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