Clinical Pharmacology and Therapeutics

446 DRUG OVERDOSE AND POISONING
appropriate resuscitation, repeated observations are necessary,
as drugs may continue to be absorbed with a subsequent
increase in plasma concentration. In the unconscious patient,
repeated measurements of cardiovascular function, including
blood pressure, urine output and (if possible) continuous electrocardiographic
(ECG) monitoring should be performed.
Plasma electrolytes and acid-base balance should be measured.
Hypotension is the most common cardiovascular complication
of poisoning. This is usually due to peripheral
vasodilatation, but may be secondary to myocardial depression
following, for example, α-blocker, tricyclic antidepressant
or dextropropoxyphine poisoning. Hypotension can usually be
managed with intravenous colloid. If this is inadequate, positive
inotropic agents (e.g. dobutamine) may be considered. If
dysrhythmias occur any hypoxia or hypokalaemia should be
corrected, but anti-dysrhythmic drugs should only be administered
in life-threatening situations. Since the underlying cardiac
tissue is usually healthy (unlike cardiac arrests following
myocardial infarction), prolonged external cardiopulmonary
resuscitation whilst the toxic drug is excreted is indicated.
Respiratory function is best monitored using blood gas analysis –
a PaCO 2 of 6.5 kPa is usually an indication for assisted ventilation.
Serial minute volume measurements or continuous
measurement of oxygen saturation using a pulse oximeter are
also helpful for monitoring deterioration or improvement in
self-ventilation. Oxygen is not a substitute for inadequate ventilation.
Respiratory stimulants increase mortality.
ENHANCEMENT OF ELIMINATION
Methods of increasing poison elimination are appropriate in
less than 5% of overdose cases. Repeated oral doses of activated
charcoal may enhance the elimination of a drug by ‘gastrointestinal
dialysis’. Several drugs are eliminated in the bile and
then reabsorbed in the small intestine. Activated charcoal can
interrupt this enterohepatic circulation by adsorbing drug in
the gut lumen, thereby preventing reabsorption and enhancing
faecal elimination. Cathartics, such as magnesium sulphate,
can accelerate the intestinal transit time, which facilitates the
process. Orally administered activated charcoal adsorbs drug in
the gut lumen and effectively leaches drug from the intestinal
circulation into the gut lumen down a diffusion gradient.
Although studies in volunteers have shown that this method
enhances the elimination of certain drugs, its effectiveness in
reducing morbidity in overdose is generally unproven.
However, it is extremely safe unless aspiration occurs. Forced
diuresis is hazardous, especially in the elderly, and is no longer
recommended. Adjustment of urinary pH is much more effective
than causing massive urine output. Alkaline diuresis (urinary
alkalinization) should be considered in cases of salicylate,
chlorpropramide, phenoxyacetate herbicides and phenobarbital
poisoning, and may be combined with repeated doses of oral
activated charcoal. Acid diuresis may theoretically accelerate
drug elimination in phencyclidine and amfetamine/ ’ecstasy’
poisoning. However, it is not usually necessary, may be harmful
and is almost never recommended.
Table 54.4:
elimination
Method
Alkaline diuresis
Haemodialysis
Methods and indications for enhancement of poison
Charcoal haemoperfusion
‘Gastro-intestinal dialysis’
via multiple-dose
activated charcoal
Haemodialysis and, much less commonly, charcoal haemoperfusion
are sometimes used to enhance drug elimination.
Table 54.4 summarizes the most important indications and
methods for such elimination techniques. In addition, exchange
transfusion has been successfully used in the treatment of poisoning
in young children and infants. The risk of an elimination
technique must be balanced against the possible benefit of
enhanced elimination.
SPECIFIC ANTIDOTES
Poison
Salicylates, phenobarbital
Salicylates, methanol, ethylene
glycol, lithium, phenobarbital
Barbiturates, theophylline,
disopyramide
Salicylates, theophylline, quinine,
most anticonvulsants, digoxin
Antidotes are available for a small number of poisons and the
most important of these, including chelating agents, are summarized
in Table 54.5.
NALOXONE
Naloxone is a pure opioid antagonist with no intrinsic agonist
activity (Chapter 25). It rapidly reverses the effects of opioid
drugs, including morphine, diamorphine, pethidine, dextropropoxyphene
and codeine. When injected intravenously,
naloxone acts within two minutes and its elimination half-life is
approximately one hour. The plasma half-life of most opioid
drugs is longer (e.g. 12–24 hours) and repeated doses or infusions
of naloxone may be required. The usual dose is
0.8–1.2 mg, although much higher doses may be needed after
massive opioid overdoses, which are common in addicts and
especially after a partial agonist (e.g. buprenorphine) overdose,
because partial agonists must occupy a relatively large fraction
of the receptors compared to full agonists in order to produce
even modest effects. Naloxone can precipitate withdrawal reactions
in narcotic addicts. This is not a contraindication, but it is
wise to ensure that patients are appropriately restrained if this
is a risk.
MANAGEMENT OF SPECIFIC OVERDOSES
PARACETAMOL
This over-the-counter mild analgesic is commonly taken in
overdose. Although remarkably safe in therapeutic doses,