Antidote

Antidote

Prepared by: www.mcqsinpharmacology.com

Treatment of Poisoning:

Supportive care

Activated charcoal for serious oral poisonings

Occasional use of specific antidotes or dialysis

Only rare use of gastric emptying

• The proper use of antidotes in the intensive care setting, when combined with aggressive supportive care, may significantly reduce the morbidity and mortality associated with many severe poisonings.

www.mcqsinpharmacology.com

ANTIDOTES

• According to WHO“Antidote was defined as a therapeutic substance used to counteract the toxic action(s) of a specified xenobiotic.”

• antidotes reduce the overall burden of health service in managing of poisoning cases

Supportive therapy

correct

Antidote

Pt.Survival


CLASSIFICATION OF ANTIDOTE

• According to mode of Action:

Physical

Physiological/ Pharmacological

Chemical


According to Site of Action:1. Interacts with the poison to form a non toxic

complex that can be excreted:e.g. Chelators2. Accelrates the detoxification of the poison:e.g. N-

acetylcystine,thiosulfate3. Decrease the rate of conversion of posion into

toxic metabolite:e.g.Ethanol,Fomepizole4. Compete the poison for certain receptors.:e.g.

Nalaxone5. Block the receptor through which the toxic effect

of the poison is mediated e.g.Atropine6. Bypass the effect of Poison:O2 in the treatment

of CO and cyanide toxicity7. Antibodies to the poison : digiband and antivenoms

Physical Antidote:

Agent use to interfere with poison through physical properties, not change their nature

a) Adsorbing: The main example is activated charcol

b) Coating: A mixture of egg & milk make a coat over the mucosa.

c) Dissolving: 10% alcohol or glycine for carbolic acid


CHARCOL:(Universal Antidote)

• produced by heating pulverized carbonaceous substances sawdust, peat, or coconut shells

• activation: Hot air to erode the internal surfaces of the product and thereby increase its adsorptive surface area.

• Adsorption results from weak intermolecular (Van der Waals) forces

• AC can prevent systemic absorption of drugs when given within 1-2 h of ingestion

• The optimal dose is probably a 40:1 ratio (by weight) of charcoal to drug

• contraindicated for iron, lithium, potassium, and ethanol overdose

Chemical Antidote:

• Interact specifically with a toxicant, or neutralize the toxicant.

e.g. metal chelators combine with metals to form complexes that can then be eliminated by the kidneys

Mainly act by two mechanisms: Complex Formation:

Antidote make complex with the toxicant making it unavailable to cross the membrane or to interact with receptors DMSA(dimercaprol and dimercaptosuccinic acid

are sulfohydral compounds that bind metal such as arsenic acid ,lead.


Sp. Binding agents like EDTA, defroxamine and D-pencillamine act by chelation of metal forming more water soluble complex

Antivenins and antibodies against digitoxin are immunologicaly genrated agents that bind specifically to the toxin or venom

Metabolic conversion:

Detoxification to less toxic product

Nitrite interact with hemoglobin and cyanide to form cyanomethamoglobin , which is less toxic than cyanide and interfare with the cyanide access to cytochrome oxidase system.

Pharmacological antidote:• counteract the effects of a poison by producing the opposite

pharmacological effects, e.g., ACHE inhibitors atropine

• Pharmacologic antidotes may neutralize or antagonize the effects of a toxicant.

• This type of antidote may act by following 5 mechanism.


1. Preventing the formation of toxic metabolites:

More effective when given immediately before toxic metabolic activation

Example:

Ethanol and 4-methylpyrazole(4-MP) which compete with the alcohol dehydrogenase which prevent the formation of toxic intermediate from ethylene glycol.

2. By Facilitation Of More Rapid Or Complete

Elimination Of A Toxicant :

Change the physiochemical nature of toxin, allowing better glomerular filtration and prohibt tubular reabsorption.

eg., molybdenum and sulfate for copper toxicity by making water soluble complex,

3. By competing with the Toxicant’s action at a receptor site:

a) Antagonism:

Competitive antagonism: Naloxone/Naltrexone: Opioid dependence,

longer action and affinity for mu receptor.

Flumenazil: Antagonist for Benzodiazepine

Atropine: organophosphate, carbamate and other parasympathomimetic antidote.

It is also used to correct bradycardia caused by morphine, digitalis, beta blockers etc


Non Competitive Antagonism: Calcium gluconate:

Used for Calcium channel blocker especialy Verapamil Black widow spider bite Lead colic Oxalic acid

Paralidoxime :ChE activator act by breaking Alkyl phosphate ChE bond. It is used in organophosphate toxicity.

Diacetyl Monoxyime(DAM): action same as PAM but with more BBB penetration.

Physostigmine: Counteract the anticholinergic effect


4. By blocking receptors responsible for the toxic effect :

The physiologic effect induced by a toxin is prevented by an antidote, although the toxicant is unchanged and may still be active.

Example:

atropine blocks the physiologic effect of acetylcholine at cholinergic synapse and neuromuscular junction ,and in organophosphate toxicity


5. By aiding in the restoration of normal function:

The antidote promotes return to normal function by repairing a defect or enhancing a function that correct the effect of poison.

Example:

Methylene blue:

In nitrite poisoning, methylene blue interact with reduced NADPH to reduce the ferric iron of methemoglobin back to ferrous ion in hemoglobin, which can again transport oxygen

Acetylcysteine :

Acetylcysteien supplies the precursor amino acids for glutathione, which serves as biologic antioxident against acetaminphen toxicosis


ThanksQuestions ??


References:• http://

www.merckmanuals.com/professional/injuries_poisoning/poisoning/general_principles_of_poisoning.html

• J Med Toxicol. 2010 June; 6(2): 190–198. Activated Charcoal for Acute Poisoning: One Toxicologist’s Journey Kent R. Olson

• http://www.mdpoison.com/healthcareprofessionals/toxtidbits.html

• NVMS Toxiology by Grey D. Osweiller


http://www.merckmanuals.com/professional/injuries_poisoning/poisoning/general_principles_of_poisoning.html




http://www.ncbi.nlm.nih.gov/pubmed/?term=Olson%20KR%5Bauth%5D



http://www.mdpoison.com/healthcareprofessionals/toxtidbits.html



Antidote

Health & Medicine

Transcript of Antidote