Faculty of Medicine, University of New South Wales, Sydney, Australia.
Faculty of Medicine and Health, University of Sydney, Sydney, Australia.
Clin Toxicol (Phila). 2021 Jun;59(6):464-471. doi: 10.1080/15563650.2020.1826504. Epub 2020 Oct 6.
Amlodipine, a dihydropyridine calcium channel blocker (CCB), is the leading cause of cardiovascular drug-related overdose deaths in the USA. In contrast, angiotensin-II receptor blockers (ARBs) and angiotensin converting enzyme inhibitors (ACEIs) cause minimal toxicity in overdose. ACEIs/ARBs are often combined with dihydropyridines in hypertension treatment. Co-ingested ARBs/ACEIs may significantly contribute to the toxicity of dihydropyridine, but this has not been investigated.
To investigate the clinical outcomes from dihydropyridine overdoses with ARBs/ACEIs versus dihydropyridine overdoses alone.
This was a retrospective study of patients reported to the New South Wales Poisons Information Centre (NSW PIC) and 3 toxicology units (Jan 2016 to Jun 2019) in Australia. Patients >14 years who took an overdose of dihydropyridines (amlodipine, felodipine, lercanidipine, nifedipine) were included. Concurrent overdoses with non-dihydropyridine CCBs, alpha-blockers and beta-blockers were excluded. Patient demographics, drugs exposure details, serial vital signs, treatments and outcome were collected.
There were 100 patients. 68 took mixed overdoses of dihydropyridines with ARBs/ACEIs and 32 took single overdoses of dihydropyridines without ARBs/ACEIs. The mixed group had lower median nadir mean arterial pressures (62 vs 75 mmHg, < 0.001), more frequently had hypotension (OR 4.5, 95%CI: 1.7-11.9) or bradycardia (OR 8.8, 95%CI: 1.1-70). Multivariable analysis indicated the mixed overdoses had an 11.5 mmHg (95%CI: 4.9-18.1) lower minimum systolic blood pressure (SBP) compared with the single group; other factors associated with a lower minimum SBP were higher doses [2.3 mmHg (95%CI: 1.1-3.5) lower per 10 defined daily doses] and younger age [2.2 mmHg (95%CI: 0.3-4.2) higher per decade]. A larger proportion of the mixed ingestion group received intravenous fluids (OR 5.7, 95%CI: 1.8-18.6) and antidotes and/or vasopressors (OR 2.9, 95%CI: 1.004-8.6).
Combined overdoses of dihydropyridines with ARBs/ACEIs caused more significant hypotension and required more haemodynamic support than overdoses of dihydropyridines alone.
氨氯地平，一种二氢吡啶钙通道阻滞剂（CCB），是导致美国心血管药物相关过量死亡的主要原因。相比之下，血管紧张素-II 受体阻滞剂（ARB）和血管紧张素转换酶抑制剂（ACEI）在过量服用时毒性最小。ACEI/ARB 通常与二氢吡啶类药物联合用于高血压治疗。同时摄入 ARB/ACEI 可能会显著增加二氢吡啶类药物的毒性，但这尚未得到研究。
研究同时服用 ARB/ACEI 和单独服用二氢吡啶类药物的二氢吡啶类药物过量患者的临床结局。
这是一项对澳大利亚新南威尔士毒物信息中心（NSW PIC）和 3 个毒理学单位（2016 年 1 月至 2019 年 6 月）报告的患者进行的回顾性研究。纳入年龄>14 岁、服用二氢吡啶类药物（氨氯地平、非洛地平、乐卡地平、硝苯地平）过量的患者。排除同时服用非二氢吡啶类 CCB、α-受体阻滞剂和β-受体阻滞剂的患者。收集患者的人口统计学、药物暴露详细信息、连续生命体征、治疗和结局。
共纳入 100 例患者。68 例患者同时服用二氢吡啶类药物与 ARB/ACEI，32 例患者单独服用二氢吡啶类药物而未服用 ARB/ACEI。混合组的中位数最低平均动脉压更低（62 对 75mmHg，<0.001），更频繁地出现低血压（OR 4.5，95%CI：1.7-11.9）或心动过缓（OR 8.8，95%CI：1.1-70）。多变量分析表明，与单独组相比，混合组的最低收缩压（SBP）低 11.5mmHg（95%CI：4.9-18.1）；与最低 SBP 较低相关的其他因素包括较高剂量[每 10 个定义日剂量低 2.3mmHg（95%CI：1.1-3.5）]和年龄较小[每 10 年高 2.2mmHg（95%CI：0.3-4.2）]。混合摄入组接受静脉补液（OR 5.7，95%CI：1.8-18.6）和解毒剂和/或血管加压药的比例更高（OR 2.9，95%CI：1.004-8.6）。
与单独服用二氢吡啶类药物相比，同时服用二氢吡啶类药物与 ARB/ACEI 会导致更严重的低血压，并需要更多的血流动力学支持。
