Interaction of H2-receptor antagonists and benzodiazepine sedation

doi:10.1111/j.1365-2044.1993.tb06944.x

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Wiley InterScience

Anaesthesia

Volume 48 Issue 4, Pages 286 - 292

Published Online: 22 Feb 2007

Journal of the Association of Anaesthetists of Great Britain and Ireland

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Interaction of H₂-receptor antagonists and benzodiazepine sedation

A double-blind placebo-controlled investigation of the effects of cimetidine and ranitidine on recovery after intravenous midazolam

L. D. SANDERS ¹ , C. WHITEHEAD ² , C. D. GILDERSLEVE ³ , M. ROSEN ⁴ J. O. ROBINSON ⁵

¹ L.D. Sanders, PhD, Research Fellow, Department of Anaesthetics, University of Wales, College of Medicine ² C. Whitehead, BA, Research Assistant, Department of Anaesthetics, University of Wales, College of Medicine ³ C.D. Gilidersleve, FRCA, Research Officer, Department of Anaesthetics, University of Wales, College of Medicine ⁴ M. Rosen, CBE, FFARCS, Professor in Anaesthetics, Department of Anaesthetics, University of Wales, College of Medicine ⁵ Cardiff, J.O. Senior Lecturer, School of Psychology, University of Wales College of Cardiff

KEYWORDS

Histamine • cimetidine • ranitidine • Recovery • psychometric tests • Hypnotics • benzodiazepines • midazolam

ABSTRACT

H₂-receptor antagonists differentially inhibit cytochrome P450 and this may affect the rate at which benzodiazepines are metabolised. However, it is not known whether this delayed clearance results in prolonged psychomotor impairment. In a randomised double-blind trial 28 healthy volunteers received two single doses of midazolam (0.07 mg.kg⁻¹) at an interval of one week during which they took cimetidine 400 mg, ranitidine 150 mg or placebo, each twice daily. Recovery from the benzodiazepine was monitored on each occasion over a 12 h period using a battery of psychometric tests. There was wide individual variation in performance; however, an overall measure of impairment indicated a significant difference at 2.5 h (p < 0.05), the cimetidine group having a high impairment score. This decrement appeared to be in cognitive and psychomotor functions and was not reflected in the subjective assessment.

Accepted 20 September 1992

DIGITAL OBJECT IDENTIFIER (DOI)

10.1111/j.1365-2044.1993.tb06944.x About DOI