The project is a series of clinical trials which are evaluating the efficacy and safety of experimental therapeutic agents used for the control of pain and perioperative apprehension in ambulatory patients undergoing minor surgical procedures. Current studies are evaluating the interaction of proglumide and morphine for postoperative pain, the analgesic efficacy of spiradoline in comparison to morphine, the clinical efficacy of flumazenil for reversing the central effects of intravenous diazepam and the physiological effects of high doses of epinephrine-containing local anesthetics. The surgical removal of impacted third molars serves as a model for minor surgical procedures with associated intraoperative and postoperative pain and perioperative apprehension. All studies are double-blind with randomly allocated, parallel treatment groups and multiple dependent measures of therapeutic efficacy and clinical safety. Administration of 0.05 mg of proglumide was demonstrated to significantly potentiate and prolong the analgesic efficacy of 4 mg of morphine for postoperative pain. Higher doses of proglumide (0.5 mg and 5.0 mg) were without effect. These data thus provide indirect evidence for the hypothesis that cholecystokinin participates in the modulation of pain. Administration of relatively high doses of epinephrine in local anesthesia resulted in a greater than 25-fold increase in plasma epinephrine levels with elevated levels persisting throughout the 20 minute observation period. Results of this study confirm our previous observations and refute the traditional viewpoint that the concentrations of epinephrine in local anesthetics administered for dental procedures does not result in changes in blood levels or physiologic effects. Taken together, the results of these studies are providing data to establish a rational basis for the pharmacologic management of acute pain and perioperative apprehension associated with minor surgical procedures in ambulatory patients.
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