Antidotes and Their Mode of Action

Introduction

Antidotes can counteract or neutralize the effect of toxins and poisons. They can be administered intravenously (through the vein) or through the skin and mouth. Antidotes act by inactivating the poison, blocking its action, preventing its absorption, and neutralizing its effect. Antidotes can also reduce the toxic effects of poisons on different organs in the body. Toxic effects of toxins and poisons on body tissues and organs are reduced by toxic receptor blockage, competitive inhibition of receptors, and opposing its action. Antidotes can significantly reduce mortality and morbidity due to toxic chemical poisoning, but they are not available for all toxic agents.

What Are Antidotes?

An antidote is a chemical, drug, or chelating substance that can neutralize or counteract the effects of poison or a drug in the human body. They can have chemical, pharmacological, or physiological effects on the body. Antidotes reduce the toxicity of poisons and drugs by neutralizing the poison, reducing its action on organs, and preventing the absorption and conversion of toxins into toxic metabolites.

Based on the mode of action, they can be of three types.

• Physical Antidote - This type of antidote reduces the toxic effects of poison by physical properties like coating (applying covering (substrate) over the surface of any object), adsorption (capabilities of a solid substance to attract solutions or gases to their surface which are in contact with them), and dissolution (destruction or termination by breakdown).

• Chemical Antidote - It can reduce the toxic effects by changing the chemical properties of the poison.

• Pharmacological Antidote - This type of antidote will neutralize and oppose the pharmacological action of the poison.

How Do Antidotes Work?

The harmful effect of poisons and toxic chemicals in the body depends on various factors. It includes dose, route of administration, type of the toxin, and duration of exposure to the toxin. Antidotes can be again classified based on the mechanism of action. Antidotes reduce toxicity based on four essential functions. It includes:

• Reducing the Toxin Level - Antidotes act directly on the toxin or drug to reduce its concentration in the body. It includes increased elimination of the toxin and specific and nonspecific binding. Specific binding involves immunotherapy (type of cancer treatment), chelation (helps in reducing toxic effects of metals), and bio-scavenger therapy (natural proteins that can cause effective elimination of nerve agents). Antidotes bind with the toxic substances in specific binding and form inert complexes that are least reactive and eventually eliminated from the body. Nonspecific antidotes reduce the toxin levels by preventing absorption in the gastrointestinal tract. Nonspecific antidotes like activated charcoal (universal antidote) will adsorb the toxins and reduce their systemic absorption. Nonspecific antidotes will also interrupt the enterohepatic recirculation of toxic substances and reduce their concentration in the body.

• Blocking the Action Site of the Toxin - It is achieved by altering the toxin's receptor site or by modifying enzyme activity. Ethyl alcohol, used for methyl alcohol poisoning, competes with methyl alcohol molecules for alcohol dehydrogenase and reduces toxic metabolites. Antidotes like oximes used for organophosphorus poisoning work on the principle of enzyme reactivation.

• Reducing the Level of Toxic Metabolites - Antidotes can reduce the toxic effects of poisons by neutralizing the toxic metabolites or converting them into less toxic forms. N-acetyl cysteine used for Paracetamol poisoning converts the toxic metabolites into another form and thus reduces hepatic toxicity. Sodium thiosulphate used for cyanide poisoning converts toxic metabolites to less toxic substances and reduces the toxic effects.

• Counteracting the Harmful Effects of Toxins - Antidotes can reduce the toxic effects by directly inhibiting or reducing the effect of toxins. Atropine used for organophosphorus poisoning reduces the muscarinic effects of the poison and thus decreases the toxic effects on the body tissues. Vitamin K, used for Warfarin toxicity; folinic acid, used for Methotrexate overdose; and Pyridoxine, used for Isoniazid (INH) overdose, work on this principle.

When Should the Antidote Be Administered to a Person?

It is difficult to give guidance about administering an antidote in an emergency as it is usually based on the lag time to presentation, mechanism of action, and toxicokinetic properties of the antidote. Therefore, the maximum benefits of an antidote are uncertain and time-dependent.

Generally, the antidotes decrease toxin levels by either absorption or adsorption at the enzyme or receptor levels and are effective if administered early. Those antidotes modulate the effects or modify the toxic metabolites and could be given at variable times.

What Are the Common Drugs and Their Antidotes?

• Activated charcoal (universal antidote) is used for most oral toxins or nonspecific poisons.

• Calcium chloride is used for black widow spider bite poisoning.

• Acetylcysteine is used for Acetaminophen and Paracetamol poisoning.

• Flumazenil is used for Benzodiazepine overdose.

• Naloxone is used for opioid poisoning.

• Atropine sulfate is used for carbamate and organophosphate poisoning.

• Dimercaprol is used for inorganic mercury, gold, and arsenic toxicity.

• Methylene blue is used for drug-induced methemoglobinemia.

• Digoxin immune fab is used for Digoxin toxicity.

• Pralidoxime is used for anti-cholinesterase poisoning.

• Calcium salts are used for fluoride toxicity.

• Heparin is used for Ergotamine toxicity.

• Snake antivenom is used for cobra bites.

• Sodium thiosulfate for cyanide toxicity.

• Vitamin C for mercury toxicity.

• Thiamine (vitamin B1) is used to reduce the toxicity caused by alcohol poisoning.

• Sodium bicarbonate for poisoning due to chlorine gas inhalation.

• Protamine sulfate is used for Heparin toxicity.

• Penicillamine is used for arsenic, gold, lead, zinc, and copper toxicity.

• Mesna is used for Cyclophosphamide toxicity.

• Deferoxamine is used for toxicity due to iron.

• Beta-blockers for Theophylline toxicity.

• Persian blue can be used for Thallium toxicity.

• Intralipids are used for toxicity due to local anesthetic agents.

• Hyperbaric Oxygen Therapy (HBOT) for carbon monoxide and Cyanide poisoning.

• Fresh frozen plasma and vitamin K (phytomenadione) for toxicity due to Warfarin overdose.

• Chelators like Ethylenediaminetetraacetic acid (EDTA) and Dimercaptosuccinic Acid (DMSA) for toxicity due to heavy metal poisoning.

• Cyproheptadine for toxicity due to serotonin drugs (serotonin syndrome).

• Benztropine (INN) and Diphenhydramine hydrochloride (DPH) are used to reduce the extrapyramidal reactions caused by antipsychotic drugs.

• Octreotide for toxicity due to oral hypoglycemic (low blood glucose levels) drugs.

• Calcium gluconate is used for toxicity due to calcium channel blocker drugs and burns due to hydrofluoric acid (hydrogen fluoride and water).

• Five percent acetic acid (vinegar) for toxicity due to ammonia and urea.

• Yohimbine or Atipamezole for Amitraz toxicity.

• Pamidronate sodium or bisphosphonate for Cholecalciferol toxicity.

• 4-Methylpyrazole or Ethanol for toxicity due to Ethylene glycol.

Conclusion

Antidotes help to prevent and reduce the toxic effects of drugs and poisons. They may act by neutralizing the toxin, decreasing the absorption, preventing the conversion to toxic metabolites, and reducing the effect of toxins on organs. Proper use of antidotes and supportive medical management will reduce the dangerous adverse effects of toxins and help to reduce morbidity and mortality. The toxin must be appropriately diagnosed and confirmed before using the antidote.