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