Alcohol
A mixture of ethyl alcohol and water. A clear, colourless, mo-
bile, volatile, hygroscopic liquid with a characteristic spiritu-
ous odour and burning taste; readily flammable, burning with
a smokeless blue flame.
Misdbic with water (with rise of temperature and contraction
of volume), with chloroform, with ether, with glycerol. and
with almost all other organic solvents. Store at 8Β° to 15Β° away
from fire in airtight containers. Protect from light.
Anhydrous Ethanol (Ph. Eur.) (Absolute Alcohol; Dehy-
drated Alcohol) contains not less than 99.5% v/v or
99.2% w/w of ,H,OH.
Dehydrated Alcohol (USP 23) contains not less than
99.5% v/v or 99.2% w/w of C-,H;OH (sp. gr. not more than
0.7964 at 15.56Β°).
Dilute Ethanols (BP 1998) includes several dilute alcohols
containing between 20 and 90% v/v of C?H,OH. and one of
these, ethanol (90%), is also known as rectified spirit.
DilutedAlcohoKUSNF 18)contains48.4to49.5% v/vor41
to 42% w/w of C;H;OH and is prepared by mixing equal vol-
umes ofAlcohoKUSP 23) and water.
Alcoholic strength is expressed as a percentage by volume of
alcohol. It was previously often expressed in terms of proof
spirit. Proof spirit contained about 57,1% v/v or 49.2% w/w
ofC;H;OH, and was defined as 'that which at the temperature
of51Β°F weighs exactly twelve-thirteenths of an equal meas-
ure of distilled water'. Spirit of such a strength that 100 vol-
umes contained as much ethyl alcohol as 160 volumes of
proof spirit was described as '60 OP' (over proof). Spirit of
which 100 volumes contained as much alcohol as 40 volumes
of proof spirit was described as '60 -UP' (under proof)- An
alternative method of indicating spirit strength was used on
the labels of alcoholic beverages in the UK when the strength
was given as a number of degrees, proof spirit being taken as
100Β°. In the USA alcoholic strength is expressed in degrees.
the value of which is equal to twice the percentage byvolume.
Thus 70Β° proof (old UK system) is equivalent to 40% v/v, and
therefore to 80Β° proof (USA system).
Adverse Effects
Adverse effects of alcohol arise chiefly from the in-
take of alcoholic beverages. The concentration of al-
cohol in the blood producing a state of intoxication
varies between individuals. At low to moderate con-
centrations alcohol acts as an apparent stimulant:
depression of cortical function causes loss of judge-
ment, emotional lability, muscle incoordination, vis-
ual impairment, slurred speech, and ataxia.
Hangover effects may include nausea, headache,
dizziness, and tremor. Alcohol depresses medullary
action: lethargy, amnesia, hypothermia, hypogly-*
caemia (especially in children), stupor, coma, respi-
ratory depression, cardiomyopathy, hypertension or
hypotension, and cardiovascular collapse may oc-
cur. The median lethal blood-alcohol concentration
is generally estimated to be approximately 400 to
500 mg per 100 mL. Death may occur at lower
blood-alcohol concentrations due to inhalation of
vomit during unconsciousness.
Chronic excessive consumption of alcohol may
cause damage to many organs, particularly the brain*
and the liver. Brain damage may lead'to Wemicke-*
Korsakoff syndrome. Fat deposits may occur in the
liver and there may be a reduction in various blood-
cell counts. Nutritional diseases may occur due to
inadequate diet. High alcohol consumption has been
associated with pancreatitis, and an increased risk of
cardiovascular disease, although moderate con-
sumption may have a protective effect against is-
chaemic heart disease.
Alcohol consumption has also been associated with
an increased risk of some types of cancer.
The term 'alcoholism' may be used to denote dependence
on alcohol which is of the barbiturate-
alcohol type and usually involves
tolerance to other sedatives and anaesthetics. Fol-
lowing prolonged periods of excessive alcohol con-
sumption, a drop in blood-alcohol concentration
may precipitate a withdrawal syndrome character-
ised by tremor, agitation, feelings of dread, nausea.
vomiting, and sweating; hallucinations, seizures,
and delirium tremens may also develop.
