PDF(Pubmed)
Abstract：
BACKGROUND: Dystonia is a known neurological complication of certain medications; however, the mechanism behind such effects is often undetermined. Similarly, the clinical pharmacogenomic effects associated with various alleles of the cytochrome P450 family of proteins, and their role in acute dystonic reactions, are also presently unknown.
METHODS: We describe a woman presenting with acute dystonic reactions to ondansetron, prochlorperazine, and metoclopramide followed by persistent focal dystonia. A similar family history was reported in her siblings and her father to prochlorperazine, drugs all metabolized by the cytochrome P450 2D6 (CYP2D6) enzyme. Pharmacogenomic testing indicated the patient was heterozygous for the intermediate metabolizer *41 allele (CYP2D6 2988G>A, NM_000106.6:c.985+39G>A, rs28371725). Her father was homozygous for this CYP2D6 *41 allele, and consequently, her siblings were obligate carriers.
CONCLUSIONS: The metabolism of ondansetron, metoclopramide, or prochlorperazine in patients with the *41 CYP2D6 allele has not been studied. In this family, clinical evidence implicates the *41 CYP2D6 allele as causing extrapyramidal adverse pharmacologic reactions. Patients with a family history of medication-induced dystonia involving these medications should be considered for pharmacogenomic testing, and patients carrying the *41 CYP2D6 allele should consider reduction or avoidance of CYP2D6-mediated medications to minimize the potential risk of adverse extrapyramidal effects.
METHODS: We describe a woman presenting with acute dystonic reactions to ondansetron, prochlorperazine, and metoclopramide followed by persistent focal dystonia. A similar family history was reported in her siblings and her father to prochlorperazine, drugs all metabolized by the cytochrome P450 2D6 (CYP2D6) enzyme. Pharmacogenomic testing indicated the patient was heterozygous for the intermediate metabolizer *41 allele (CYP2D6 2988G>A, NM_000106.6:c.985+39G>A, rs28371725). Her father was homozygous for this CYP2D6 *41 allele, and consequently, her siblings were obligate carriers.
CONCLUSIONS: The metabolism of ondansetron, metoclopramide, or prochlorperazine in patients with the *41 CYP2D6 allele has not been studied. In this family, clinical evidence implicates the *41 CYP2D6 allele as causing extrapyramidal adverse pharmacologic reactions. Patients with a family history of medication-induced dystonia involving these medications should be considered for pharmacogenomic testing, and patients carrying the *41 CYP2D6 allele should consider reduction or avoidance of CYP2D6-mediated medications to minimize the potential risk of adverse extrapyramidal effects.
摘要：
背景：肌张力障碍是某些药物的已知神经系统并发症；然而，这种影响背后的机制往往是不确定的。同样，与细胞色素P450家族蛋白质的各种等位基因相关的临床药物基因组效应，以及它们在急性肌张力障碍反应中的作用，目前也是未知的。
方法：我们描述了一名女性，对昂丹司琼表现出急性肌张力障碍反应，丙氯哌嗪,和甲氧氯普胺，然后是持续性局灶性肌张力障碍。据报道，她的兄弟姐妹和父亲有类似的家族史，药物均由细胞色素P4502D6（CYP2D6）酶代谢。药物基因组学测试表明该患者的中间代谢*41等位基因是杂合的（CYP2D62988G>A，NM_000106.6：c.985+39G>A，rs28371725)。她的父亲是这个CYP2D6*41等位基因的纯合子，因此，她的兄弟姐妹是义务携带者。
结论：昂丹司琼的代谢，甲氧氯普胺,或丙氯拉嗪在*41CYP2D6等位基因患者中尚未研究。在这个家庭里,临床证据提示*41CYP2D6等位基因可引起锥体外系药物不良反应.有涉及这些药物的药物诱导肌张力障碍家族史的患者应考虑进行药物基因组学测试。携带*41CYP2D6等位基因的患者应考虑减少或避免CYP2D6介导的药物治疗,以将锥体外系不良反应的潜在风险降至最低.
方法：我们描述了一名女性，对昂丹司琼表现出急性肌张力障碍反应，丙氯哌嗪,和甲氧氯普胺，然后是持续性局灶性肌张力障碍。据报道，她的兄弟姐妹和父亲有类似的家族史，药物均由细胞色素P4502D6（CYP2D6）酶代谢。药物基因组学测试表明该患者的中间代谢*41等位基因是杂合的（CYP2D62988G>A，NM_000106.6：c.985+39G>A，rs28371725)。她的父亲是这个CYP2D6*41等位基因的纯合子，因此，她的兄弟姐妹是义务携带者。
结论：昂丹司琼的代谢，甲氧氯普胺,或丙氯拉嗪在*41CYP2D6等位基因患者中尚未研究。在这个家庭里,临床证据提示*41CYP2D6等位基因可引起锥体外系药物不良反应.有涉及这些药物的药物诱导肌张力障碍家族史的患者应考虑进行药物基因组学测试。携带*41CYP2D6等位基因的患者应考虑减少或避免CYP2D6介导的药物治疗,以将锥体外系不良反应的潜在风险降至最低.
