Antidotes

Definition:
A therapeutic substance used to counteract
the toxic action(s) of a specified xenobiotic

Role of antidotes in Poisoning

Save the patient from death

Shorten hospital stay
Reduce the burden on health services
Especially important in developing
countries where adequate facilities may not
be available at the primary care level

WHO/IPCS Classification of
antidotes
Category A : Required to be immediately
available (within 30 minutes)
Examples are; Cyanide antidotes
Methylene blue
Naloxone
Ethanol

Category B: (Required to be
available within 2 hours)
Examples: Deferoxamine
N-acetyl cysteine
Flumazenil
Pralidoxime (2-PAM)

Category C : Required to available

within 6 hours
Examples:
Ca EDTA
Penicillamine
Vitamin K1
Succimer (DMSA)
Unithiol (DMPS)

Mechanism of action of antidotes

1. Physical action: e.g. activated charcoal
2. Chemical action:
Neutralization: acid and alkali
Chelation: metals and chelating agents
3. Antagonistic action: non-specific action e.g.
diazepam acts as an anticonvulsant for
convulsions due to any cause

Mechanism of action of antidotes

4. Competitive antagonism: ethanol competes
with methanol for the enzyme alcohol
dehydrogenase
5. Receptor antagonism: Atropine is antagonist
for acetyl choline at muscarinic receptors
6. Antigen antibody reaction: Digoxin specific
antibodies

Agents used to prevent absorption of poisons,

enhance elimination or treat symptomatically
Agents which prevent absorption of poisons
into the GI tract:
Activated Charcoal
Starch
Emetics:
Syrup of Ipecac

Cathartics and solutions for whole gut lavage

Magnesium citrate/sulfate/hydroxide
Mannitol/sorbitol
Polyethylene glycol electrolyte lavage
solution

Agents to alkalinize urine or blood

Sodium bicarbonate

Other therapeutic agents useful in the

treatment of Poisoning
Agent
Corticosteroids
Diazepam
Adrenaline
Furosemide

Indications
Acute allergic reactions,
bronchoconstriction, laryngeal
edema
Convulsions, excitation,
anxiety, hypertonia
Anaphylactic shock, cardiac
arrest
Fluid retention, LVF

Other therapeutic agents useful in

the treatment of Poisoning (contd.)
Agent
Glucose
Oxygen
Magnesium
Sulfate
Mannitol
Dopamine

Indications
Hypoglycemia
Hypoxia
Cardiac arrhythmias
Cerebral oedema, Fluid
retention
Hypotension

Some common Antidotes

Activated Charcoal
It is a fine black odorless powder
Produced in a two-step process
First step is pyrolysis of carbonaceous
materials such as wood, coconut etc.
Followed by treatment at high temperatures
with a variety of activating (oxidizing agents)
such as steam or carbon dioxide to increase its
adsorptive capacity by forming an internal
maze of pores with a huge surface area

Activated Charcoal
It decreases the systemic absorption of a number of
drugs like aspirin, acetaminophen, barbiturates,
phenytoin, cyclic antidepressants and organic
materials
It is administered as a slurry in water, more
palatable preparations are available

Activated Charcoal
Single Dose: 1gm/kg orally or by gastric tube
Repeat dose: 15-20 gm every 4-6 hours if the
amount of the drug ingested is greater than
one-tenth of the usual charcoal dose e.g. an
aspirin ingestion of more than 6-10 gm.
Contraindications:
GI ileus or obstruction
Acid or alkali ingestion

Activated Charcoal
Adverse effects:
- Constipation ( can be prevented by coadministration of a cathartic)
- Distension of stomach with potential risk of
aspiration
- Intestinal bezoars with obstruction

Atropine
Mechanism of action: It is a parasympatholytic agent
which blocks the action of acetylcholine at
muscarinic receptors
Indications:
1. Correction of bronchorrhea and excessive
salivation in OP and Carbamate poisoning
2. To improve heart rate in drug induced atrioventricular conduction impairment e.g. digitalis,
beta blockers, OP and carbamate poisoning