A fetal alcohol syndrome has been identified in
which infants born to some alcoholic mothers have
characteristic features and abnormalities. There
have been some reports of the syndrome and other
adverse effects on the fetus being associated with
moderate alcohol intake in pregnancy; it is generally
suggested that alcohol is best avoided during preg-
nancy.
Frequent application of alcohol to the skin produces
irritation and dry skin.
Reviews of the adverse effects of alcohol.
Effects on the skin. A 70% solution of alcohol, containing
povidone-iodine, caused partial thickness chemical bums
when held under pressure against the skin of 3 young chil-
dren.' Other adverse effects on the skin reported with the top-
ical application of alcohols have included necrosis occurring
following skin cleansing of preterm neonates with methylated
spirits' and haemon-hagic skin necrosis due to the alcbhol
content ofchlorhcxidine in spirit used as a disinfectant in um-
bilical artery catheterisation in preterm infants.
Treatment of Adverse Effects
In acute poisoning the patient should be kept warm
and given supportive and symptomatic care. The use
of intravenous infusions of fructose to treat severe
alcohol poisoning is not recommended as they may
produce metabolic disturbances. Haemodialysis is
of value in severe alcoholic poisoning.
The management of the alcohol withdrawal syn
drome and long-term abstinence following with-
drawal are discussed below.
Alcohol withdrawal and abstinence: The alcohol with-
drawal syndrome presents in the early stages as a classic;
hyperadrenergic state with tremor, tachycardia, sweating, and
hypertension. Sometimes this is accompanied by mild disori
entation, anxiety, impaired concentration, depression, agita
tion, and gastro-intestinal symptoms. Insomnia, nightmare'
and transient hallucinations can also be present. The condi
tion may be self-limiting without the need for therapeutic in-
tervention or it may progress to the severe and potentiall
fatal condition of delirium tremens (DTs), often characterised
by delirium, disorientation, and hallucinations. In some cases
generalised tonic-clonic seizures occur within 24 hours of al
cohol withdrawal and are followed by delirium tremens.
Withdrawal: The general management of the alcohol with-
drawal syndrome has been the subject of many reviews and
discussions.''* In most cases symptoms do not require treat
ment and disappear within a few days but more severe cases
may require managed withdrawal from alcohol to avoid com
plications.
Sedatives are commonly used to reduce the symptoms of al
cohol withdrawal and, if administered promptly, can prevent
progression to seizures and delirium tremens. Benzodiazepines
are usually the drugs of first choice. Longer-acting
drugs such as chlordiazepoxide or diazepam may be more
effective against withdrawal seizures and provide smoother
withdrawal while shorter-acting ones such as lorazepam or
oxazepam have a smaller risk of producing oversedation and
may be more suitable for use in the elderly, and, since they do
not rely on hepatic enzymes for their metabolism, for patients
with liver disease. Benzodiazepines should be given in short
courses only. to prevent the development of dependence.
Some advocate that benzodiazepine dosage should be adjust-
ed according io the severity of symptoms with special care
being paid to patients with a history of withdrawal seizures.
comorbid conditions, or those using sedative or hypnotic
medication. This reduces the amount of drug required and the
duration of treatment but entails regular monitoring by
trained nursing staff. For mild to moderate symptoms stand-
ard anxiolytic or muscle-relaxing oral doses of benzodi-
azepines may be sufficient. For severe symptoms or for the
treatment of delirium tremens higher doses and use of the in-
travenous route may be required. Chlornwthiawle appears to
be an effective alternative to the benzodiazepines but al-
though widely used in Europe it is not available in the US.
Some centrec use phenobarbitone but barbiturates are gener-
ally not recommended for the treatment of alcohol withdraw-
al syndrome.
Aittipsychotics are not usually recommended for use in the
control of symptoms of alcohol withdrawal since they do not
reduce delirium tremens and some may reduce the seizure
threshold. However, they might be considered for use as an
adjunct in patients requiring treatment of marked agitation or
hallucinations.
