Antidotes and their Clinical

Applications
Arnold Forkuo Donkor, PhD
Department of Pharmacology, KNUST.

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 Antidote
• An antidote is a substance that can counteract a form of poisoning. The
term antidote is a Greek word “Antididonai” meaning “given against”.
• According to WHO:
• “Antidote is defined as a therapeutic substance used to counteract the toxic
action(s) of a specified xenobiotic.”
• Antidotes generally reduce the overall burden of health service in managing
of poisoning cases.

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 Antidote
• Acutely poisoned patients are commonly encountered in Emergency
Centres.
• Acute poisoning (accidental or intentional) requires accurate assessment
and prompt therapy.
• Early identification of the involved toxin/s is crucial and the majority will
be identified by a thorough history and physical examination.
• Antidotes such as digoxin immune Fab can be lifesaving; however, an
antidote must be available at the appropriate time to be effective. For
some poisons, the antidote must be available immediately.

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 Antidote
• Antidotes are a critical component in the care of poisoned patients.

• For instance, the administration of cyanide antidote can resuscitate a patient only if the
antidote is administered before irreversible injury develops. For other antidotes, there is
time to procure the drug from a pharmacy or from another hospital.

• An ABC-approach should be followed ensuring a protected airway, adequate ventilation

and hemodynamic stability. Supportive and symptomatic care remains the cornerstone
of treatment.

Supportive correct Pt.Survival

therapy Antidote

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 Antidotes and supportive care
• Despite popular misconceptions, the administration of an antidote is
indicated in only the minority of poisoning cases.
• Basic supportive and symptomatic measures might be all that is needed
with the possible addition of gastric decontamination or methods to
increase elimination.
• The administration of an antidote must only be considered if the identity
of the toxin has been confirmed.
• The clinician should be aware of the specific indications and contra-
indications associated with the administration of the antidote.

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 Antidotes and supportive care
• A stepwise approach may be followed to decrease the bioavailability of
toxins.
• Staff should be aware of the necessity of taking universal measures to
prevent cross contamination during the initial evaluation, depending on
the nature of the poison (e.g. organophosphates, cyanide).
• Indications, contra-indications, risks and dosage regimens are describe
for decontamination procedures including both termination of topical
exposures and decreasing exposure to ingested toxins.
• The availability of certain antidotes remains a problem in the Ghanaian
public healthcare sector and in treating poisoned patients, physicians
should focus on providing optimal supportive care.
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Approach to the management of the poisoned patient
• Acute poisoning requires accurate assessment and prompt therapy.
All patients must be thoroughly assessed and stabilized from the
start.
• History attempts should be made to try to identify the specific poison
but this however must never delay life-saving supportive care.
• Therefore, while vital functions are being assessed and stabilized, a
proper history should be obtained. Important information to be
gained from the history for risk assessment includes
• the nature of the poisonous substance,
• the degree of exposure and
• the time since exposure.

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 POISONS
• Poisons, including medicines, may be divided into two broad categories:

i. Poisons (and/or their metabolites) which directly cause irreversible or

slowly reversible structural or functional damage to one or more organ
systems. These are also considered to be compounds with a high inherent
toxicity. Included in this category, are substances causing delayed
significant symptoms and signs (e.g. paracetamol).

ii. Poisons which do not cause tissue damage directly or those which cause
toxic effects that are rapidly and completely reversible. Fortunately, most
potential poisons fall in this category and appropriate symptomatic and
supportive care during the acute phase will usually ensure complete
recovery.
 POISONS
• When dealing with a suspected toxic exposure or poisoning, one of the major
priorities should be the attempt to identify agents with a high inherent toxicity as
soon as possible.
• Early identification will allow for timeous special decontamination and antidotal
procedures in order to avoid severe or permanent tissue damage.
• A history obtained from a poisoned patient is often unreliable. If possible,
relatives and friends should also be questioned as they may have useful
information as to what the poison was.
• A special effort should be made to obtain a sample of the poisonous substance
and its relevant container. A hospital personnel should be instructed to collect
these from the scene.
• Examination of the suspected toxic substance or the material ingested is crucial
for rapid and positive identification of a poison.
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 Classification of Antidotes
• According to mode of action:
• Mechanical

