Orphenadrine poisoning in a child: clinical and analytical data

Abstract

Orphenadrine is an anticholinergic drug used mainly in the treatment of Parkinson's disease. It has a peripheral and central effect and a known cardiotoxic effect when taken in large doses. We report the successful outcome of the treatment of a 2 1/2-year-old girl who accidentally ingested 400 mg of orphenadrine hydrochloride (Disipal). One hour after ingestion she presented neurological symptoms: confusion, ataxic walking, and periods of severe agitation. Generalized tonic-clonic seizures appeared resistant to the administration of multiple antiepileptics. They ceased after a supplementary dose of intravenous diazepam, endotracheal intubation, and mechanical ventilation. An episode of ventricular tachycardia responded well to i. v. lidocaine. Physostigmine was administered in three successive doses. The initial orphenadrine plasma level (3,55 microg/ml) was in the toxic range, associated with high mortality. The calculated elimination half-life was 10.2 h and the molecule and/or its metabolites were found up to 90 h after ingestion.

Prolonged Antimuscarinic Delirium in a Child Due to Benztropine Exposure Treated With Multiple Doses of Physostigmine

“…7,8 Although rare, its use in the pediatric population has been reported for toxicity from diphenhydramine, orphenadrine, and antimuscarinic plants. [21][22][23] There are no prior reports using it for pediatric benztropine poisoning. In our patient, 1.5 mg of physostigmine rapidly and completely reversed his delirium.…”

Pharmacokinetic study of orphenadrine using high-performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS)

“…Blood concentrations >500 ng/mL may cause toxic reactions and >5000 ng/mL may be lethal [3]. Accidental intoxication in children and a few cases of death have resulted from overdose of orphenadrine in schizophrenic patients [2][3][4]. Therefore, determination of blood orphenadrine levels and improved understanding of its pharmacokinetics may be help assess poisoned patients as well as improve monitoring in patients on the chronic therapy where indicated.…”

“…There is also reported cases of orphenadrine poisoning [2][3][4]. Blood concentrations of orphenadrine greater than 500 ng/mL may cause toxic reactions.…”

“…Determination of blood orphenadrine levels and understanding of its pharmacokinetics may be helpful in assessing poisoning in patients as well as monitoring of patients on chronic therapy. To date, the orphenadrine measurements on plasma samples have been performed either by HPLC-UV [2,6], GC [7] or GC/MS [3], all labor-intensive and time-consuming methods. The purpose of this study was to develop simple and reliable HPLC-MS/MS method for determination of plasma orphenadrine, to apply this technique to bioavailability studies, and to examine pharmacokinetic parameters of orphenadrine in 24 healthy subjects.…”

Torsades de pointes in congenital long qt syndrome following low-dose orphenadrine

“…It is, therefore, conceivable that, in patients with LQTS, orphenadrine can decrease the ‘repolarisation reserve’ (7), thereby enhancing the risk of the life‐threatening arrhythmias. Previous papers have pointed out the risk of cardiotoxicity, and especially of dangerous ventricular arrhythmias, after orphenadrine assumption (8–10). To the best of our knowledge, there is just one case of ventricular arrhythmias induced by low‐dose orphenadrine; in that case, there was neither QT prolongation nor hypokaliemia, and the authors hypothesised that the combination of the drug with a sodium channel‐blocking agent (propafenone) was probably responsible for the ventricular tachycardia (10).…”