The generalised tonic-clonic seizures associated with alcohol
withdrawal are usually self-limiting and patients who experi-
ence only one or two seizures do not usually require any spe-
cific treatment beyond continuing therapy with
benzodiazepines orchlormethiazole. For recurrent seizures or
status epilepticus diazepam may be given intrave-
nously. Other types of seizure may be associated with head
trauma or pre-existing seizure disorders and should be
treated accordingly. Other antiepileptics such as car-
bamazepinc have been tried in the treatment of alcohol with-
drawal seizures and may be of use as adjuncts in controlling
other symptoms of alcohol withdrawal syndrome. As benzo-
diazepines are effective in preventing withdrawal seizures
other prophylactic drugs are not usually indicated.
Beta blockers can reduce symptoms of autonomic overactivi-
ty such as tachycardia, hypertension, tremor, and agitation but
because they can mask these symptoms of withdrawal and do
not prevent the development of more serious complications
they should not be used alone. Some beta blockers such as
propranolol which penetrate the CNS may produce CNS ef-
fects which complicate therapy. The alpharadrenergic recep-
tor agonist clonidine may be of similar benefit as an adjunct.
Other drugs that have been reported to be of benefit in alcohol
withdrawal syndrome include nitrous oxide and gamma-hy-
droxybutyric acid.
It is essential that in all cases of alcohol withdrawal syndrome
hypoglycaemia. dehydration, electrolyte disturbances (in par-
ticular magnesium), and vitamin deficiencies be corrected. It
is usually recommended that all patients should be given thi-
amine because of their increased risk of developing Wer-
nicke's encephalopathy.It should be noted that
intravenous administration of glucose solutions before thia-
mine may precipitate Wemicke's encephalopathy in thia-
mine-deficient patients. However, hydration shoulrf be
undertaken with care as alcoholics may be more prone to de-
velop cerebral oedema. The management of cerebral oedema
is discussed under Raised Intracranial Pressure on p.796.
Abstinence. Once the initial acute withdrawal of alcohol is
achieved treatment may be required to maintain long-term ab-
stinence. Pharmacotherapy should only be used as an adjunct
to psychotherapy and supportive care. Drugs used to modify
alcohol seeking behaviour either sensitise the patient to alco-
hol (aversive drugs) or reduce or alleviate the craving for al-
cohol. The main agents used for aversive therapy are
disulfiram and calcium carbimide. A patient who ingests al-
cohol after taking an adequate dose of one of these drugs will
experience a severe and unpleasant reaction (see p. 1573).
However, the deterrent value of aversive drugs, and their po-
tential toxicity, has long been a matter of debate. Such treat-
ment is likely to be of little use unless it is undertaken with the
willing cooperation of the patient and is used with psycho-
therapy and even then there is no evidence that it has any ef-
fect on the long-term course of alcoholism.
Of those drugs which have been reported to reduce alcohol
craving acamprosate and naltrexone have been the most
promising as adjuncts for management of alcohol dependence
and have been shown to improve abstinence and reduce re-
lapse rates. Whether benefit is maintained long-term after
treatment is stopped is unclear. Other drugs tried with varying
benefit include tiapride, selective serotonin reuptake inhibi-
tors. gammahydroxybutyric acid, and bromocriptine. Use of
antidepressants may improve outcome in patients with con-
comitant depression.
Precautions
Women and the elderly may be more susceptible to
the adverse effects of alcohol ingestion. Alcohol
may aggravate peptic ulcer or impaired liver func-
tion. Ingestion of alcohol during pregnancy or by
nursing mothers is not advisable. Excessive alcohol
intake should be avoided in patients with diabetes
mellitus or epilepsy. In chronic alcoholics there may
be tolerance to the effects of other CNS depressants
including general anaesthetics.
All processes requiring judgement and coordination
are affected by alcohol and these include the driving
of any form of transport and the operating of ma-
chinery. It is an offence in many countries for motor-
ists to drive when the blood-alcohol concentration is
above a 'stated value. The alcohol concentration in
urine and expired air can be used to estimate the
blood-alcohol concentration. .
