Clinical Pharmacology and Therapeutics

442 DRUGS AND ALCOHOL ABUSE
Interactions of alcohol with other drugs
Alcohol potentiates the effects of other CNS depressants (e.g.
benzodiazepines). Increased metabolism of warfarin and
phenytoin have been reported in alcoholics. Alcohol enhances
the gastric irritation caused by aspirin, indometacin and
other gastric irritants. Disulfiram-type reactions (flushing of
the face, tachycardia, sweating, breathlessness, vomiting and
hypotension) have been reported with metronidazole, chlorpropamide
and trichloroethylene (industrial exposure).
Enhanced hypoglycaemia may occur following coadministration
of alcohol with insulin and oral hypoglycaemic agents.
BARBITURATES
Thiopental is currently used i.v. to induce general anaesthesia
and to treat refractory status epilepticus. Earlier therapeutic
uses of barbiturates as hypnotics and anxiolytics are obsolete.
Tolerance with physical and psychological dependence
occurred after chronic administration. Central effects are similar
to alcohol. During withdrawal, convulsions are more often
seen in barbiturate-dependent patients than in those dependent
on alcohol. Barbiturate overdoses were commonly fatal
due to respiratory depression and/or asphyxia. Chloral
hydrate and clomethiazole have similar potential for dependence,
and their use is difficult to justify.
BENZODIAZEPINES
For more information on benzodiazepines, see Chapter 18.
SOLVENTS
Solvent abuse is common in adolescents. It is often part of more
widespread antisocial behaviour. A dependence syndrome has
not been identified. Solvents such as glues or paints are sniffed,
often with the aid of a plastic bag to increase the concentration of
vapour. The effect may be enhanced by reduced oxygen and
occur almost instantly (because of the rapid absorption of
volatile hydrocarbons from the lungs) and usually resolve within
30 minutes. Disinhibition can lead to excessively gregarious,
aggressive or emotional behaviour. Some sniffers just vomit.
Accidents are common; coma and asphyxiation occur. Cardiac
dysrhythmia can occur (as with hydrocarbon anaesthetics,
Chapter 24). Most deaths are associated with asphyxia as a result
of aerosol inhalations or bags placed over the head. Excessive
chronic use is rare, but may lead to major organ failure, as
well as permanent brain damage. There are no specific drug
therapies for solvent abusers and psychological and/or social
management is required.
MISCELLANEOUS
ANABOLIC STEROIDS
Anabolic steroids are abused by athletes in order to build up
muscle tissue. Most synthetic anabolic steroids are derived
from testosterone and are popular among body builders. The
prevalence of anabolic steroid abuse among athletes is uncertain.
It is likely that chronic use is associated with hypertension,
unusual hepatic and renal tumours, psychotic reactions and
depression on withdrawal, and possibly sudden death from
cardiac dysrhythmias. Other ‘performance-enhancing’ drugs,
usually of doubtful benefit but with side effects, include
human chorionic gonadotrophin, growth hormone, caffeine,
amphetamines, β-blockers and erythropoietin.
AMYL NITRATE AND BUTYL NITRATE
These inhaled drugs cause almost instant vasodilatation,
hypotension, tachycardia and a subjective ‘rush’. They are
claimed to enhance sexual pleasure and dilate the anus. The
hypotension can cause coma and frequent use of these drugs is
associated with methaemoglobinaemia. They work via cGMP,
so combination with sildenafil (Chapter 41) results predictably
in dangerously enhanced vasodilatation and hypotension.
GAMMA-HYDROXYBUTYRIC ACID (GHB)
GHB is a ‘popular’ drug of abuse whose effects may include
euphoria, sedation, amnesia (implicated as ‘date rape’ drug),
aggression, vomiting, coma, respiratory depression and seizure.
Management is supportive. Atropine may be required to treat
bradycardia.
Case history
A 70-year-old man is admitted with confusion, nystagmus
and ophthalmoplegia. His breath does not smell of alcohol.
Laboratory tests reveal a raised mean corpuscular volume
(MCV) and gamma-glutamyl transferase (GT), but are otherwise
unremarkable.
Question 1
What is the likely diagnosis?
Question 2
What does the initial treatment involve?
Answer 1
Wernicke’s encephalopathy.
Answer 2
Intravenous thiamine.
Case history
A 20-year-old man is brought by the police to the Accident
and Emergency Department unconscious. The police
believe that he ingested condoms full of diamorphine prior
to his arrest following a drugs raid. He had been in police
custody for approximately one hour. On examination he is
centrally cyanosed, breathing irregularly, with pinpoint
pupils and no response to painful stimuli. There is bruising
over many venepuncture sites.
Question 1
What is the immediate management?
Question 2
Abdominal radiography reveals six unbroken condoms in
the patient’s intestine. Is surgery indicated?
Answer 1
Give oxygen, maintain an airway and give intravenous
naloxone.
Answer 2
Since naloxone is an effective antidote to diamorphine poisoning,
close observation with repeated injections or infusion
of naloxone, inhaled oxygen and bulk laxatives should
be sufficient.