Antidotes

by Hamidreza Reihani and Elham Pishbin

An antidote is an agent or drug that can reverse the toxic effects of poisoning. The base of clinical practice in the treatment of toxicities is cardiopulmonary stabilization, decontamination, enhancing elimination and supportive management. Antidotes are indicated in some specific and well-defined situations, and they are not routinely administered in toxin exposures. Therefore, the physician should know the indications and contraindications of each antidote. Administration of the pharmacologic antagonists may worsen the outcome in some situations and are not recommended.

There is usually enough time to start the treatment after supportive care and evaluation of the patient. However, there are a few indications that antidotes should be administered as soon as possible to prevent major complications and death. Cyanide antidotes for cyanide toxicity, naloxone for severe opium overdose and atropine for organophosphate poisoning and gas agents are some examples.

The antidotes administered in clinical practice are not a great deal. There is a list of essential antidotes and a brief explanation of their character and application.

Antidotes and their characteristics (A - E)

AntidoteIndications/precautionsDosage/administration
AtropineGeneral information
• Anticholinergic agent
• Competitive muscarinic antagonist
Indications
• Organophosphate poisoning
• Carbamates
• Nerve agents
Precautions
• Excessive doses lead to anticholinergic symptoms
Dose
• Start with 1-2 mg IV (adults), 0.02 mg/kg IV (children)
• Double the dose every 2-3 minute to achieve atropinization
Administration
• Infusion of 10-20% of stabilizing dose/hour
• Large doses may be required
• There are auto-injectors for rapid use
Other
• Drying of respiratory secretions is the goal
• Tachycardia is not the endpoint
CalciumGeneral information
• Calcium chloride 10% (1 g /10 mL), (27.2 mg/mL elemental Ca)
• Calcium gluconate 10% (9 mg/mL elemental Ca), one-third of the calcium in strength of calcium chloride
Indications
• Calcium channel blockers toxicity
• Hydrofluoric acid exposure
• Hyperkalemia
• Hypermagnesaemia
Precautions
• Calcium chloride extravasation can lead to soft tissue necrosis, preferably administered via central line
• Continuous monitoring is recommended
Dose
• 1 gram calcium chloride (10 mL), (0.15mL/kg in children)
• 10-30 mL of calcium gluconate
Administration
• IV bolus over 5 minutes
• Repeated doses every 10-20 minutes if needed
• Infusion can be administered
Other
• Topical calcium gel or local injection of calcium gluconate for hydrofluoric acid skin burns
• Intra-arterial or IV with a Bier block for extremity exposure
CiproheptadineGeneral information
• An antihistaminic and antiserotonergic agent
• Has anticholinergic effects as well
Indications
• Control of symptoms in serotonin syndrome
Precautions
• May cause anticholinergic effects
Dose
• 8 mg (adults), 4 mg (children) not approved
Administration
• Oral
• Can be repeated every 8 hours until 24 hours

DeferoxaminGeneral information
• Iron-chelating agent
• Converts it to a water-soluble complex excreted by urine
Indications
• Systemic iron toxicity
• Iron levels > 500 µg/dL
• Multiple pills on radiography
Precautions
• Hypotension may occur at rapid rates
• Cardiac monitoring is needed
• Avoid infusion more than 24 hours
Dose
• Start with15 mg/kg/h
Administration
• IV infusion
• Infusion rate could be increased
Other
• Evaluate patient after 6 hours
• The urine color will become red
Digoxin immune FabGeneral information
• Fab fragments of antibodies to digoxin
• Reverse the dangerous cardiac effects of digitalis
Indications
• Acute and chronic digoxin overdose
• Other cardiac glycosides poisoning
Precautions
• Close monitoring; ready for resuscitation
• Monitor serum free level of digoxin
Dose
• Acute overdose: 5 vials; for unstable patients 10-20 vials; can be calculated if the ingested dose is known
• Chronic overdose: can be calculated by serum digoxin level; start with 2 vials
Administration
• Bolus in life threatening conditions, otherwise infusion
Other
• For other cardiac glycoside poisoning start with 5 vials
Dimercaprol
(BAL)
General information
• Heavy metal chelator
Indications
• Severe lead, inorganic arsenic and mercury poisoning
Precautions
• Many severe adverse effects
• Nephrotoxic
• Administered in ICU
Dose
• 3 mg/kg
Administration
• IM every 4 hours for 48 hours
Other
EthanolGeneral information
• Blocks the formation of toxic metabolites of alcohols
Indications
• Methanol and ethylene glycol poisoning
Precautions
• Serum ethanol levels monitored every 1-2 hours
• The dose should be doubled during dialysis
Dose/ Administration
• IV: loading (10 mL/kg of 10% IV solution), maintenance (1-2 mL/kg/h of 10% IV solution)
• Oral: loading (1.5-2 mL/kg 80-proof liquor), maintenance (0.2-0.5 mL/kg/h)
Other
• Maintain blood ethanol concentration between 100-150 mg/dl
provided by author

Antidotes and their characteristics (F - I)