Atropine
Adverse Effects:
- Dryness of mouth, blurred vision, cycloplegia,
mydriasis, urinary retention, tachycardia,
aggravation of angina, constipation
Dose:
OP and Carbamate poisoning: 1-5 mg stat. Repeat
every 5-10 minutes till atropinization is
achieved
- Heart rate more than 100/minute, clear lungs,
normal bowel sounds and pupils at mid point

Atropine
Dose for Drug induced bradycardia:
For adults 0.5-1mg I/V. Repeat as needed. 3 mg is
full vagolytic dose for adults
Formulations:
Atropine sulfate injection 0.6mg/ml
Infusion of 100 ml bottles containing 1mg/ml

Acetyl Cysteine
(N-acetyl cysteine, NAC)
Mechanism of action: It is a sulfhydryl group
donor substituting for the livers usual
sulfhydryl donor Glutathione
Indications:
Acetaminophen (paracetamol) overdose
Other hepatotoxic agents like Carbon
tetrachloride, Ethylene dibromide

Acetyl Cysteine
(N-acetyl cysteine, NAC)
Dosage : Oral
Loading dose :140 mg/kg of the 10% or 20%
solution diluted to 5% in juice or soda
Maintenance dose: 70 mg/kg every 4 hours for 17
doses or 6 doses if no evidence of hepatotoxicity
Intravenous administration: Dosage regime is
given alongwith the drug.
In UK, it is 150 mg/kg in 500 ml of D5W over 4
hours, then 100 mg/kg in 1000 ml of D5W over
16 hours

Flumazenil
Mechanism of action: Highly selective antagonist of
benzodiazepine receptors
Indications:
1. Rapid reversal of benzodiazepine overdose
induced coma and respiratory depression, both
as a diagnostic tool and potential substitute of
endo-tracheal intubation.
2. Post operative reversal of benzodiazepine
sedation for surgical procedures and as an
adjunct in weaning patients from ventilators

Flumazenil
Adverse Effects:
1. Acute withdrawal in benzodiazepine addicts
(hyperexcitability, tacchycardia)
2. May precipitate seizures or arrhythmias in patients
with cyclic antidepressants overdose
Dosage:
1. Benzodiazepine overdose: Administer 0.2 mg I/V,
repeat every 30 seconds to a maximum of 3 mg.
2. Reversal of anaesthetic dose of benzodiazepine:
0.2 mg given intravenously is usually enough

Naloxone
Mechanism of action: It is a pure opioid antagonist
with no agonist activity
Indications:
1. Reversal of acute opioid intoxication manifested
by coma, respiratory depression or hypotension
2. Empiric therapy for stupor or coma suspected to
be caused by opioid overdose
Dose: 0.4-2 mg I/V, may repeat at 2-3 minute
intervals. Maximum dose is 10-15 mg

Naloxone
Adverse effects: Relatively Safe drug
1. In opioid addict may precipitate withdrawal
syndrome.
2. Do not give if the patient is agitated. Give only
if there is altered sensorium with resp. rate less
than 12 and pupillary constriction

Methylene blue
Blue dye used in acute methemoglobinemia
Converts methemoglobin to hemoglobin
Available in 10ml ampules containing
10mg/ml
Dose : 1-2mg/kg slowly I/V over 5 minutes
Maximum dose : 7 mg/kg

Chelating Agents
Certain organic compounds are capable of forming
coordinate bonds with metals through two or more
atoms of the organic compound; such organic
compounds are called chelating agents. The
compound formed by a chelating agent and a
metal is called a chelate. A chelating agent that has
two coordinating atoms is called bidentate; one
that has three, tridentate;

Chelating Agents
Calcium disodium EDTA: Given by parenteral
route ,used in lead poisoning
May cause nephrotoxicity and Zinc depletion
Penicillamine: available by oral route, effective
in chelating lead, mercury and copper, may cause
allergic reactions, weekly measurement of metals
is needed to know the need for continued
therapy, treatment may be given for 3 months

Chelating Agents
BAL (Dimercaprol, British antilewisite)
Used for arsenic, mercury and lead and gold
poisoning, has to be given by deep I/M injection
causes many adverse effects
DMSA (Succimer,2,3-dimercaptosuccinic acid)
It is a water soluble analog of Dimercaprol. Used
in lead and mercury poisoning. Also used in
arsenic poisoning. Available both as oral and
parenteral preparations. Less toxic as compared
to BAL