Turner Dan, Lurie Yael, Finkelstein Yoram, Schmid Tal, Gopher Asher, Kleid David, Bentur Yedidia
Department of Pediatrics, Shaare Zedek Medical Center, Jerusalem, Israel.
Pediatrics. 2006 May;117(5):e1067-9. doi: 10.1542/peds.2005-2059. Epub 2006 Apr 24.
Cinnarizine, a piperazine derivative, is a widely prescribed medication for the treatment of vestibular disorders and motion sickness. Cinnarizine has antihistaminic, antiserotoninergic, antidopaminergic, and calcium channel-blocking properties. We present the first report in the English literature of cinnarizine poisoning and toxicokinetics. A 30-month-old toddler ingested 225 mg of cinnarizine, 18 times the recommended dose for older children. Four hours later, she became jittery with a wide-based gait and vomited 3 times. She was examined by her family physician, who reported stupor and twitching in both hands. On admission to the hospital, 6 hours after the ingestion, she was stuporous and had 3 short, generalized tonic-clonic convulsions that were controlled with a single dose of midazolam. Full clinical recovery was seen 10 hours after ingestion. Serum cinnarizine levels were 7407, 2629, and 711 ng/mL on admission and at 4 and 12 hours thereafter, respectively, 26.9 times higher than the therapeutic levels in adults. Elimination rate constant, calculated by linear regression of the ln concentrations of the 3 data points, was 0.19. Half-life, calculated from the equation t(1/2) = 0.693/kel, where kel is the elimination rate constant, was 3.65 hours. The manufacturing company revealed that their database contains 23 reports of cinnarizine overdose (adult and children), received between 1972 and 2004. Clinically, these cases reflect mainly symptoms of alterations in consciousness ranging from somnolence to stupor and coma, vomiting, extrapyramidal symptoms, and hypotonia. In a small number of young children, convulsions developed; recovery was uneventful in 4 cases and not reported in 1. The neurologic complication may be explained by the antihistaminic effect of cinnarizine because central nervous system depression and convulsions are known complications of antihistaminic overdose. It is hypothesized that cinnarizine-induced convulsions also are related to the antidopaminergic effect of the drug. Apart from the convulsions, no other adverse effects related to calcium channel-blocking properties, such as bradycardia or hemodynamic instability, were observed. Pediatric patients with cinnarizine overdose need to be observed in a health care facility for potential neurologic complications and be treated symptomatically. The delay to onset of clinical effect should be considered in the observation period.
桂利嗪是一种哌嗪衍生物，是一种广泛用于治疗前庭疾病和晕动病的药物。桂利嗪具有抗组胺、抗血清素、抗多巴胺能和钙通道阻滞特性。我们发表了英文文献中关于桂利嗪中毒及毒物动力学的首例报告。一名30个月大的幼儿摄入了225毫克桂利嗪，是大龄儿童推荐剂量的18倍。4小时后，她变得烦躁不安，步态宽基，呕吐3次。她的家庭医生对其进行了检查，报告称其嗜睡且双手抽搐。摄入后6小时入院时，她处于昏迷状态，发生了3次短暂的全身性强直阵挛性惊厥，单次剂量的咪达唑仑控制住了惊厥。摄入后10小时完全康复。入院时及此后4小时和12小时的血清桂利嗪水平分别为7407、2629和711纳克/毫升，比成人治疗水平高26.9倍。通过对3个数据点的自然对数浓度进行线性回归计算得出的消除速率常数为0.19。根据公式t(1/2)=0.693/kel（其中kel为消除速率常数）计算得出的半衰期为3.65小时。生产公司透露，他们的数据库包含1972年至2004年间收到的23例桂利嗪过量（成人和儿童）报告。临床上，这些病例主要表现为意识改变的症状，从嗜睡到昏迷、呕吐、锥体外系症状和肌张力减退。少数幼儿出现惊厥；4例康复顺利，1例未报告康复情况。神经并发症可能是由桂利嗪的抗组胺作用引起的，因为中枢神经系统抑制和惊厥是抗组胺药过量的已知并发症。据推测，桂利嗪引起的惊厥也与该药物的抗多巴胺能作用有关。除惊厥外，未观察到与钙通道阻滞特性相关的其他不良反应，如心动过缓或血流动力学不稳定。桂利嗪过量的儿科患者需要在医疗机构观察是否有潜在的神经并发症，并进行对症治疗。在观察期应考虑临床效应出现的延迟。
