Drug Interaction between Adrenaline and Chlorpromazine

 Adrenaline is included in local anesthesia for the purpose of vasoconstriction, contributing to increasing effects of anesthesia, preventing local anesthesia intoxication and promoting hemostasis in the local operative field. However, adrenaline has drug interactions with some medicines. It is widely regarded that combination of adrenaline with antipsychotics causes hypotension, because antipsychotics have effects of α blocker, and β2 effects of adrenaline are shown. Therefore, combinations of adrenaline and antipsychotics are contraindicated in Japan. However there has been no clear evidence to date supporting this drug interaction. The purpose of this study was thus to clarify the changes in hemodynamics caused by drug interaction between adrenaline and an antipsychotic.

Methods:

 Male Sprague-Dawley Rats were anesthetized with intraperitoneal injection of sodium pentobarbital. A catheter was inserted into the femoral artery for measurement of blood pressure and pulse rate. Chlorpromazine (5mg/kg) was administered by intraperitoneal injection, and after 20 minutes, Adrenaline (1ug/kg, 10ug/kg and 100ug/kg) was administered by intraperitoneal injection. We measured changes in the ratio of mean arterial blood pressure and pulse rate after the injection of adrenaline. 

Results:

 The injection of adrenalin caused hypotension (saline: 101.3 ± 3.9%, 1ug/kg: 99.0 ± 7.6%, 10ug/kg: 84.7 ± 3.1%, 100ug/kg: 71.5 ± 3.7% (Mean ± S.E.M)) and tachycardia (saline: 97.2 ± 2.9% 1ug/kg: 99.6 ± 2.6 %, 10ug/kg: 106.8 ± 4.7%, 100ug/kg: 123.2 ± 4.1 % (Mean ± S.E.M)) in a dose-dependent manner. The injection of 100ug/kg adrenaline caused marked hypotension and tachycardia.

Conclusions:

 The hypotension was caused by drug interaction between adrenaline and chlorpromazine, and showed a dose-dependent effect. Low-dose adrenaline did not result in a significant homodynamic change, however. Our results suggest that local dental anesthesia with adrenaline is safe to use to in patients undergoing treatment with antipsychotics.