Smoking and Serum Drug Concentrations

Approximately 4800 compounds are found in tobacco smoke including nicotine and carcinogenic compound, for example polycyclic aromatic hydrocarbons (PAHs) and N-nitroso amines. Compounds in tobacco smoke can induce certain cytochrome P450 enzymes responsible for metabolism of many drugs. PAHs induce CYP1A1, CYP1A2, and possibly CYP2E1. Smoking may also induce other drug metabolism pathways such as conjugation (65). Cigarette smoke is responsible for pharmacokinetic drug interactions, not nicotine. Therefore, nicotine replacement therapy does not cause hepatic enzyme induction (66).

Theophylline is metabolized by CYP1A2. In one study, the half-life of theophylline was reduced by almost twofolds in smokers compared with that in non-smokers (65). Lee et al. (67) reported that theophylline clearance was increased by 51.1% and that steady state serum concentrations were reduced by 24.5% in children who were exposed to passive smoking. Clinically significant drug interactions with smoking have also been reported for caffeine, chlorpromazine, clozapine, flecainide, fluvoxamine, haloperidol, mexiletine, olanzapine, proprandol, and tacrine. With all medications, serum concentrations of drugs are significantly reduced in smokers because of increased metabolism of drugs. Smokers may therefore require higher doses than non-smokers to achieve pharmacological responses (66). Warfarin disposition in smokers is also different compared with that in non-smokers. One case report described an increase in INR to 3.7 from a baseline of 2.7-2.8 in an 80-year-old man when he stopped smoking. Subsequently, his warfarin dose was reduced by 14% (68). Another report also demonstrated an increase in INR in a 58-year-old male after cessation of smoking. His warfarin dose was lowered by 23% (69).

Pharmacodynamic drug interactions in smokers may be due to nicotine, which may counteract the pharmacological effects of a drug. The half-life of nicotine is approximately 2 h, and the pharmacological effects of nicotine, such as heart rate increases, blood pressure, diminishes rapidly after cessation of smoking. On the contrary, if nicotine replacement therapy is initiated in a hospitalized patient, heart rate may increase by 10-15 beats/min and blood pressure may increase by 5-10 mmHg (70). The transdermal nicotine patch may have a lesser effect on blood pressure and heart rate (71). Smokers taking benzodiazepines, such as diazepam and chlordiazepoxide, experience less drowsiness than non-smokers, and this interaction appears to be pharma-codynamic in nature because several studies did not find any significant difference between metabolism of benzodiazepines between smokers and non-smokers. Therefore, larger doses may be needed to sedate a smoker (66). Smokers may also need higher doses of opioids (codeine, propoxyphene, and pentazocine) for pain relief (65). In one study, to determine whether smokers require more opioid analgesic, it was found that 20 smokers (10 cigarettes a day or more for at least 1 year) required 23% more (when adjusted for body weight) and 33% more (when adjusted for body mass index) opioid analgesics compared with 69 non-smoking patients (72).

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