Infection and Inflammation Leading to Clozapine Toxicity and Intensive Care: A Case Series
Infection and Inflammation Leading to Clozapine Toxicity and Intensive Care: A Case Series
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DOI：
10.1177/1060028014526701
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发表时间：
2014-06-01
影响因子：
2.9
通讯作者：
Goeren, Jessica L.
中科院分区：
文献类型：
--
作者：
Leung, Jonathan G.;Nelson, Sarah;Goeren, Jessica L.
目的：描述3例氯氮平毒性与感染和/或炎症过程相关的病例。病例总结：三名患者在入院前稳定的氯氮平治疗后出现氯氮平毒性。怀疑每位患者的急性感染和/或炎症过程与突然的精神状态改变、唾液、肌阵挛发作和/或需要呼吸支持有关。精神状态改变的调查未发现其他原因，表现与抗精神病药恶性综合征、其他急性神经系统并发症或精神代偿失调不一致。所有患者在减少氯氮平剂量后均得到改善，允许从重症监护病房转移。对每个病例使用Naranjo不良反应概率量表，确定氯氮平毒性与感染和/或炎症过程之间的可能关系。讨论：氯氮平毒性可表现为多种症状，包括镇静、唾液分泌和低血压。除了过量和药物相互作用；感染和/或炎症可引起氯氮平毒性。这可能与细胞因子介导的细胞色素P450 1A2抑制有关。通过这种机制产生毒性的可能性尚未得到很好的描述，因此对接受氯氮平治疗的内科病人需要仔细监测。氯氮平与急性期反应物α -1酸性糖蛋白广泛结合，这可能会不可预知地防止临床毒性。c反应蛋白也被研究氯氮平毒性与感染和/或炎症的关系。结论：氯氮平毒性发生在3例被怀疑与感染和/或炎症有关的医疗机构。临床医生应该意识到氯氮平的潜在不良事件。
Objective: To describe 3 cases of clozapine toxicity associated with infectious and/or inflammatory processes. Case Summaries: Three patients stable on clozapine therapy prior to a medical hospital admission developed clozapine toxicity. It was suspected that an acute infectious and/or inflammatory process in each patient was related to abrupt mental status changes, onset of sialorrhea, myoclonus, and/or need for ventilatory support. Investigations of altered mental status did not reveal alternative causes and presentations were not consistent with neuroleptic malignant syndrome, other acute neurologic complications, or psychiatric decompensation. All patients improved after clozapine dose reductions allowing for transfer from intensive care units. Using the Naranjo ADR Probability Scale for each case, a probable relation between clozapine toxicity and the infectious and/or inflammatory process was determined. Discussion: Clozapine toxicity may manifest with multiple symptoms, including sedation, sialorrhea, and hypotension. In addition to overdose and drug interactions; infection and/or inflammation may precipitate clozapine toxicity. This may be related to cytokine-mediated inhibition of cytochrome P450 1A2. The likelihood of toxicity via this mechanism has not been well characterized, thus careful monitoring is required for medically ill patients receiving clozapine. Clozapine is extensively bound to the acute phase reactant, alpha-1 acid glycoprotein, which may unpredictably protect against clinical toxicity. C-reactive protein has also been investigated to relate clozapine toxicity to infection and/or inflammation. Conclusion: Clozapine toxicity developed in 3 patients admitted to a medical setting suspected to be related to infection and/or inflammation. Clinicians should be aware of this potential adverse drug event with clozapine.