Pharmacokinetics And Pharmacodynamics Of Drugs Of Abuse

影响药物成瘾性的因素有很多。给药途径是药物进入体内和中枢神经系统受体的速度的主要决定因素。临床研究正在进行中，这些研究确定了不同给药途径的重要性，以及药物和活性代谢物的血液浓度与伴随的药物效果的关系。对海洛因、可卡因、甲基苯丙胺、可待因和大麻通过静脉、吸烟、鼻腔和口服途径给药的研究正在进行中或处于数据分析阶段。药效学效应包括主观、认知和精神运动表现，生理指标和特定的脑活动，如功能磁共振成像评估。血浆、尿液、口腔液、汗液、头发和皮肤采用固相萃取-气相色谱-质谱法和液质联用法分析药物和代谢物。静脉和烟熏途径会产生快速的药理作用，同时血液中的药物和代谢物也会较早出现。在吸食大麻后观察到延迟分布到效应部位的证据，但吸食海洛因和可卡因后的药物效应与同时的血液浓度更接近。鼻腔给药后，尤其是口服给药后，起效时间会推迟。

There are many factors that influence the addictiveness of a drug. The route of administration is a major determinant of the speed of drug entry into the body and to receptors in the central nervous system. Clinical studies are in progress which determine the importance of different routes of administration and the relationship of blood concentrations of drug and active metabolites to concomitant drug effects. Studies of heroin, cocaine, methamphetamine, codeine and cannabis administration by the intravenous, smoked, intranasal and oral routes are underway or in the data analysis stage. Pharmacodynamic effects include subjective, cognitive and psychomotor performance, physiological measures and specific brain activity as assessed by fMRI. Plasma, urine, oral fluid, sweat, hair and skin are analyzed for drug and metabolites by solid phase extraction-gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry. The intravenous and smoked routes produce a rapid onset of pharmacological effects together with an early appearance of drug and metabolites in blood. Evidence of delays in distribution to effector sites are observed following cannabis smoking, but drug effects following heroin and cocaine administration coincided more closely with concurrent blood concentrations. Onset of effects is delayed following intranasal and especially after oral administration.