Synopsis of Important Principles
Medical Services
1. Specific antidotal therapy is available for very few poisons. The mainstay of treatment of severe poisoning is intensive supportive therapy and good nursing care.
2. The great majority of poisoned patients recover with intensive supportive therapy alone, and enthusiastic claims for the success of other treatment often cannot be justified.
3. With some important exceptions, the management of poisoning is not altered by knowledge of plasma drug concentrations. There are many pitfalls in the interpretation of drug concentrations in poisoned patients, especially when nonspecific analytical methods are used.
4. Gastric lavage and induction of nemesis soon after ingestion may be effective in removing unabsorbed drug, but are unreliable. Adsorbents such as activated charcoal are usually ineffective in limiting absorption when given more than 1 hour after ingestion.
5. Poisoned patients are often subjected to unnecessary and potentially harmful haemodialysis, haemoperfusion and diuresis. The efficacy of these measures has been established for relatively few substances in terms of reduction in morbidity and mortality or removal of toxicologically significant amounts of active drug or poison.
6. The efficacy of methods for extracorporeal removal can be predicted from pharmacokinetic principles. It depends primarily on the volume of drug distribution, plasma protein binding, rate of transfer from peripheral to central compartments, and dialysis clearance relative to the endogenous total body clearance.
7. Haemoperfusion with activated charcoal or exchange resins is more effective than haemodialysis in removing drugs from the blood. Peritoneal dialysis is less effective than haemodialysis. Drugs with large volumes of distribution cannot be removed rapidly by any of these techniques, and indications for their use are limited.
8. Forced diuresis can only increase the renal clearance of reabsorbed compounds, and clearance may be dramatically increased by appropriate manipulation of urine pH. However, the renal excretion of most drugs is insignificant in relation to the metabolic clearance. Forced alkaline diuresis is largely restricted to salicylate and phenobarbitone poisoning.
9. Repeated oral activated charcoal effectively increases the body clearance of a number of drugs. It probably acts by irreversibly binding drug diffusing from the circulation to the gut lumen and may also interrupt the enterohepatic circulation.
10. The toxicity of a few drugs and poisons can be reversed by specific antidotal therapy. Mechanisms include pharmacological antagonism, inhibition of conversion to toxic metabolites, inactivation of highly reactive alkylating intermediates, chelation and binding with drug-specific antibodies.