It should be remembered that alcohol may be
present in a number of pharmaceutical preparations
such as elixirs and mouthwashes. and that children
may be particularly susceptible to its hypoglycae-
mic effects.
Porphyria. Alcohol has been associated with acute attacks of
porphyria and is considered unsafe in patients with acute por-
phyria.'
Interactions
Reports of interactions between alcohol and other
drugs are not consistent, possibly because acute al-
cohol intake may inhibit drug metabolism while
chronic alcohol intake may enhance the induction of
dnig-metabolising enzymes in the liver. Alcoholic
beverages containing tyramine may cause reactions
when taken by patients receiving MAOls. Alcohol
may enhance the acute effects of drugs which de-
press the central nervous system, such as hypnotics.
antihistamines. opioid analgesics, antiepileptics.
antidepressants, antipsychotics, and sedatives. Un-
pleasant reactions, similar to those occurring with
disulfiram. may occur when alcohol is
taken concomitantly with chlorpropamide. mepa-
crine, metronidazole and other nitroimidazoles, the
nitrofuran derivatives furazolidone and nifuratel,
procarbazine. and some cephalosporins.
Alcohol may cause hypoglycaemic reactions in pa-
tients receiving sulphonylurea antidiabetics or insu-
lin, and may cause orthostatic hypotension in
patients taking drugs with vasodilator action. It may
enhance the hypotensive effects of antihypertensives
and has also increased the sedative effect of indo-
ramin. Alcohol may increase gastric bleeding
caused by analgesics and may have a variable effect
on oral anticoagulants. It may decrease the antidiu-
retic effect of vasopressin.
Interactions involving alcohol have been reviewed.
The effects of paracetamol poisoning may be exacerbated by
prolonged alcohol use.
When taken concomitantly with alcohol verapamil has been
reported to cause an increase in peak blood-alcohol concen-
trations of approximately 17%. Such an interaction may ex-
tend the toxic effects of alcohol and raise its blood
concentration above the legal limit for drivings Increased
blood-alcohol concentrations have also been reported in pa-
tients receiving cycloserine. Alcohol has also been reported
to interact with nifedipine resulting in increased blood con-
centrations of nifedipine.
The existence of an interaction between H-2-receptor antago-
nists and alcohol is controversial and has not been estab-
lished. While some studies suggest that cimetidine and
nizatidine can increase peak blood concentrations of alco-
hol the effects of ranitidine have been variable.famotidine
appears to have no significant effect.g Recent studies report
that any interaction between H2-receptor antagonists and al-
cohol is minor and unlikely to be of clinical importance.
Pharmacokinetics
Alcohol is rapidly absorbed from the gastro-intesti-
nal tract and is distributed throughout the body flu-
ids. It readily crosses the placenta. Alcohol vapour
can be absorbed through the lungs. Absorption
through intact skin is said to be negligible.
The. rate of absorption of alcohol from the gastro-
intestinal tract may be modified by such factors as
the presence of food, the concentration of alcohol,
and the period of time during which it is ingested.
Some alcohol is reported to be metabolised by the
gastric inucosa.
Alcohol is mainly metabolised in the liver; it is con-
verted by alcohol dehydrogenase to acetaldehyde
and is then further oxidised to acetate. A hepatic mi-
crosomal oxidising system is also involved. About
90 to 98% of alcohol is oxidised and the remainder
is excreted unchanged by the kidneys and the lungs
and also in breast milk, sweat, and other secretions.
The rate of metabolism may be accelerated follow-
ing repeated excessive intake and by certain sub-
stances including insulin.
