Chloroquine-Induced Acute Dystonic Reactions in the Presence of Metronidazole

Abstract

A 30-year-old woman underwent laparotomy and was placed on a seven-day course of metronidazole and ampicillin postoperatively. Chloroquine therapy for malaria was instituted on the sixth day and the patient developed acute dystonic reactions after a single dose. Diphenhydramine therapy before chloroquine administration did not prevent the development of the dystonic reactions. The extrapyramidal symptoms subsided upon diazepam administration and chloroquine withdrawal even though metronidazole therapy was continued. The mechanism of this adverse drug reaction based on the pharmacodynamic interaction between chloroquine and metronidazole is discussed. It is suggested that the combination of pyrimethamine and sulfadoxine be used in place of chloroquine for malaria chemotherapy in patients on metronidazole therapy.

Chloroquine Induced Acute Dystonic Reactions after a Standard Therapeutic Dose for Uncomplicated Malaria = تفاعل خلل التوتر العضلي الحاد بعد جرعة قياسية للكلوروكين لعلاج الملاريا غير المعقدة

“…However, it has been linked to a reduction in forebrain catecholamine levels and an inhibition of neuronal calcium uptake. 19 This hypothesis could be supported in part by the effectiveness of benzodiazepines in the reversal of CQ-associated ADR. A normal balance between dopamine and acetylcholine in the basal ganglia involves modulation from gamma aminobutyric acid (GABA)-containing striatonigral neurons.…”

“…18 Achumba et al reported a case of ADR after a single dose of CQ in a postoperative patient and in the presence of metronidazole. 19 The reported case suggested that the ADR might have been an idiosyncratic reaction and probably potentiated by the metronidazole. In our case, the ADR also occurred after a single dose of CQ but in the absence of any other medications.…”

“…Although ADRs occasionally are dose-related, they are more often idiosyncratic and unpredictable. 19 For most drugs that often cause ADR, particularly the neuroleptics, the pathophysiology is a drug-induced alteration of dopaminergiccholinergic balance in the nigrostriatum. They produce ADR by a nigrostriatal dopamine D2 receptor blockade, which results in an excess of striatal cholinergic output.…”

Amodiaquine-associated adverse effects after inadvertent overdose and after a standard therapeutic dose

“…13 This assertion could be supported in part, by the observed effectiveness and symptom reversal of the dystonia by diazepam: it has been proposed that stimulation of the benzodiazepine receptors coupled to the γ-amino butyric acid (GABA) receptors via the chloride ion channel in the central nervous system facilitate GABA transmission, with a consequent inhibitory effect on muscle hypertonia and tremors. Other possible mechanisms that may underlie amodiaquine-associated adverse effects could be related to, CYP1A1 or 1B1-mediated extrahepatic metabolism of amodiaquine 3 , or biotransformation to chemically reactive electrophilic quinoneimine metabolites which, by forming immunogenic complexes, may lead to organ-specific toxicity in susceptible individuals.…”

Clinically Significant Drug Interaction Profiles of Chloroquine Analogues with Adverse Consequences and Risk Management

“…The interaction between metronidazole and CQ associated with acute dystonic reactions such as facial grimacing, coarse tremors, and an inability to maintain posture in patient is reported [72].…”