Tiêu đề 2. ANTIDOTES AND THE CLINICAL APPLICATIONS.pdf ✅

PHARMD GURU Page 1  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. MECHANISM OF ACTIONS: Antidotes work in any one of a number of ways. Common modes of action are as follows: 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 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. 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). ANTIDOTES AND THE CLINICAL APPLICATIONS
PHARMD GURU Page 2 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. 5. RECEPTOR SITE BLOCKADE: This mode of action is best exemplified by atropine which blocks the effects of anti- cholinesterase 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. A list of antidotes recommended in poisoning: POISON ANTIDOTE Acetaminophen / Paracetamol Acetylcysteine Anesthetics, local Lipid emulsion (Fat Emulsion) Aniline Methylene blue Anticholinesterases (i.e. organophosphates) Atropine, Pralidoxime (2-PAM) Antidepressants, Cyclic (TCAs) Sodium bicarbonate, Lipid emulsion Antidepressants, noncyclic (i.e., SSRI’s, SNRI’s, bupropion, venlafaxine, etc) Sodium bicarbonate. Lipid emulsion Arsenic Dimaval Benzodiazepines Flumazenil Beta-blockers Atropine, Insulin, Calcium, Glucagon (adjunctive therapy only), Lipid emulsion Black Widow spider Black Widow spider antivenin (Antivenin Latrodectus Mactans) Calcium channel blockers Atropine, Insulin, Calcium, Lipid emulsion Cyanide Hydroxocobalamin (Cyanokit), Sodium thiosulfate
PHARMD GURU Page 3 Digoxin Atropine, Digoxin immune Fab Ethylene glycol Fomepizole, Pyridoxine, Sodium bicarbonate Glycol Ethers Fomepizole Hydrofluoric acid burns Calcium gluconate Iron Deferoxamine (Desferrioxamine) lsoniazid Pyridoxine Lead Dimaval Mercury (inorganic or elemental) Dimaval Methanol Fomepizole Mushrooms, Hepatotoxic (i.e., Amanita phalloides) Acetylcysteine Mushrooms, Seizure-inducing (gyromitra or hydrazine-containing mushrooms) Pyridoxine Nitrates Methylene blue Nitrites Methylene blue Opioids Naloxone Organophosphate insecticides Atropine Pralidoxime (2-PAM) Salicylates Sodium bicarbonate Sodium channel blocking drugs* (wide QRS) Sodium bicarbonate, Lipid emulsion Sulfonylurea (oral hypoglycemic) Octreotide ADJUVANT ANTIDOTES: AGENT INDICATION Benztropine Dystonia Chlorpromazine Psychotic states Corticosteroids Acute allergic reaction, laryngeal oedema Diazepam Convulsions Diphenhydramine Dystonia
PHARMD GURU Page 4 Dopamine Myocardial depression, vascular relaxation Epinephrine Anaphylactic shock, cardiac arrest Glucose Hypoglycaemia Lidocaine Ventricular arrhythmias OBSELETE ANTIDOTES: Unfortunately in India and other developing countries, cumbersome governmental regulations and a lack of economic incentives for manufacturers have restricted availability of a substantial number of new 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. Examples: OBSELETE ANTIDOTE INDICATION POISONING Copper sulfate Phosphorus Cysteamine Paracetamol Diethyl-dithio-carbonate Thallium Nalorphine Opiates tocopherol Paraquat 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.