Clinical Pharmacology and Therapeutics

CENTRAL DEPRESSANTS 441
Key points
Acute effects of alcohol
• Central effects include disinhibition, impaired
judgement, inco-ordination, trauma (falls, road traffic
accidents), violence and crime.
• Coma and impaired gag reflex; asphyxiation on vomit.
• Convulsions, enhancement of sedative drugs.
• Atrial fibrillation, vasodilation.
• Gastritis, nausea, vomiting, Mallory – Weiss syndrome.
• Hepatitis.
• Hypoglcycaemia, metabolic acidosis, etc.
Key points
Chronic effects of alcohol
• Dependence
• Behavioural changes
• Encephalopathy (sometimes thiamine deficient),
dementia, convulsions
• Cardiomyopathy
• Gastritis, nausea and vomiting; peptic ulceration
• Pancreatitis
• Cirrhosis
• Myopathy
• Bone marrow suppression
• Gout
• Hypertension
• Fetal alcohol syndrome.
Medical uses of alcohol
Alcohol is used topically as an antiseptic. Systemic alcohol is
used in poisoning by methanol or ethylene glycol, since it
competes with these for oxidation by alcohol dehydrogenase,
slowing the production of toxic metabolites (e.g. formaldehyde,
oxalic acid).
Management of alcohol withdrawal
A withdrawal syndrome develops when alcohol consumption
is stopped or severely reduced after prolonged heavy alcohol
intake. Several features of acute withdrawal are due to autonomic
overactivity, including hypertension, sweating, tachycardia,
tremor, anxiety, agitation, mydriasis, anorexia and
insomnia. These are most severe 12–48 hours after stopping
drinking, and they then subside over one to two weeks. Some
patients have seizures (‘rum fits’ generally 12–48 hours post
abstinence). A third set of symptoms consists of alcohol withdrawal
delirium or ‘delirium tremens’ (acute disorientation,
severe autonomic hyperactivity, and hallucinations – which
are usually visual). Delirium tremens often follows after withdrawal
seizures and is a medical emergency. If untreated,
death may occur as a result of respiratory or cardiovascular
collapse. Management includes thiamine and other vitamin
replacement, and a long-acting oral benzodiazepines (e.g.
chlordiazepoxide or diazepam), given by mouth if possible.
The initial dose requirement is determined empirically and is
followed by a regimen of step-wise dose reduction over the
next two to three days. The patient should be nursed in a quiet
environment with careful attention to fluid and electrolyte
balance. Benzodiazepines (intravenous if necessary, Chapters
18 and 22) are usually effective in terminating prolonged withdrawal
seizures – if they are ineffective the diagnosis should
be reconsidered (e.g. is there evidence of intracranial haemorrhage
or infection). Psychiatric assessment and social support
are indicated once the withdrawal syndrome has receded.
Key points
Delirium tremens
• Mortality is 5–10%.
• There is a state of acute confusion and disorientation
associated with frightening hallucinations and
sympathetic overactivity. Delirium tremens occurs in less
than 10% of alcoholic patients withdrawing from
alcohol.
• Management includes:
– nursing in a quiet, evenly illuminated room;
– sedation (either clomethiazole or diazepam);
– vitamin replacement with adequate thiamine;
– correction of fluid and electrolyte balance;
– psychiatric referral.
Long-term management of the alcoholic
Psychological and social management: Some form of
psychological and social management is important to help
the patient to remain abstinent. Whatever approach is used,
the focus has to be on abstinence from alcohol. A very small
minority of patients may be able to take up controlled
drinking subsequently, but it is impossible to identify this
group prospectively, and this should not be a goal of
treatment. Voluntary agencies such as Alcoholics
Anonymous are useful resources and patients should be
encouraged to attend them.
Alcohol-sensitizing drugs: These produce an unpleasant
reaction when taken with alcohol. The only drug of this type
used to treat alcoholics is disulfiram, which inhibits aldehyde
dehydrogenase, leading to acetaldehyde accumulation if
alcohol is taken, causing flushing, sweating, nausea,
headache, tachycardia and hypotension. Cardiac dysrhythmias
may occur if large amounts of alcohol are consumed. The
small amounts of alcohol included in many medicines may be
sufficient to produce a reaction and it is advisable for the
patient to carry a card warning of the danger of alcohol
administration. Disulfiram also inhibits phenytoin
metabolism and can lead to phenytoin intoxication.
Unfortunately, there is only weak evidence that disulfiram
has any benefit in the treatment of alcoholism. Its use should
be limited to highly selected individuals in specialist clinics.
Acamprosate: The structure of acamprosate resembles that of
GABA and glutamate. It appears to reduce the effects of
excitatory amino acids and, combined with counselling, it
may help to maintain abstinence after alcohol withdrawal.