Smoking in patients receiving psychotropic medications - A pharmacokinetic perspective
Smoking in patients receiving psychotropic medications - A pharmacokinetic perspective
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DOI：
10.2165/00023210-200115060-00005
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发表时间：
2001-01-01
期刊：
影响因子：
6
通讯作者：
Jann, MW
中科院分区：
文献类型：
--
作者：
Desai, HD;Seabolt, J;Jann, MW
许多精神病患者吸烟，并且被认为比那些没有精神疾病的人吸烟更严重。吸烟是导致个体间对药物反应差异的环境因素之一。香烟烟雾中存在的多环芳烃（PAH）可诱导肝脏芳烃羟化酶，从而增加作为这些酶底物的药物的代谢清除率。多环芳烃可诱导3种肝细胞色素P450（CYP）同工酶，主要是CYP 1A1、1A2和2E1。药物治疗也会受到尼古丁的药效学影响。吸烟对人体药物处置的最常见影响是生物转化率增加，与药物代谢酶的诱导一致。肝酶的诱导已被证明可增加丙咪嗪、氯丙咪嗪、氟伏沙明和曲唑酮的代谢并降低其血浆浓度。吸烟对阿米替林和去甲替林血浆浓度的影响是可变的。安非他酮（安非他酮）似乎不受吸烟的影响。吸烟与噻替吨、氟奋乃静、氟哌啶醇和奥氮平的清除率增加相关。吸烟可降低氯丙嗪和氯氮平的血浆浓度。临床上，与非吸烟者相比，接受氯丙嗪和苯二氮卓类药物的吸烟者的嗜睡减少。在吸烟者中发现苯二氮卓类药物阿普唑仑、劳拉西泮、奥沙西泮、地西泮和去甲基地西泮的清除率增加，而利血平似乎不受吸烟的影响。卡马西平似乎受香烟烟雾的影响最小，可能是因为肝酶已经被其自身的自诱导特性所刺激。吸烟可影响许多精神药物的药代动力学和药效学特性。临床医生应将吸烟视为这些药物处置的一个重要因素。
Many psychiatric patients smoke, and are believed to be heavier smokers than those without psychiatric disorders. Cigarette smoking is one of the environmental factors that contributes to interindividual variations in response to an administered drug. Polycyclic aromatic hydrocarbons (PAHs) present in cigarette smoke induce hepatic aryl hydrocarbon hydroxylases, thereby increasing metabolic clearance of drugs that are substrates for these enzymes. PAHs have been shown to induce 3 hepatic cytochrome P450 (CYP) isozymes, primarily CYP1A1, 1A2 and 2E1. Drug therapy can also be affected pharmacodynamically by nicotine. The most common effect of smoking on drug disposition in humans is an increase in biotransformation rate, consistent with induction of drug-metabolising enzymes. Induction of hepatic enzymes has been shown to increase the metabolism and to decrease the plasma concentrations of imipramine, clomipramine, fluvoxamine and trazodone. The effect of smoking on the plasma concentrations of amitriptyline and nortriptyline is variable. Amfebutamone (bupropion) does not appear to be affected by cigarette smoking. Smoking is associated with increased clearance of tiotixene, fluphenazine, haloperidol and olanzapine. Plasma concentrations of chlorpromazine and clozapine are reduced by cigarette smoking. Clinically, reduced drowsiness in smokers receiving chlorpromazine, and benzodiazepines, compared with nonsmokers has been reported. Increased clearance of the benzodiazepines alprazolam, lorazepam, oxazepam, diazepam and demethyl-diazepam is found in cigarette smokers, whereas chlordiazepoxide does not appear to be affected by smoking. Carbamazepine appears to be minimally affected by cigarette smoke, perhaps because hepatic enzymes are already stimulated by its own autoinductive properties. Cigarette smoking can affect the pharmacokinetic and pharmacodynamic properties of many psychotropic drugs. Clinicians should consider smoking as an important factor in the disposition of these drugs.