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.Key Words: Local anesthesia, Drug interaction, Adrenaline, Epinephrine, AntipsychoticsVasoconstrictors are included in local anesthetics to increase the duration of anesthesia, to prevent local anesthesia systemic toxicity, and to promote hemostasis in the local operative field.¹ Adrenaline (epinephrine) is the most common vasoconstrictor that is added to local anesthetics, and lidocaine and articaine with adrenaline are the most widely used local anesthetics for dental treatment. However, adrenaline has drug interactions with some medicines. It is widely believed that the combination of adrenaline with an antipsychotic can cause hypotension because antipsychotics have α-adrenergic blocker effects that can result in decreased peripheral resistance, and adrenaline has been shown to have significant β2-adrenergic mediated vasodilatory effects that also can cause hypotension. Therefore, the combination of adrenaline and an antipsychotic is contraindicated in Japan for fear of causing significant hypotension. However, there is insufficient evidence supporting this claim, and, in clinical settings, there are many situations in which the use of local anesthetics with adrenaline is appropriate for dental treatment of patients receiving antipsychotic therapy. Thus, the purpose of the present study was to clarify the changes in hemodynamics caused by a drug interaction between adrenaline and an antipsychotic and to evaluate the safety of the combined use of adrenaline with an antipsychotic in an animal study.