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Maximum blood concentrations after oral alcohol therefore depend on numerous factors including the total dose, sex, the strength of the solution, the time over which it is taken, the presence or absence of food, the time relations of taking food and alcohol and the kind of food eaten, as well as on the speed of metabolism and excretion. A single dose of alcohol, say 60 ml (48 g) (equivalent to 145 ml of whisky, 5-6 measures, or units; see Fig. 10.1), taken over a few minutes on an empty stomach will probably produce maximal blood concentration at 30-90 min and will not all be disposed of for 6-8 h or even more. There are very great individual variations.
Metabolism. About 95% of absorbed alcohol is metabolised, the remainder being excreted in the breath, urine and sweat; convenient methods of estimation of alcohol in all these are available.
Alcohol in the systemic circulation is oxidised in the liver; principally (90%) by alcohol dehydrogenase to acetaldehyde and then by aldehyde dehydrogenase to products that enter the citric acid cycle or are utilised in various anabolic reactions. Other alcohol-metabolising enzymes are microsomal cytochrome P450 2E1 (which is also induced by alcohol) and catalase.
Alcohol metabolism by alcohol dehydrogenase follows first-order kinetics after the smallest doses. Once the blood concentration exceeds about 10 mg/100 ml the enzymatic processes are saturated and elimination rate no longer increases with increasing concentration but becomes steady at 10-15 ml per hour in occasional drinkers. Thus alcohol is subject to dose-dependent kinetics, i.e. saturation or zero-order kinetics, with potentially major consequences for the individual.
Induction of hepatic drug metabolising enzymes occurs with repeated exposure to alcohol and this contributes to tolerance in habitual users, and to toxicity. Increased formation of metabolites causes organ damage in chronic over-consumption (acetaldehyde in the liver and probably fatty ethyl esters in other organs) and increases susceptibility to liver injury when heavy drinkers are exposed to anaesthetics, industrial solvents and to drugs. But chronic use of large amounts reduces hepatic metabolic capacity by causing cellular damage. An acute substantial dose of alcohol (binge drinking) inhibits hepatic drug metabolism.
Inter-ethnic variation is recognised in the ability to metabolise alcohol (see p. 184).
Blood concentration of alcohol (Fig. 10.1) has great medicolegal importance. Alcohol in alveolar air is in equilibrium with that in pulmonary capillary blood and reliable, easily handled measurement devices (breathalyser) are used by police at the roadside on both drivers and pedestrians.24
Alcohol acts on the central nervous system in a manner broadly similar to volatile anaesthetics, exerting on cells a generally depressant effect that is probably mediated through particular membrane ion channels and receptors. Alcohol enhances (inhibitory) GABA-stimulated flux of chloride through receptor-gated membrane ion channels, a receptor subtype
24 An arrested man was told, in a police station, by a doctor, that he was drunk. The man asked, 'Doctor, could a drunk man stand up in the middle of this room, jump into the air, turn a complete somersault, and land down on his feet?' The doctor was injudicious enough to say, "Certainly not"—and was then and there proved wrong. (Worthing C L 1957 British Medical Journal 1: 643.) The introduction of the breathalyser, which has a statutory role only in road traffic situations, has largely eliminated such professional humiliations.
effect that may be involved in the motor impairment caused by alcohol. Other possible modes of action include inhibition of calcium entry via voltage-gated (L type) calcium channels, and inhibition of the (excitatory) NMDA (N-methyl-D-aspartate) receptor. (See page 184 for chronic effects of alcohol on the brain.)
It is not a stimulant; hyperactivity, when it occurs, is due to removal of inhibitory effects. Alcohol in ordinary doses may act chiefly on the arousal mechanisms of the brainstem reticular formation, inhibiting polysynaptic function and enhancing presynaptic inhibition. Direct cortical depression probably only occurs with high doses. With increasing doses the subject passes through all the stages of general anaesthesia and may die of respiratory depression.25
Psychic effects are the most important socially (Fig. 10.2), and it is to obtain these that the drug is habitually used in so many societies, to make social intercourse not merely easy but even pleasant. They have been admirably described by Sollmann:
The first functions to be lost are the finer grades of judgement, reflection, observation and attention— the faculties largely acquired through education, which constitute the elements of the restraint and prudence that man usually imposes on his actions. The orator allows himself to be carried by the impulse of the moment, without reflecting on ultimate consequences, and as his expressions become freer, they acquire an appearance of warmth, of feeling, of inspiration. Not a little of this inspiration is contributed by the audience if they are in a similar condition of increased appreciation ... Another characteristic feature, evidently resulting from paralysis of the higher functions, is the loss of power to control moods.26
Environment, personality, mood and dose of alcohol are all relevant to the final effect on the individual. These and other effects that are characteristic of alcohol, have been celebrated in the following couplets:27
25 Loss of consciousness occurs at blood concentrations around 300 mg/100 ml; death at about 400 mg/100 ml. But the usual cause of death in acute alcohol poisoning is inhalation of vomit.
26 Sollmann T 1957 Manual of pharmacology, 8th edn.
You may drunk I am think, but I tell you I'm not,
I'm as sound as a fiddle and fit as a bell,
And stable quite ill to see what's what...
I shall stralk quite weight and not yutter an ell.
My feech will not spalter the least little jot:
And I said to him,'Sergeant, I'll come like a lamb
The floor it seems like a storm In a yacht,
But I'm not so think as you drunk I am.
I'm sorry. I just chair over a fell
If I hadn't consumed that last whisky of tot!
As I said now, this fellow, called Abraham
Ah? One more? Since It's you! just a do me will spot
But I'm not so think as you drunk I am.
Innumerable tests of physical and mental performance have been used to demonstrate the effects of alcohol. Results show that alcohol reduces visual acuity and delays recovery from visual dazzle; it impairs taste, smell and hearing, muscular coordination and steadiness and prolongs reaction time. It also causes nystagmus and vertigo. At the same time the subjects commonly have an increased confidence in their ability to perform well when tested and underestimate their errors, even after quite low doses. Attentiveness and ability to assimilate, sort and quickly take decisions on con-
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