Administration of antidotes, clinical toxicology

1. ANTIDOTES
T.SOUJANYA
16DC1T0021
PHARM. D

2. DEFINITION:
According to WHO, an antidote is defined as a therapeutic substance
used to counteract the toxic actions of a specified xenobiotic. Antidotes
reduce the overall burden of health service in managing of poisoning
cases.
The term antidote is a Greek word “Antididonai” meaning “given
against”. In Cambridge dictionary, antidote is defined as a chemical
especially a drug that limits the effects of a poison or a way of
preventing or acting against something bad
Poison + antidote = destroy poisoning

3. CLASSIFICATION OF ANTIDOTES:
According to mode of action, they are classified as follows:
1. Physiological/pharmacological antidote
2. Physical antidote
3. Chemical antidote

4. 1. PHYSIOLOGICAL/PHARMACOLOGICAL
ANTIDOTE:
It counteracts the effects of a poison by producing the opposite pharmacological
effects.
e.g. ACHE inhibitor - morphine
Pharmacological antidotes may neutralize or antagonize the effects of a toxicant.
This type of antidote may act by following 5 mechanisms:
• Preventing the formation of toxic metabolites.
• By facilitation of more rapid or complete elimination of a toxicant.
• By competing with the toxicant’s action at a receptor site.
• By blocking receptors responsible for the toxic effect.
• By aiding in the restoration of normal function.

5. 2. PHYSICALANTIDOTE:
The agent which is used to interfere with poison through physical
properties, not change their nature is known as physical antidote.
a) Adsorbing: Adsorption is the adhesion of atoms, ions or molecules
from a gas, liquid or dissolved solid to a surface. This process
creates a film of the adsorbate on the surface of the adsorbent.
e.g. Activated charcoal (Universal antidote)
a) Coating: A mixture of egg and milk make a coat over the mucosa.
b) Dissolving: 10% alcohol or glycerine for carbolic acid.

6. 3. CHEMICALANTIDOTE:
It interacts 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.
It mainly act by 2 mechanisms:
i) Complex formation.
ii) Metabolic conversion.

7. Contd...
i) Complex formation:
Antidote make complex with the toxicant making it unavailable to
cross the membrane or to interact with the receptors.
e.g. DMSA (dimercaprol and dimercaptosuccinic acid are sulfhydryl
compounds that bind metals such as arsenic acid, lead).

8. Contd...
ii) Metabolic conversion:
Detoxification to less toxic product:
Nitrate interact with haemoglobin and cyanide to form
cyanomethaemoglobin, which is less toxic than cyanide and interfere
with the cyanide access to cytochrome oxidase system.
Nitrate + oxyhaemoglobin methaemoglobin
+
cyanide
cyanomethaemoglobin

9. ANTIDOTE ADMINISTRATION:
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.

10. 1. INERT COMPLEX FORMATION:
Some antidotes interact with the poison to form an inert complex
which is then excreted from the body.
e.g. a) Chelating agents for heavy metals.
b) Prussian blue for thallium.
c) Specific antibody fragments for digoxin.
d) Dicobalt edetate for cyanide etc.

11. 2. ACCELERATED DETOXIFICATION:
Some antidotes accelerate the detoxification of a poison.
e.g. Acetyl cysteine acts as a glutathione substitute which combines with
hepatotoxic paracetamol metabolites and detoxifies them.
Thiosulfate accelerates the conversion of cyanide to nontoxic
thiocyanate.
Cyanide thiosulfate thiocyanate (detoxification)
(toxic) (antidote) (nontoxic)

12. 3. REDUCED TOXIC CONVERSION:
Antidote reduce the conversion of toxic product.
e.g. Ethanol which inhibits the metabolism of methanol to toxic metabolites
by competing for the same enzyme (alcohol dehydrogenase).
methanol
alcohol dehydrogenase
formaldehyde
alcohol dehydrogenase
formic acid
folate
Co2 and H2O

13. 4. RECEPTOR SITE COMPETITION:
Some antidotes displace the poison from specific receptor sites,
thereby antagonizing the effects completely.
e.g. Naloxone which antagonizes the effects of opioids at stereo-specific
opioid receptor sites.

14. 5. RECEPTOR SITE BLOCKADE:
Antidote binds to the receptor site of poison and block its action.
e.g. This mode of action is best exemplified by atropine which blocks
the effects of anticholinesterase agents such as organophosphates at
muscarinic receptor sites.

15. 6. TOXIC EFFECT BYPASS:
Antidote bypasses the toxic effect of poison.
e.g. Use of 100% oxygen in cyanide poisoning.

16. REFERENCES/BIBLIOGRAPHY:
1. A text book of modern medical toxicology by V.V. Pillay.
2. www.slideshare.net