Pharmacokinetics And Pharmacodynamics Of Smoked Drugs Of Abuse

在过去十年中，美国某些滥用药物的管理路线发生了戏剧性的变化。例如，静脉注射海洛因历来是最受欢迎的给药方法。随着鼻内和烟熏给药报告的增加，这种情况正在改变。这些变化的原因可能包括社会和环境因素，如吸烟的容易和方便，避免针头传播疾病，以及不同给药途径可能产生的药理学差异。与可卡因相比，烟草（尼古丁）和大麻（四氢大麻酚）在美国几乎总是通过吸烟来施用。给药途径是决定药物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。研究考察了给药途径（鼻内、静脉注射和吸烟）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引起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。同时采集血液标本，用气相色谱/质谱法和液相色谱/质谱法分析药物和代谢物。主观影响和认知和精神运动表现的行为测量通过不同的途径进行评估，以比较反应的幅度，包括虐待责任的测量。通过其他途径给药后的血浆浓度调查可以确定药物的生物利用度，这是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、大小和持续时间而变化。鼻内给药的特点是血浆浓度较低，药理作用开始较慢，通常比其他给药途径所观察到的程度要低。这些发现表明，与静脉注射或鼻内注射等量的可卡因相比，吸食可卡因（“快克”）有更高的滥用风险和更大的依赖性。其他研究发现，吸食海洛因、可卡因和尼古丁的人的喜欢分数是相似的。总之，这些研究表明，药物的吸烟途径与高水平的滥用风险有关，药物的滥用潜力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.