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The principal components are tar and nicotine, the amounts of which can vary greatly depending on the country in which cigarettes are sold. Regulation and voluntary agreement by manufacturers aspires to achieve a 'global cigarette' containing at most 12 mg of tar and 1 mg of nicotine.

The composition of tobacco smoke is complex (about 500 compounds have been identified) and varies with the type of tobacco and the way it is smoked. The chief pharmacologically active ingredients are nicotine (acute effects) and tars (chronic effects).

Smoke of cigars and pipes is alkaline (pH 8.5) and nicotine is relatively un-ionised and lipid-soluble so that it is readily absorbed in the mouth. Cigar and pipe smokers thus obtain nicotine without inhaling (they also have a lower death rate from lung cancer; which is caused by non-nicotine constituents).

Smoke of cigarettes is acidic (pH 5.3) and nicotine is relatively ionised and insoluble in lipids. Desired amounts are absorbed only if nicotine is taken into the lungs, where the enormous surface area for absorption compensates for the lower lipid solubility. Cigarette smokers therefore inhale (and have a high rate of death from tar-induced lung cancer). The amount of nicotine absorbed from tobacco smoke varies from 90% in those who inhale to 10% in those who do not.

Tobacco smoke contains 1-5% carbon monoxide and habitual smokers have 3-7% (heavy smokers as much as 15%) of their haemoglobin as carboxy-

11 UK prescribers can find general advice in the British National Formulary.

12 Editorial 1999 Tobacco money and medical research. Nature Medicine 5:125

haemoglobin, which cannot carry oxygen. This is sufficient to reduce exercise capacity in patients with angina pectoris. Chronic carboxyhaemoglobinaemia causes polycythaemia (which increases the viscosity of the blood).

Substances carcinogenic to animals (polycyclic hydrocarbons and nicotine-derived N-nitrosamines) have been identified in tobacco smoke condensates from cigarettes, cigars and pipes. Polycyclic hydrocarbons are responsible for the hepatic enzyme induction that occurs in smokers.

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