和硝苯地平（2.5、5.0和10.0微克/千克）后，观察到剂量依赖性的血流动力学变化。在存在严重冠状动脉狭窄时，硫氮䓬酮和硝苯地平使血压下降幅度相似，心率变化也相似。硫氮䓬酮使左心室（LV）dP/dt和收缩力出现反常增加，因为这些变化伴随着心率略有下降。与硫氮䓬酮不同，硝苯地平因后负荷降低导致心率和心肌收缩力反射性增加。此外，与硫氮䓬酮不同，硝苯地平对未闭塞的左前降支冠状动脉血流产生的变化相对较小。在存在纳多洛尔和严重狭窄时，两种药物产生了明显不同的血流动力学反应。在硫氮䓬酮组中，五只犬中有三只死于严重的心脏抑制，包括心动过缓、低血压、心肌收缩力降低和冠状动脉血流减少。硝苯地平组未观察到死亡情况，因为在β受体阻滞存在的情况下心脏功能得到了充分维持。我们的结果与临床观察结果密切一致，表明与硝苯地平相比，维拉帕米类化合物（如硫氮䓬酮）与β受体阻滞剂联合使用时发生危险药物相互作用的发生率要高得多，尤其是在患有冠状动脉疾病和房室传导障碍的患者中。
