Once the toxin has reached the biological receptor it is very difficult to provide any further specific treatment other than supportive care. The one exception to this statement is use of antidotes when available. This term is understood to mean a medicinal intervention that is specific to a toxin and is effective only for that toxin or others closely related to it. The term is sometimes used loosely when applied to a substance that acts indirectly and weakly on the mechanism of some toxin. Some would prefer defining an antidote as any substance that raises the lethal dose of a toxin. This is a looser definition which does not require that the antidote be specific in any manner.
An antidote might appear to be the ideal treatment for poisoning. It sometimes is. However, no antidote is completely without side effects. Many are only semi-specific. All must be given in a timely manner. In view of the many conditions relating to the administration of antidotes, it is perhaps not surprising that they are given with relative infrequency. According to the American Association of Poison Control Centers (AAPCC), antidotes were employed in only 0.9% (16,536 times among 1,713,462 cases) of the poisoning incidents about which they were contacted in 1990. The frequency of use rose to 1.3% of cases by 1993. The ten antidotes used most frequently are as follows:
It is useful to subdivide antidotes into four classes: chemical, receptor, dispositional, and functional. Chemical antidotes react with the poison, resulting in formation of a compound with lesser toxicity or reduced absorbability. An example is calcium chloride for oxalic acid poisoning. This antidote forms calcium oxalate when it reacts with oxalic acid and the calcium oxalate has low solubility which effectively limits its toxicity. Metal chelating agents are also examples of this type of antidote. Receptor antidotes compete with the poison for receptor sites. Naloxone, for example, reverses opiate-induced respiratory depression by binding to receptors and, thus, displaces the opiate from the receptor. Physostigmine also belongs to this category, in a manner of speaking. It inhibits the activity of cholinesterase. This action limits the poisonous effects of atropine and other anti-cholinergic compounds, which extends the activity of cholinesterase to harmful limits.
Dispositional antidotes reduce the amount of toxin available to tissues. They can do this in various ways including altering absorption, metabolism, distribution, or excretion of toxic agents. Acetaminophen is potentially extremely toxic and exerts its detrimental action by forming a toxic metabolite. The antidote, N-acetylcysteine, a dispositional antidote, limits the supply of this toxic metabolite by converting it to a nontoxic form.
Functional antidotes are antagonists. They have no direct action on the toxin itself nor on its action. However, they act on one biochemical system to offset the actions of a second biochemical system, the latter being the one affected by the toxin. As an example, the toxicity of many drugs or insect stings includes an immunological reaction which can reach anaphylactic proportions as the victim experiences severe breathing difficulties from bronchoconstriction. Epinephrine can reverse this by causing bronchial dilation with the restoration of normal breathing.
The Poison Control Centers include the compounds listed below among their clinically useful antidotes. They are mentioned briefly here and discussed in greater depth in the relevant portions of this text.
Amyl nitrate Cyanide
Antivenin Snake venom
Calcium EDTA Lead
Calcium Hydrofluoric acid gluconate
Digoxin Digitalis and other cardiac glycosides immune Fab
Dimercaprol Arsenic, some other metals
Ethanol Methanol, toxic alcohols
Glucagon Calcium channel
Methylene Blue Methemoglobin inducers
D-penicillamine Arsenic, other metals
Physostigmine Atropine, anticholinergics
Pyridoxine Isoniazid, some mushrooms
Succimer Lead, arsenic, mercury
Must be given < 24 hours post-ingestion;
activated charcoal absorbs antidote Provide immediately; converts hemoglobin to methemoglobin which becomes cyanide sink Polyvalent antiserum raised against common rattlesnakes; binds venom in vivo
Causes anticholinergic activation which counters cholinergic activity of insecticide Chelating agent
Forms insoluble, non-absorbable fluorides
Very high affinity for iron; discontinue therapy when urine color returns to normal
Chelating agent; reacts with adjacent sulfhydryls Competitive inhibitor of metabolizing enzyme Receptor antagonist Some activity with beta blockers and hypoglycemic agents A form of folic acid Stimulates alternative oxidative pathway Receptor antagonist Chelator
Acts on the neurotransmission by acetylcholine at the synapse agents
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