The narcotic analgesics have an important role in the perioperative management of surgical patients - preoperatively as hypnotics, intraoperatively as sole or adjuvant anesthetics and postoperatively for pain relief. With increasing age, there is a well demonstrated decrease of the narcotic dose requirement. Because narcotics have a narrow therapeutic index and an age-related change of dose requirement, the safe use of narcotics in the aged can become clinically difficult. This research will develop a pharmacodynamic model that relates the morphine or fentanyl plasma concentration to the degree of narcotic effect on the brain. The narcotic-induced slowing of the electroencephalogram (EEG) will be used as a noninvasive, continuous measure of the drug effect ot estimate an individual patient's brain sensitivity. The pharmacokinetics of morphine and fentanyl will be determined in surgical patients aged 20-90 years old to see if increasing age and its physiological alterations effect pharmacokinetic variables, such as the degree of protein binding, the rate or extent of narcotic distribution or the rate of elimination from the body. The pharmacodynamics of morphine and fentanyl will be determined in surgical patients, aged 20-90 years using the above indicated EEG measures of narcotic brain effect. Pharmacodynamic modelling will be used to relate the narcotic plasma concentrations to the drug induced EEG changed and to determine if aging alters the onset, degree of (brain sensitivity) and duration of morphine/fentanyl CNS effect. The above research will be used to provide better scientific guidelines for the clinical use of morphine and fentanyl in the aged surgical patient. By determining the mechanism of the altered narcotic dose requirement with increasing age in man, subsequent animal and in vivo pharmacology can more specifically be directed to obtain biochemical and molecular explanations of the effects of aging on narcotic response.
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