Ginanneschi Federica, Volpi Nila, Giannini Fabio, Rocchi Raffaele, Donati Donatella, Aglianò Margherita, Lorenzoni Paola, Rossi Alessandro
Department of Medical Sciences, Surgical Sciences and Neurosciences, Siena University, 53100 Siena, Italy.
Department of Medical Sciences, Surgical Sciences and Neurosciences, Siena University, 53100 Siena, Italy.
J Neurol Sci. 2014 Jan 15;336(1-2):284-7. doi: 10.1016/j.jns.2013.10.040. Epub 2013 Nov 6.
Rhabdomyolysis precipitated by multitherapy is most frequently described during statin treatment, due to impairment of statin clearance by drugs sharing cytochrome P450 biotransformation pathway. Modulation of membrane transporters for drug efflux, operated by substrates, can also affect drugs' tissue levels. We report rhabdomyolysis in an elderly patient, in multitreatment with different potentially myotoxic medications, taking place seven months after atorvastatin discontinuation. Affected by ischaemic heart disease, arterial hypertension and dementia-related behaviour disturbances, the patient was receiving angiotensin 2-receptor inhibitors, beta-blockers, vasodilators, diuretics, salycilates, allopurinol, proton pump inhibitors, antipsychotics and antidepressants. He had taken atorvastatin for 14 years, with constantly normal creatine-kinase plasma levels. Two months after addition of the antianginal drug ranolazine, creatine-kinase mildly increased and atorvastatin was withdrawn. Nonetheless, creatine-kinase progressively rose, with severe weakness and rhabdomyolysis developing seven months later. Muscle biopsy showed a necrotizing myopathy with no inflammation or autoimmune changes. After ranolazine withdrawal, creatine-kinase and myoglobin returned to normal levels and strength was restored. Several psychotropic and cardiovascular medications prescribed to the patient share either cytochrome P450 biotransformation and permeability-glycoprotein efflux transport. In the event of cardiovascular/neuropsychiatric polypharmacy in geriatric patients, the risk of muscle severe adverse effects from pharmacokinetic drug-drug interaction should be considered beyond the direct myotoxicity of statins.
多药联合治疗引发的横纹肌溶解症在他汀类药物治疗期间最为常见，这是由于共享细胞色素P450生物转化途径的药物会损害他汀类药物的清除。由底物操作的药物外排膜转运体的调节也会影响药物的组织水平。我们报告了一例老年患者的横纹肌溶解症，该患者正在接受多种可能具有肌毒性的药物联合治疗，在停用阿托伐他汀七个月后发生。该患者患有缺血性心脏病、动脉高血压和与痴呆相关的行为障碍，正在接受血管紧张素2受体抑制剂、β受体阻滞剂、血管扩张剂、利尿剂、水杨酸盐、别嘌醇、质子泵抑制剂、抗精神病药物和抗抑郁药物治疗。他服用阿托伐他汀14年，血浆肌酸激酶水平一直正常。在加用抗心绞痛药物雷诺嗪两个月后，肌酸激酶轻度升高，阿托伐他汀停药。尽管如此，肌酸激酶仍逐渐升高，七个月后出现严重无力和横纹肌溶解症。肌肉活检显示为坏死性肌病，无炎症或自身免疫改变。停用雷诺嗪后，肌酸激酶和肌红蛋白恢复到正常水平，肌力恢复。该患者所服用的几种精神药物和心血管药物共享细胞色素P450生物转化和通透性糖蛋白外排转运。在老年患者发生心血管/神经精神科多药联合治疗的情况下，除了他汀类药物的直接肌毒性外，还应考虑药代动力学药物相互作用导致肌肉严重不良反应的风险。
