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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
2R01DA006648-07A1
Application #
2013036
Study Section
Special Emphasis Panel (ZDA1-MXC-A (05))
Project Start
1990-07-01
Project End
2000-03-31
Budget Start
1997-05-10
Budget End
1998-03-31
Support Year
7
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Anesthesiology
Type
Schools of Medicine
DUNS #
167204994
City
New York
State
NY
Country
United States
Zip Code
10032
Morishima, H O; Okutomi, T; Ishizaki, A et al. (2001) The disposition of benzoylecgonine in maternal and fetal rats. Neurotoxicol Teratol 23:247-53
Iso, A; Nakahara, K; Barr, G A et al. (2000) Long-term intravenous perinatal cocaine exposure on the mortality of rat offspring. Neurotoxicol Teratol 22:165-73
Morishima, H O; Ishizaki, A; Zhang, Y et al. (2000) Disposition of bupivacaine and its metabolites in the maternal, placental, and fetal compartments in rats. Anesthesiology 93:1069-74
Morishima, H O; Whittington, R A; Zhang, Y et al. (1999) The disposition of cocaethylene in rat maternal, placental, and fetal compartments. Am J Obstet Gynecol 180:1289-96
Morishima, H O; Whittington, R A; Iso, A et al. (1999) The comparative toxicity of cocaine and its metabolites in conscious rats. Anesthesiology 90:1684-90
Whittington, R A; Iso, A; Khan, K et al. (1999) Role of gender in the toxicity of norcocaine. J Lab Clin Med 133:590-6
Nakahara, K; Iso, A; Chao, C R et al. (1996) Pregnancy enhances cocaine-induced stimulation of uterine contractions in the chronically instrumented rat. Am J Obstet Gynecol 175:188-93
Morishima, H O; Whittington, R A (1995) Species-, gender-, and pregnancy-related differences in the pharmacokinetics and pharmacodynamics of cocaine. NIDA Res Monogr 158:2-21
Virag, L; Jamdar, S; Chao, C R et al. (1994) Sensitive assay for cocaine and benzoylecgonine using solid-phase extraction and gas chromatography. J Chromatogr B Biomed Appl 658:135-41
Nakahara, K; Iso, A; Morishima, H O (1994) [The effect of cocaine on uterine contractions in the rat] Nippon Sanka Fujinka Gakkai Zasshi 46:435-41

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