• Chemical

• Physiological/Pharmacological

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 Mechanical Antidote
• Mechanical antidotes which prevent the absorption of poison into the
body.
• Adsorbing: The main example is activated charcoal.
• Activated charcoal adsorbs the poison prior to absorption across the intestinal wall

• Coating: A mixture of egg and milk make a coat over the mucosa impairing
the absorption of the poison.

• Dissolving: 10% alcohol or glycine for carbolic acid

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 Chemical Antidote
• Chemical antidotes are the agents which interact specifically with toxicant changing
the chemical nature of poison.
• Examples:
• Sodium Thiosulphate changes toxic cyanide to the non-toxic thiocyanate-sodium:

• Sodium Calcium edetate chelate agents used for heavy metal poisoning.

• Metal chelators combine with metals to form complexes that can then be
eliminated by the kidneys.
• Chemical antidotes act by two mechanisms:
a)Complex formation b) metabolic conversion

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 Chemical Antidote
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 and lead.
• Specific binding agents like EDTA, deferoxamine and D-pencillamine
act by chelation of metal forming more water soluble complex.
• Antivenins and antibodies against digitoxin are immunologically
generated agents that bind specifically to the toxin or venom.

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 Chemical Antidote
Metabolic conversion
• Detoxification to less toxic product
• Nitrite interact with hemoglobin and cyanide to form
cyanmethamoglobin, which is less toxic than cyanide and interfere
with the cyanide access to cytochrome oxidase system.

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 Pharmacological antidote
• Counteract the effects of a poison by producing the opposite
pharmacological effects. e.g., ACHE inhibitors atropine.

• Pharmacologic antidotes antagonizes the effects of a toxicant.

• This type of antidote may act by the following mechanisms.

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 1. Competing with the toxicant’s action at a
receptor sites
a. Antagonism
Competitive antagonism
• Naloxone/Naltrexone: Opioid dependence, longer action and affinity for mu-
receptor.
• Flumazenil: Antagonist for Benzodiazepine
• Atropine: Organophosphate, carbamate and other parasympathomimetic
antidote.
It is also used to correct bradycardia caused by morphine, digitalis and beta
blockers.

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 1. Competing with the toxicant’s action at a receptor sites
Non Competitive Antagonism
• Calcium gluconate: Used for Calcium channel blocker especially Verapamil
• Black widow spider bite
• Lead colic
• Oxalic acid

Pralidoxime: ChE reactivator 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.
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 2. 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: supplies the precursor amino acids for glutathione,
which serves as biologic antioxidant against acetaminophen toxicity.

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 Antidote-Poison Reactions

• Cholinesterase reactivators (oximes) loses

effectiveness after a certain time ( after “ageing of
the cholinesterase-inhibitor complex)
• Organophosphates include insecticides (parathion,
malathion)and nerve gases (sarin, tabun, soman,
VX).
• Fomepizole is a potent inhibitor of alcohol
dehydrogenase.
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 Metal chelators

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 Mechanism of Action of Antidotes
1. Interacts with the poison to form a non-toxic complex that can be
excreted – chelators
2. Accelerates the detoxification/ promote return to normal function by
repairing a defect of the poison- N-acetylcystine, thiosulphate.
3. Decrease the rate of conversion of poison to toxic metabolites-
Ethanol and fomepizole
4. Compete with the poison for the same receptor sites- Naloxone
5. Blocks the receptor through which the toxic effect of the poison is
mediated- atropine.
6. Antibodies to the poison- digibind and antivenoms

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List of agents and their Antidotes
Drugs, Metals and Household compounds

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 Drugs and antidotes
Toxicant Antidote

