PERINATAL POLYDRUG ABUSE--COCAINE AND DRUG INTERACTIONS

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Long-term principal goal of our project have been to examine whether species-, gender-, age-, and pregnancy-related differences exist in the disposition and toxicity of cocaine and alcohol adn their metabolites. Special emphasis has been paid to how pregnant polydrug abusers respond to these substances, information which will provide a better understanding of their medical management as well as the care of their developing fetuses. In the next grant period we propose to investigate the pharmacological implication of the managemtn of acute, life-threatening situations in cocaine abusing pregnant women and their unborn children who are about with anesthesia and frequently complicate labor on the cocain-addicted parturients and their fetuses has been largely ignored. Spontaneous abortion, abruptio placentae, premature labor, or a ruptured membrane related to cocaine abuse are no longer uncommon occurrence in large cities in the United States. Anesthesiologists are frequently called upon to emergently administer anesthesia to acutely cocaine- intoxicated parturients. From a clinical standpoint, drug interaction and pharmacodynamic responses in these patients are extremely important but the potential risk of anesthesia to these patients has bever been adequately addressed. The chronically prepared, undisturbed, awake rat is our research model. Under a cocaine-induced subconvulsive state, pregnant or nonpregnant rats are administered and anesthetic concentration of inhalational or local anesthetic agent. This dose regimen model is ude to 1) test whether the disposition of cocaine and the hemodynamic responses are altered by anesthesia; 2) examine the role of placenta in the metabolism of cocaine and its metabolites, in order to elucidate how the placental prevents transfer of these substances to the fetus; and 3) evaluatej the efficacy of tocolytic agents on cocaine-stimulated uterine activity. This will be the first systematic evaluation of the interactions between cocaine abusers during pregnancy and commonly used anesthetic and tocolytic agents. The understanding of these responses will allow us to predict in which clinical situations selected anesthetic or tocolytic agents for drug abusing pregnant women may be beneficial, and in which situation they could be deleterious.