Pharmacokinetics And Pharmacodynamics Of Smoked Drugs Of Abuse

过去十年来，美国某些滥用药物的给药途径发生了巨大变化。例如，海洛因的静脉注射途径历来是最受欢迎的给药方法。随着鼻内和吸食海洛因的报告增加，这种情况正在发生变化。这些变化的原因可能包括社会和环境因素，如吸烟的方便性和便利性，避免针传播疾病，以及不同给药途径可能产生的药理学差异。与可卡因相反，在美国，烟草（尼古丁）和大麻（四氢大麻酚）几乎总是通过吸烟给药。药物给药途径是给定药物的毒性和成瘾性的决定因素。吸烟途径导致显著的发病率和死亡率。研究检查了给药途径（鼻内、静脉内和吸烟）对可卡因、甲基苯丙胺、大麻、海洛因和尼古丁的药代动力学参数和药物诱导的行为和生理效应的影响。在给药前和给药后定期收集生理和行为指标。同时采集血液样本，并通过气相色谱/质谱法和液相色谱/质谱法分析药物和代谢物。通过不同的途径评估主观效果的行为测量以及认知和心理表现，以比较反应的大小，包括滥用倾向的测量。通过替代途径给药后的血药浓度研究可确定药物生物利用度，这是给药途径选择中的一个重要因素。生理反应根据作用部位药物浓度的速度、幅度和持续时间而变化。鼻内给药的特点是血浆浓度较低，药理学作用起效较慢，其幅度通常低于其他给药途径。这些研究结果表明，吸食可卡因（“快克”）具有更高的滥用倾向和更大的依赖性比同等剂量的可卡因通过静脉或鼻内途径管理的属性。其他研究发现，吸食海洛因、可卡因和尼古丁的人的喜好得分相似。总之，这些研究表明，吸烟给药途径与高水平的滥用倾向有关，药物滥用的可能性不是药物的固有属性，而是取决于药物的输送方式。

A dramatic shift has occurred over the last decade in the route of administration of certain drugs of abuse in the United States. For example, the intravenous route for heroin has historically been the favored method of drug administration. This is changing with increased reports of intranasal and smoked administration of heroin. The reasons for these changes may include social and environmental factors such as the ease and convenience of smoking, avoidance of needle-transmitted diseases, and possible pharmacologic differences produced by the different routes of administration. In contrast to cocaine, tobacco (nicotine) and cannabis (tetrahydrocannabinol) have almost always been administered via smoking in the United States. The route of drug administration is a determinant of the toxicity and addictiveness of a given drug. The smoked route results in significant morbidity and mortality. Studies examine the influences exerted by routes of administration (intranasal, intravenous, and smoked) on pharmacokinetic parameters and drug-induced behavioral and physiologic effects of cocaine, methamphetamine, cannabis, heroin and nicotine. Physiological and behavioral measures are collected before and periodically after drug administration. Concurrent blood specimens are collected and analyzed by gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry for drugs and metabolites. Behavioral measures of subjective effects and cognitive and psychomotor performance are evaluated by the different routes to compare magnitude of responses including measures of abuse liability. Investigation of plasma concentrations following administration of drugs by alternative routes permits determination of drug bioavailability, an important factor in route selection. Physiologic responses vary according to the speed, magnitude and duration of drug concentrations at the site of action. Intranasal administration was characterized by lower plasma concentrations and a slower onset of pharmacologic effects that were generally of lower magnitude than those observed by other routes of administration. These findings suggest that smoked cocaine ("crack") has a higher abuse liability and greater dependence-producing properties than equivalent doses of cocaine administered by the intravenous or intranasal route. Other studies found that liking scores were similar for smoked doses of heroin, cocaine, and nicotine. Together, these studies indicate that the smoked route of drug administration is associated with high levels of abuse liability and that a drug's abuse potential is not an inherent property of the drug, but can vary depending on how the drug is delivered.