The pharmacokinetics of alcohol have been reviewed by Hoi-
ford.' A study by Frezza and others' showing that gastric ox-
idation of alcohol was reduced in women compared with men
leading to women having increased blood-alcohol concentra-
tions, stimulated considerable correspondence. Seitz et al.~
demonstrated that only women under the age of 50 years have
lower alcohol dehydrogenase activity than men, and that in
elderly women the activity was not significantly less than in
men. Phillips4 pointed out that acetaldehyde may be more
toxic than alcohol and that reduced first-pass metabolism in
women may lessen their risk of toxic liver effects. The study
by Frezza has aTso been criticised on pharmacokinetic
grounds' and on the basis that men and women display dif-
ferences in social drinking patterns' In reply Frezza et al*
refute some of these criticisms but point out that other factors,
such as sex-related differences in tissue vulnerability, may
contribute to differences in the severity of medical problems
related to drinking.
Uses and Administration
Alcohol has bactericidal activity and is used to dis-
infect skin prior to injection, venepuncture, or surgi-
cal procedures. It is also used to disinfect hands and
clean surfaces. A concentration of 70%, often as
methylated spirits, is commonly employed
for disinfection. Alcohol should not be used for dis-
infection of surgical or dental instruments because
of its low efficacy against bacterial spores.
Alcohol also has anhidrotic, rubefacieiU, and astrin-
gent and haemostatic properties. It is sometimes
used for its skin-cooling properties and to harden the
skin. It is an ingredient of several topical prepara-
tions used for skin disorders.
Alcohol is widely used as a solvent and preservative
in pharmaceutical preparations.
Alcohol may be used as a neurolytic in the manage-
ment of severe and chronic pain. Intrathecal injec-
tion of alcohol has also been used for the intractable
pain of spasticity.
Alcohol is given intravenously in the treatment of
acute poisoning from ethylene glycol and
methyl alcohol.
Alcohol is also used in sclerotherapy.
Disinfection. VIRUSES. Hanson et al. ' reported 70% alcohol to
be ineffective against HIV dried onto sterile glass coverslips
in the presence of 10% serum. However, de Jong and van
Klingeren2 pointed out that HIV in suspension was very sensitive
to 70% alcohol and that in practice, the poor penetrating
power of alcohol was compensated for by removal of visible
contamination from surfaces prior to disinfection. Another
study' showed that inactivation of dried HIV by 70% alcohol
was slow. especially in the presence of a high concentration
of protein, and that high litres of virus required a 2-minute full
immersion period m alcohol.
WHO has published guidelines on sterilisation and disinfec-
tion methods effective against HIV4 which state that alcohols
are not considered suitable for dealing with contaminated sur-
faces because of their limited penetration of organic residues
and rapid evaporation but that for disinfection of living tis-
sues, alcohol 70% is effective.
Pain. The nearolytic use of alcohol to produce destructive
nerve block has produced variable results, and some
consider the risk of complications outweighs the benefits.
However, alcohol has been injected into the pituitary gland
for relief of severe pain of the head and neck;doses of I mL
of absolute alcohol have been used. ' It may be useful in coe-
liac plexus block, and has been injected into the muscle
sheath to relieve painful muscle spasms in patients with mul-
tiple sclerosis.' Alcohol 50 to 100% may be used for periph-
eral or central nerve block in terminally ill patients with pain
that does not respond to drug therapy; the block produced by
alcohol may "ccasionally last up to 2 years, even longer than
that produced by phenol.
Prostatectomy. Intravascular absorption of irrigating solu-
lions during transurethral resection of the prostate can
be
monitored by measuring breath-alcohol concentrations re-
suiting from alcohol added to the solution before use.'
Sclerotherapy : Alcohol has been used successfully as a
sclerosant in a variety of conditions including aldostcrone-
producing adenoma,' parathyroid adenomas,* thyroid nod-
ule, advanced rectal cancer, hepatocellular carcinoma,
dysphagia associated with oesophogastric cancer, hepatic
cyst, and gallbladder obstruction. "It has also been used in
the sclerotherapy of oesophageal varices'~ although the
safety of this procedure has been qutestioned following a re-
port of complications developing in 13 of 17 patients. 2 of whom
died.
Other conditions in which alcohol has been used include bleeding from
ruptured hepatoma and from peptic ulcers and obstructive
cardiomyopathies resistant to usial treatment.