Antidotes and its clinical application

toxicology general principals of poisoning

1. Antidotes and its clinical application Presented to:- Mr. ARINJAY JAIN Presented by:- MOHD. FARHAN SHEHZAD (TPH1812003) KRITI JAIN (TPH1812004)

2. Antidotes An antidote is a substance which can counteract a form of poisoning. The term ultimately derives from the Greek “ pharmakon antidoton”medicine given as a remedy. In the majority of cases of acute poisoning, all that is required is intensive supportive therapy. Specific antidotes are rarely necessary, besides the fact that only a few genuine antidotes exist in actual practice , though there is no denying the dramatic results that can be achieved with some of them in appropriate circumstances . Proper antidotal therapy can be life-saving in some situations.

3. Mechanisms of action Antidotes work in any one of a number of ways. Common modes of action are as follows: 1 . Inert complex formation 2. Accelerated detoxification 3. Reduced toxic conversion 4. Receptor site competition 5. Receptor site blockade 6. Toxic effect bypass

4. 1 . Inert complex formation Some antidotes interact with the poison to form an inert complex which is then excreted from the body, e.g. chelating agents for heavy metals, Prussian Blue for thallium, specific antibody fragments for digoxin , dicobalt edetate for cyanide, etc.

5. 2 . Accelerated detoxification Some antidotes accelerate the detoxification of a poison, e.g. thiosulfate accelerates the conversion of cyanide to nontoxic thiocyanate , acetylcysteine acts as a glutathione substitute which combines with hepatotoxic paracetamol metabolites and detoxifies them.

6. 3 . Reduced toxic conversion The best example of this mode of action is provided by ethanol which inhibits the metabolism of methanol to toxic metabolites by competing for the same enzyme (alcohol dehydrogenase ).

7. 4 . Receptor site competition Some antidotes displace the poison from specific receptor sites, thereby antagonising the effects completely. The best example is provided by naloxone , which antagonises the effects of opiates at stereo-specific opioid receptor sites

8. 5 . Receptor site blockade This mode of action is best exemplified by atropine which blocks the effects of anticholinesterase agents such as organophosphates at muscarinic receptor sites. 6 . Toxic effect bypass An example of this type of antidotal action is provided by the use of 100% oxygen in cyanide poisoning .

9. Poison Antidote Acetaminophen / paracetamol Acetylcysteine Anesthetics, local lipid emulsion Aniline Methylene blue Anticholinesterases (organophosphates) atropine, pralidoxime Antidepressants ,cyclic (TCAs) Sodium bicarbonate Antidepressants, noncyclic Sodium bicarbonate Arsenic Dimaval Benzodiazepines Flumazenil Beta blockers Atropine, inuslin , calcium, glucagon Black widow spider Black widow spider antivenin Calcium channel blockers Atropine, insulin, calcium, Cyanide Hydroxocobalamin Digoxin Atropine , digosin immune fat Ethylene glycol pyridoxine, sodium bicarbonate

10. Poison Antidote Glycol ethers fomepizole Hydrofluronic acid burns Calcium gluconate Iroon Deferoxamine Isoniazid Pyridoxine Lead Dimaval Mercury Dimaval Methanol Fomepizole Mushrooms, hepatotoxic Acetylcysteine Mushrooms, seizure-inducing Pyridoxine Nitrates Methylene blue Nitrites Methylene blue Opioids Naloxene Organophosphate insecticides Atropine pralidoxime salicylates Sodium bicarbonate

11. Adjuvant antibiotics Agent Indications Benzatropine Dystonia Chlorpromazine Psychotic states Corticosteroids Acute allergic recation Diazepam Convulsions Diphenhydramine Dystonia Dopamine Myocardial depressions, vascular relaxation Epinephrine Anaphylactic shock, cardiac arrest Glucose Hypogycaemia Lidocaine Ventricular arrhythmias

12. Obselete antidotes Unfortunately in India, cumbersome governmental regulations and a lack of economic incentives for manufacturers have restricted availability of a substantial number of these life-saving drugs . As a result, doctors still use some substances which are more readily available as antidotes, but are generally considered obsolete or even dangerous in Western countries .

13. Agent Indication Copper sulfate Phosphorus Cysteamine Paracetamol Diethyldithiocarbamate Thallium Fructose Ethanol Levallorphan Opiates Nalorphine Opiates Silibinin Amanitin Tocopherol Paraquat Universal antidotes Ingested poison

14. Role of antidote in poisoning Antidotes may play an important role in the treatment of poisoning. While good supportive care and elimination techniques may, in many cases, restore a poisoned patient to good health and stabilize his or her body functions, the appropriate use of antidotes and other agents may greatly enhance elimination and counteract the toxic actions of the poison In certain circumstances they may significantly reduce the medical resources otherwise needed to treat a patient shorten the period of therapy, and, in some cases, save a patient from death. Thus antidotes may sometimes reduce the overall burden on the health service of managing cases of poisoning. In areas remote from good hospital services, and particularly in developing countries that lack adequate facilities for supportive care, antidotes may be even more essential in the treatment of poisoning

15. In poisoning, emetics or the stomach pump are indicated if the poison has not yet been absorbed, and where other less severe means are not effective . In order to produce vomiting warm water may be given, or, if necessary, a tablespoonful of mustard stirred to creamy consistency with water, this to be followed by large draughts of water. Generally this is later followed by demulcent drinks, such as flaxseed, whites of eggs beaten tip in water. slippery elm, etc. No emetics should be given, however, in poisoning by acetic, hydrochloric or muriatic, nitric and sulphuric acid.

16. Universal antidote A mixture of 50% activated charcoal, 25% magnesium oxide, and 25% tannic acid, formerly thought to be useful as an antidote for most types of acid, heavy metal, alkaloid, and glycoside poisons . It is now believed that the mixture is no more effective than activated charcoal given with water . The chemical nature of amorphous carbon combined with a high surface area and porosity makes it an ideal medium for the adsorption of organic chemicals . Activated charcoal is administered orally and functions by adsorbing molecules of complex organic compounds, thereby preventing the absorption of the potential toxicant from the GI tract and sequestering it to be eliminated in the feces .

17. Activated charcoal is normally used as an oral adjunct to more direct antidotal therapy during treatment of poisoning in animals. Animals showing signs of acute intoxication should be treated with a more specific antidote initially. In many cases there will not be a specific antidote and preventative measures such as gastric protection and antibiotics may be needed. Activated charcoal should not be given simultaneously or shortly before the oral administration of other therapeutic agents such Prepared by the Veterinary Technical Service Department of LLOYD, Inc.. Shenandoah, lowa as antibiotics, vitamins or amino acids. Antibiotic therapy should be administered parenterally when activated charcoal is used. Fluids to correct acid/base, hydration and electrolyte imbalances should be administered.

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