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Ciprofloxacin Cardiotoxicity and Hepatotoxicity in Humans and Animals

机译:环丙沙星对人和动物的心脏毒性和肝毒性

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Ciprofloxacin is generally well tolerated; the most common adverse effects include gastro intestinal tract, central nervous system and hematological system effects. Recently rising cases of Ciprofloxacin associated toxicity have been reported. Experiment using animal models and clinical experience showed that Ciprofloxacin induced cardiotoxicity is marked by increase QT and QTC interval and prolonged action potential duration. This increases the risk of arrhythmia (tosarde de pointes). Ciprofloxacin induced cardiotoxic effect could be associated with blocking cardiac voltage—gated potassium channels particularly the rapid component (IKr) of the delayed rectifier potassium current. Drug interaction with inhibitors of Cytochrome P450 (CYP) mediated metabolism could be one of the underlying mechanisms. Several cases of Ciprofloxacin induced hepatoxicity have been also reported. These were characterized by extensive hepatocellular necrosis, mixed inflammatory infiltrate and abundant esinophils in the liver. Elevated liver enzymes which include serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gramma-glutamyltranferase and prolong prothrobin time were reported. The hepatotoxic effect of Ciprofloxacin as reported could be due to oxidative stress induced in the liver by Ciprofloxacin through the generation of oxidative radicals leading to depletion of protein content in hepatocytes as a consequence of nucleic acids diminution and DNA damage. This may lead to significant decrease in the number and degeneration in mitochondria which is responsible for energy supply. Conclusion: Ciprofloxacin induced cardiotoxicity and hepatotoxicity is relatively low in humans but patients’ liver and cardiac function may be considered before Ciprofloxacin use.
机译:环丙沙星一般耐受良好;最常见的不良反应包括胃肠道,中枢神经系统和血液系统的影响。最近报道了环丙沙星相关毒性上升的病例。使用动物模型进行的实验和临床经验表明,环丙沙星诱导的心脏毒性以QT和QTC间隔的增加以及动作电位持续时间的延长为特征。这增加了心律不齐的风险(tosarde de pointes)。环丙沙星诱导的心脏毒性作用可能与阻断心脏电压有关-门控钾通道,特别是延迟整流钾电流的快速成分(IKr)。与细胞色素P450(CYP)介导的代谢抑制剂的药物相互作用可能是其潜在机制之一。还报道了环丙沙星诱导的肝毒性的几例。这些特征是肝中广泛的肝细胞坏死,混合的炎性浸润和丰富的嗜酸性粒细胞。据报道,肝脏酶升高,包括血清天冬氨酸转氨酶,丙氨酸转氨酶,碱性磷酸酶和γ-谷氨酰转移酶,并延长了原色蛋白的时间。如所报道的环丙沙星的肝毒性作用可能是由于环丙沙星通过氧化自由基的产生在肝脏中诱导的氧化应激,该氧化自由基导致了核酸的减少和DNA损伤而导致肝细胞中蛋白质含量的减少。这可能导致负责能量供应的线粒体数量减少和退化。结论:环丙沙星对人的心脏毒性和肝毒性相对较低,但在使用环丙沙星前应考虑患者的肝和心功能。

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