Antidotes: Its Mechanism and Therapeutic Uses

An antidote is an agent which counteracts a poison In the treatment of acute poisoning most patients require only supportive and symptomatic therapy. The active removal of poisons from the stomach: >by gastric lavage or >emesis induction >reduce the absorption.

Mechanism of Action of Antidotes

1) 2) 3) 4) Complex formation Metabolic conversion Prevention of toxic metabolite formation By changing the physio-chemical nature of toxicant 5) Promotes return to normal function by repairing a defect or enhancing a function that corrects the effects of poison.

Classification of Antidotes
1) Chemical Antidotes, change the chemical nature of poison; example: sodium thiosulphate which changes toxic cyanide to the non-toxic thiocyanate-sodium calcium edetate chelates agents used for heavy metal poison. 2) Physiological Antidotes, producing the effect opposite to that of poison: sodium nitrite converts hemoglobin into methemoglobin in order to bind cyanide. 3) Mechanical Antidotes, prevent the absorption of poison into the body. example: activated charcoal absorbs the poison prior to absorption across intestinal wall. Copper sulphate, magnesium sulphate and sodium monohydrogen phosphate inactivate and precipitate the toxic material as insoluble salts by chelation

drug
Paracetamol (acetaminophen) Anticoagulants, E.G., Warfarin

Antidotes
(N-acetylcysteine) (Vitamin K)

Opioids
Iron (and other heavy metals) Benzodiazepines Methanol Cyanide Calcium Channel Blockers (Verapamil, Diltiazem) Beta-Blockers Propranolol, Sotalol) Isoniazid Atropine

(Naloxone)
(Desferrioxamine, Deferasirox or Deferiprone) (Flumazenil) (Ethanol or Fomepizole) (Amyl Nitrite, NaNitrite & Na Thiosulfate) (Calcium Gluconate) (Calcium Gluconate and/or Glucagon) (Pyridoxine) (Physostigmine)

PARACETAMOL
Acetylcysteine (N-acetylcysteine) is used as a mucolytic and to treat paracetamol overdose. Acetylcysteine splits disulfide bonds in muco-proteins and thus lowers mucus Viscosity, resulting in a larger volume of sputum. Acetylcysteine is also an antioxidant andmay protect the lung from free radicals generated by inflammatory cells activated by influenza virus infection. Acetylcysteine is used intravenously as an antidote for severe paracetamol poisoning, in which it acts as a thiol donor

vitamin K
No clear mechanism of aldesleukin-induced coagulopathy has been identified, and the efficacy of prophylactic vitamin K has been disputed aldesleukin may activate the coagulation and fibrinolytic system

FLUMAZENIL
It binds selectively to a subset of Benzodiazepine receptors

NALOXON
naloxone, an effective opioid antidote Morphine reduces the rate of transient lower esophageal sphincter relaxation in patients with reflux disease, thus reducing the number of reflux episodes; the effect was reversed by naloxone