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PERINATAL POLYDRUG ABUSE--COCAINE AND DRUG INTERACTIONS

围产期多种药物滥用——可卡因和药物相互作用

基本信息

批准号：
2897821
负责人：
HISAYO O MORISHIMA
金额：
$ 34.84万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
1990
资助国家：
美国
起止时间：
1990-07-01 至 2000-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2897821
关键词：
anesthetics cocaine drug abuse drug administration rate /duration drug interactions embryo /fetus toxicology intravenous administration intravenous drug abuse isoflurane laboratory rat perinatal pharmacokinetics placenta pregnancy pulmonary circulation reproductive system pharmacology tocolytic agents uterus

项目摘要

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.

我们项目的长期主要目标是研究种属、性别、年龄和妊娠相关的差异存在于可卡因和酒精及其代谢物的处置和毒性。特别强调了滥用多种药物的孕妇如何应对对这些物质，信息，这将提供一个更好的了解他们的医疗管理以及他们的护理发育中的胎儿在下一个资助期，我们建议研究药理学急性、危及生命的情况的管理对可卡因滥用孕妇及其未出生的孩子，麻醉和可卡因成瘾者的分娩经常复杂化产妇和胎儿在很大程度上被忽视了。自然流产、胎盘早剥、早产或破裂与可卡因滥用有关的膜不再罕见，美国的大城市。麻醉师经常紧急给可卡因注射麻醉剂中毒的产妇从临床角度来看，药物相互作用这些患者的药效学反应非常重要但麻醉对这些患者的潜在风险贝弗被充分处理。长期准备，不受干扰，清醒的大鼠是我们的研究模型。在可卡因诱导的亚惊厥状态下，吸入或局部给药的麻醉浓度麻醉剂该给药方案模型用于：1）测试可卡因的处置和血流动力学反应被改变，麻醉; 2）检查胎盘在可卡因代谢中的作用及其代谢物，以阐明胎盘如何防止这些物质转移到胎儿;和3）评价疗效宫缩抑制剂对可卡因刺激的子宫活动的影响。这将是第一次系统地评估怀孕期间滥用可卡因者和常用麻醉剂，宫缩抑制剂了解这些反应将使我们能够预测在哪些临床情况下选择麻醉剂或保胎剂药物滥用的孕妇可能是有益的，其中，情况下，它们可能是有害的。