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

• 批准号: 2683824
• 负责人: HISAYO O MORISHIMA
• 金额: $ 34.48万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 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/2683824
• 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

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一直是检查 与物种、性别、年龄和怀孕相关的差异存在于 可卡因和酒精及其代谢物的处置和毒性。 特别强调了怀孕的多药滥用者的反应 对于这些物质，信息将提供更好的 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 紧急、危及生命的情况管理的含义 滥用可卡因的孕妇及其未出生的孩子 麻醉并经常使古柯碱成瘾者的分娩复杂化 产妇及其胎儿在很大程度上被忽视了。 自然流产、胎盘早剥、早产或胎盘破裂 与可卡因滥用有关的膜在中国不再少见 美国的大城市。麻醉师经常 被要求紧急给可卡因注射麻醉- 喝醉了的产妇。从临床角度来看，药物相互作用 这些患者的药效学反应是极其重要的 但麻醉对这些患者的潜在风险一直是 得到了充分的解决。 长期准备的、不受干扰的清醒大鼠是我们的研究模型。 在可卡因诱导的亚惊厥状态下，怀孕或未怀孕的大鼠 是否吸入或局部注射麻醉剂浓度 麻醉剂。此剂量方案模型用于1)测试是否 可卡因的处置和血流动力学反应被改变 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 将这些物质转移到胎儿体内；以及3)评估疗效 解宫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两国之间的互动 孕期可卡因滥用者及常用麻醉剂和 酵母菌发酵剂。对这些反应的理解将使我们能够 预测在哪些临床情况下选择麻醉剂或宫缩 药物滥用孕妇可能是有益的，在其中 情况下，它们可能是有害的。