Hemodynamic Changes by Drug Interaction of Adrenaline With Chlorpromazine
Adrenaline (epinephrine) is included in dental local anesthesia for the purpose of vasoconstriction. In Japan, adrenaline is contraindicated for use in patients receiving antipsychotic therapy, because the combination of adrenaline and an antipsychotic is considered to cause severe hypotension; however, there is insufficient evidence supporting this claim. The purpose of the present study was to clarify the changes in hemodynamics caused by drug interaction between adrenaline and an antipsychotic and to evaluate the safety of the combined use of adrenaline and an antipsychotic in an animal study. Male Sprague-Dawley rats were anesthetized with sodium pentobarbital. A catheter was inserted into the femoral artery to measure blood pressure and pulse rate. Rats were pretreated by intraperitoneal injection of chlorpromazine or chlorpromazine and propranolol, and after 20 minutes, saline or 1 of 3 different doses of adrenaline was administered by intraperitoneal injection. Changes in the ratio of mean arterial blood pressure and pulse rate were measured after the injection of adrenaline. Significant hypotension and tachycardia were observed after the injection of adrenaline in the chlorpromazine-pretreated rats. These effects were in a dose-dependent manner, and 100 μg/kg adrenaline induced significant hemodynamic changes. Furthermore, in the chlorpromazine and propranolol–pretreated rats, modest hypertension was induced by adrenaline, but hypotension and tachycardia were not significantly shown. Hypotension was caused by a drug interaction between adrenaline and chlorpromazine through the activation of the β-adrenergic receptor and showed a dose-dependent effect. Low-dose adrenaline similar to what might be used in human dental treatment did not result in a significant homodynamic change.Abstract

The time course of percentage change of mean blood pressure (MBP) (a) and pulse rate (PR) (b) after the injection of saline or 100 μg/kg adrenaline (AD) in chlorpromazine (Ch)-pretreated rats and saline-pretreated rats (Ch + saline: n = 4; Ch + AD: n = 6; saline + AD: n = 4). P values are for between-agent comparisons (vs the value for Ch + saline) at specified time intervals by using 2-way analysis of variance with Bonferroni's post hoc test. Data represent mean ± SD.

The blockade effect of propranolol (Pro) on hemodynamic changes by drug interaction between adrenaline (AD) and chlorpromazine (Ch) on mean blood pressure (MBP) (a) and pulse rate (PR) (b) (Ch + saline: n = 4; Ch + Pro + AD: n = 3). AD induced modest hypertension, but did not significantly influence pulse rate change in Pro + Ch–pretreated rats. P values are for between-agent comparisons (vs the value for Ch + saline) at specified time intervals by using 2-way analysis of variance with Bonferroni's post hoc test. Data represent means ± SD.

The effect of adrenaline at each concentration on mean blood pressure (MBP) (a) and pulse rate (PR) (b) in chlorpromazine-pretreated rats (saline: n = 4; 1 μg/kg: n = 6; 10 μg/kg: n = 4; 100 μg/kg: n = 6). Adrenaline at each concentration induced hypotension and tachycardia, and 100 μg/kg adrenaline induced significant hemodynamic changes. P values are for the comparisons at each concentration of adrenaline by using 1-way analysis of variance with Dunnett's post hoc test (vs saline). Data represent means ± SD.
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