Diminished sedation during diazepam treatment for chloroquine intoxication
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We report a case of a woman hospitalized after chloroquine overdose whose whole blood concentration on admission was 7.87Μg/ml. High blood concentrations of chloroquine induce cardiotoxicity and have been associated with death when they exceed 3.0Μg/ml. Early administration of massive doses of diazepam has been described to reduce the mortality due to chloroquine toxicity, but the protective mechanism has remained unknown. This patient was treated with diazepam (2.0 mg/kg over 30 min followed by a dosage of 1.0 to 2.0 mg/kg over 24 h), yet she remained awake despite the high plasma concentrations of diazepam and nordiazepam which would normally be associated with sedation. This suggests an antagonistic effect of chloroquine on the benzodiazepine-induced sedation due to an interaction between these drugs at their site of action.
KeywordsChloroquine Diazepam Drug interactions Poisoning
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- 1.Titus EO. Recent developments in the understanding of the pharmacokinetics and mechanism of action of chloroquine. Ther Drug Monitor 1989;11:369–79.Google Scholar
- 2.Riou B, Barriot P, Rimailho A, Baud FJ. Treatment of severe chloroquine poisoning. N Engl J Med 1988;318:1–6.Google Scholar
- 3.Ette EI, Essien EE, Thomas WOA, Brown-Awala EA. Pharmaco-kinetics of chloroquine and some of its metabolites in healthy volunteers: a single dose study. J Clin Pharmacol 1989;29:457–62.Google Scholar
- 4.Augustijns P, Verbeke N. HPLC method for the determination of chloroquine and its main metabolite in biological samples. J Liq Chromatogr 1990;13(6):1203–13.Google Scholar
- 5.Rutherford DM. Rapid micro-method for the measurement of diazepam and desmethyldiazepam in blood plasma by gas-liquid chromatography. J Chromatogr 1977;137:439–48.Google Scholar
- 6.Augustijns P. A study of the pharmacokinetic properties of chloroquine and its enantiomers [dissertation]. Leuven: Catholic University Leuven, 1991.Google Scholar
- 7.Ellenhorn MJ, Barceloux DG. Medical toxicology. New York: Elsevier Science Publishing Company, 1988:342–4.Google Scholar
- 8.Stead AH, Moffat AC. A collection of therapeutic, toxic and fatal blood drug concentrations in man. Human Toxicol 1983;3:437–64.Google Scholar
- 9.Liu L, Katz Y, Weizman R, Rosenberg B, Pasternak GW, Gavish M. Interactions of chloroquine with benzodiazepine, gamma-aminobutyric acid and opiate receptors. Biochem Pharmacol 1991;41:1534–6.Google Scholar
- 10.Nogrady T. Medicinal chemistry. 2nd ed. New York: Oxford University Press, 1988:225–39.Google Scholar