CIGARETTE SMOKING AND PHARMACOKINETICS

Smoking stimulates hepatic metabolism of many drugs Cigarette smoking alters the pharmacokinetics of many drugs. An increase in hepatic metabolism is probably caused by the

polycyclic hydrocarbons, while serum nicotine levels may interact directly with some drugs. The effects on liver function are not

the same as those produced by phenobarbitone since they persist far longer on withdrawal from smoking than on withdrawal

from phenobarbitone. The interaction with drug metabolism is directly related to the number of cigarettes smoked but older

patients seem more resistant. Although there are some conflicting studies, there are certain drugs where it is clear that cigarette smoking decreases serum levels

and drug half-life as well as increasing drug clearance. Such effects have been most clearly shown with theophylline, pentazocine,

propranolol, propoxyphene (dextropropoxyphene), and heparin, and less clearly so with tricyclic antidepressants, phenothiazines,

caffeine and benzodiazepines. Patients who smoke a lot tend to suffer fewer side effects from a drug because of the lowered serurri

levels, and to achieve therapeutic drug levels, doses may have to be adjusted. Diabetic smokers generally require more insulin.

Patients who use oral contraceptives and smoke increase the possibility of cardiovascular adverse effects (particularly with age)

and should stop smoking or use alternative methods of contraception. Smoking decreases serum levels of ascorbic acid (vitamin C)

and cyanocobalamin (vitamin 8 12) although the clinical importance of this is unknown. Smoking may increase the risk of

tolbutamide-induced cardiac arrhythmias. Bioavailability of oral lignocaine (lidocaine) is reduced, but the pharmacokinetics of IV

lignocaine are relatively unaffected. The therapeutic response to phenacetin is not significantly affected since plasma levels are

reduced but the plasma level of the active metabolite, paracetamol (acetaminophen) is increased. Smoking may antagonise

dexamethasone-induced suppression of plasma corticosteroid concentrations. There is some evidence that smoking may increase

the absorption (and therefore serum levels) of glutethimide. Smoking does not affect the pharmacokinetics of codeine, pethidine,

phenytoin or the hypoprothrombinaemic response to warfarin. Drug Interactions Newsletter 2: 13 (Apr 1982)

4 INPHARMA 22 May 1982 0156-2703/82/0522-0004/0$01.00/0 © ADIS Press