Literature DB >> 21228393

Myoclonus after dextromethorphan administration in peritoneal dialysis.

Akio Tanaka1, Tadashi Nagamatsu, Makoto Yamaguchi, Atsushi Nomura, Fumiko Nagura, Kayaho Maeda, Tatsuhito Tomino, Tatsuhito Watanabe, Hideaki Shimizu, Yoshiro Fujita, Yasuhiko Ito.   

Abstract

OBJECTIVE: To report a case of myoclonus that developed after administration of dextromethorphan. CASE
SUMMARY: A 64-year-old man was diagnosed with chronic renal failure due to diabetic nephropathy. The patient started on peritoneal dialysis 6 months before he was hospitalized. Two days before hospitalization, he developed cough and sputum and he visited an outpatient clinic, where dextromethorphan was prescribed. After taking a total of 30 mg of dextromethorphan, the patient developed myoclonus, tremor, agitation, slurred speech, and diaphoresis, which continued after he stopped taking the prescribed medicine. He visited an emergency department and was hospitalized for examination and treatment of myoclonus. DISCUSSION: As the patient's dialysis schedule was adequate, these symptoms were likely not due to uremia. The blood concentration of dextromethorphan (2.68 ng/mL) 60 hours after the 30-mg dose was higher than expected, and the blood concentration of dextrorphan, a metabolite, was lower than expected. We suspected that myoclonus was due to dextromethorphan-related symptoms induced by CYP2D6, which primarily metabolizes dextromethorphan. We analyzed the CYP2D6 gene for polymorphisms and identified CYP2D6 (*)1/(*)10. The patient had been taking metoprolol 40 mg/day for 2 years. The blood concentration of metoprolol 6 hours after administration was 13 ng/mL, which suggests that it was metabolized normally. Metoprolol has another metabolic pathway, via CYP2C19, and this may have led to its lack of accumulation. Moreover, metoprolol may have bound to active CYP2D6. Thus, affinity for CYP2D6, protein-binding rate, and lipid solubility may influence these drug interactions. Total scores for the Adverse Drug Reaction (ADR) probability scale and the Drug Interaction Probability Scale (DIPS) were 9 (highly probable) and 3 (possible), respectively.
CONCLUSIONS: Myoclonus and other symptoms in this patient may have been caused by a prolonged high concentration of dextromethorphan due to CYP2D6 polymorphisms and drug interactions.

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Year:  2010        PMID: 21228393     DOI: 10.1345/aph.1P301

Source DB:  PubMed          Journal:  Ann Pharmacother        ISSN: 1060-0280            Impact factor:   3.154


  4 in total

Review 1.  Complex Drug-Drug-Gene-Disease Interactions Involving Cytochromes P450: Systematic Review of Published Case Reports and Clinical Perspectives.

Authors:  Flavia Storelli; Caroline Samer; Jean-Luc Reny; Jules Desmeules; Youssef Daali
Journal:  Clin Pharmacokinet       Date:  2018-10       Impact factor: 6.447

2.  PKCδ Knockout Mice Are Protected from Dextromethorphan-Induced Serotonergic Behaviors in Mice: Involvements of Downregulation of 5-HT1A Receptor and Upregulation of Nrf2-Dependent GSH Synthesis.

Authors:  Hai-Quyen Tran; Youngho Lee; Eun-Joo Shin; Choon-Gon Jang; Ji Hoon Jeong; Akihiro Mouri; Kuniaki Saito; Toshitaka Nabeshima; Hyoung-Chun Kim
Journal:  Mol Neurobiol       Date:  2018-02-22       Impact factor: 5.590

Review 3.  The clinical heterogeneity of drug-induced myoclonus: an illustrated review.

Authors:  Sabine Janssen; Bastiaan R Bloem; Bart P van de Warrenburg
Journal:  J Neurol       Date:  2016-12-16       Impact factor: 4.849

4.  Two cases of mild serotonin toxicity via 5-hydroxytryptamine 1A receptor stimulation.

Authors:  Hiroto Nakayama; Sumiyo Umeda; Masashi Nibuya; Takeshi Terao; Koichi Nisijima; Soichiro Nomura
Journal:  Neuropsychiatr Dis Treat       Date:  2014-02-11       Impact factor: 2.570

  4 in total

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