Acetaminophen N-Acetylcycteine or methionine

Benzodiazipines Flumazenil

Coumarins Vitamin K

Digitalis (Cardiac glycosides) Digoxin-specific Fab fragments(Digibind)

Cyanide Hydroxocobalamin, Sodium thiosulphate, Na nitrite

Isoniazid (INH) or hydrazines Vitamin B6 (Pyridoxine)

Heparin Protamine sulphate

Theophylline Adenosine + Beta blocker

Penicillin Epinephrine

Morphine sulphate (Opioids) Naloxone hydrochloride

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 Drugs and antidotes
Warfarin Vitamin K

Salicylates Activated Charcoal

Sulphonylureas Glucose + octreotide

Muscarinic receptor blockers (Anticholinergics) Physostigmine or Neostigmine

Calcium channel blockers Calcium gluconate

Methanol, ethylene glycol Ethanol, Fomepizole

Insulin injection Glucose

Beta blockers Glucagon

Potassium Insulin and glucose

Organophosphates Atropine + Pralidoxime

Amphetamine Propranolol

Carbamate Atropine

MAOI Phentolamine
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 Metals and others
Mercury and Gold Penicillamine
Manganese Na2Ca-EDTA

Copper Penicillamine

Carbon monoxide Oxygen

Arsenic Dimercaprol

Lead Na2Ca-EDTA + Penicillamine

Magnesium sulphate Calcium gluconate

Iron and aluminium salts Deferoxamine (Desferrioximine)

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 Activated Charcoal(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 (1000 m2/g). The activation removes all the
oxygen through controlled oxidation and or steam processing.

• 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 a 40:1 ratio (by weight) of charcoal to drug.
•  Contraindicated for iron, lithium, potassium, acids/alkalis and ethanol
overdose.
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 How does activated charcoal work?
• Activated Charcoal works by adsorbing drugs and
poisons within the gastrointestinal tract. This allows
their transfer out of the body in a harmless form.
• It attracts other substances to its surface and hold on
them until they exit the body. Powdered charcoal
reaches its maximum rate of adsorption rapidly,
within 1 minute.
• It should be given within the first 30 minutes of an
overdose.

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 Milk
• Few poisons have specific antidotes. The most common substance that
is effective and generally available in the household is MILK.
• The Calcium and protein in milk serve as chelators for the ingested
poison.
• It coats the stomach mucosa, protecting and delaying absorption.

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 Common side effects of some Antidotes
• Charcoal (Common) • Dimercaprol SE
• Black stools (severe) • Common side effect
• Diarrhea (Less severe) • Weakness
• Vomiting ( Less severe) • headache
• Rare side effects • Fever (esp. in children)
• Stomach cramps • Pain at site of injection
• Swelling of the abdomen (less • Nausea and vomiting
severe)
 Cyanide Antidote SE
• Common side effect • Rare side effect
• Abnormal Heart rhythm (severe) • Increased risk of bleeding (severe)
• Abnormally low BP (severe) • Excessive sweating(less severe)
• Coma (severe) • Lethargy (less severe)
• Confusion(less severe) • Rapid breathing(less severe)
• Tachycardia(less severe)
• Headache (less severe)

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 ASSIGNMENT
A. Mention all antidotes in the Essential Medicine List of Ghana. Indicate the various drug
over dose these antidotes are used for.

B. List 5 problems facilities in Ghana face in procuring and using COMMON antidotes that
are available elsewhere. Consider the following
• regulatory and administrative requirements
• Time and geography
• Scientific, technical and economic consideration.

C. What is the role of the pharmacist in the use of antidotes?

Classify antidotes into the four categories below (depending on the urgency of clinical need)
• Immediate,
• within one hour,
• within four hours,
• not critically time dependent.
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 Role Of Pharmacist
• Management of poisoning
• Stocking antidotes in Pharmacies.
• Poison control center
• Information concerning poisons
• Antidotes management
• Provide prevention services
• Educate community, other health care professionals
• Organized database management

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