AntidoteIndications/precautionsDosage/administration
FlumazenilGeneral information
• Competitive benzodiazepine antagonist
• Not used routinely in benzodiazepine poisoning
Indications
• Reversal of procedural sedation
• Pediatric poisoning (limited use)
Precautions
• May cause withdrawal
• May induce seizure
Dose
• 0.2 mg, 0.01 mg/kg (children)
• Repeat up to the desired effect or 3 mg
Administration
• IV over 30 seconds
Other
• Not used in mixed drug overdose
FomepizoleGeneral information
• An alcohol dehydrogenase inhibitor
Indications
• Methanol and ethylene glycol toxicity
Precautions
Dose
• Loading dose = 15 mg/kg
• Maintenance dose = 10 mg/kg q12 hours
Administration
• Infusion in 100 ml normal saline or 5% dextrose in 30 minutes
Other
• In dialyzed patients is given every 4 hours or continuous infusion
GlucagonGeneral information
• Increase cAMP**
• Positive inotropic and chronotropic similar to beta-agonists
Indications
• β-blocker toxicity
• Calcium channel blocker toxicity
Precautions
• Induces vomiting, consider airway management
Dose
• 5-10 mg (adults), 0.05-0.1 mg/kg (children)
Administration
• The first dose is IV bolus, if there is a clinical response, start infusion
Other
HydroxocobalaminGeneral information
• A precursor of Vitamin B12
• Hydroxyl group is displaced by cyanide and form cyanocobalamin
Indications
• Cyanide toxicity
Precautions
• It's a safe drug
Dose
• 5 g, repeat if needed; 70 mg/kg (children)
Administration
• Infusion in 100 normal saline in 15 minutes
Other
• Skin and urine orange-red discoloration
Insulin (High dose)General information
• It has strong inotropic effects
Indications
• Calcium channel blocker toxicity
• Βeta-blocker toxicity
Precautions
• Glucose level should be monitored every 10 minutes
• Hypokalemia be considered
Dose/ Administration
• 1 IU/kg IV bolus of short acting insulin, followed by 0.5-1 IU/kg/hr
• Glucose 25 g (dextrose 50%) before starting insulin, then 25 g/hr according to glucose level
Other
• Higher doses were administered in studies
Intravenous Lipid EmulsionGeneral information
• 20% lipid emulsion as a parenteral nutrient
Indications
• Overdose by drugs with high protein binding and large volume of distribution, e.g. Local anesthetics, β-blockers and calcium channel blockers
Precautions
Dose/Administration
• 1.5 ml/kg IV bolus
• 0.25 ml/kg/minute
Other
• Until hemodynamic stability restored
provided by author

Antidotes and their characteristics (M - I)

AntidoteIndications/precautionsDosage/administration
Methylen blueGeneral information
• It reduces methemoglobin (MetHb) to hemoglobin
Indications
• Methemoglobin-forming agents toxicity
• Symptomatic methemoglobinemia
• MetHb levels >20% in asymptomatic patients
Precautions
• Pulse oximetry is unreliable in methemoglobinemia
• Hemolysis in G6PD deficiency
Dose
• 1-2 mg/kg IV, 1 mg/kg (children)
Administration
• Slow IV injection, may repeat 30-60 minutes later
Other
• MetHb levels measured frequently
N-acetylcysteineGeneral information
• Preventing hepatocellular injury in severe acetaminophen toxicity
Indications
• Serum acetaminophen concentration above toxic level
• Hepatocellular injury
Precautions
• Oral therapy may not be tolerated due to its taste and odor
Dose/Administration
• Oral: loading (140 mg/kg), then (70 mg/kg q 4 hours) for 17 doses
• IV: loading 150 mg/kg in 30-60 minutes then 50 mg/kg over 4 hours, 100 mg/kg infused over next 16 hours
Other
NaloxoneGeneral information
• An opioid antagonist
Indications
• For reversing the opioid effects, respiratory and CNS depression
Precautions
• Re-sedation may occur due to short half-life of naloxone
• Withdrawal in chronic users
Dose
• Start: 0.1 to 0.4 mg; 0.01 mg/kg (children)
• Repeat every 2-3 minutes up to 10 mg
Administration
• Intravenously, intramuscularly, or subcutaneously
Other
• Start with larger doses if respiratory depression exist
• Infusions may be required
OctreotideGeneral information
• Synthetic analogue of somatostatin
Indications
• Hypoglycemia due to sulfonylurea
Precautions
• Break through hypoglycemia may occur
Dose/Administration

• 50 µg IV then 25 µg/h or
• 100 µg IM or SC every 6 hours

PhysostigmineGeneral information
• Reverse anticholinergic syndrome
Indications
• For CNS symptoms (delirium, seizure) due to anticholinergic drugs
Precautions
• Contraindicated in bradycardia, AV block and bronchospasm
Dose
• 0.5 – 1 mg (adults), 0.02 mg/kg (children)
Administration
• IV slowly in 2 minutes or IM
• Repeat in 10 to 30 minutes if needed
Other
• In rapid administration cholinergic symptoms may occur
PralidoximeGeneral information
• Reactivate cholinesterase inhibition due to organophosphates
Indications
• Organophosphates poisoning
• Nerve agents
Dose
• Loading: 1-2 g IV; 25-50 mg/kg (children)
• Maintenance: 500 mg/hr or 1-2 g q4-6h; 10-20 mg/kg/hour (children)
Administration
• IV infusion in 0.9% saline
Other
• Should be administered in the early phase before irreversible binding occurs
PyridoxineGeneral information
• Vitamin B6 is essential for GABA production
Indications
• Isoniazid, hydrazine and Gyromitra poisoning
• Ethylene glycol poisoning
Dose/Administration

• 1 gram for each gram of isoniazid, 70 mg/kg (children), maximum 5 gram
• 50 mg IV every 6 hours for ethylene glycol toxicity
• 0.5 g/min infusion until the seizure stops
Sodium bicarbonateGeneral information
• Hyperosmolar Sodium Bicarbonate Injection
Indications
• Cardiotoxicity due to fast sodium channel blockade (e.g., TCA* poisoning)
• Urine alkalinization
Precautions
• Hypokalemia is a concern
• Serum pH maintained between 7.50-7.55
Dose
• Start with 1-2 mEq/kg, further doses may be needed
Administration
• First dose administered bolus
• Other bolus doses or infusion if required
Other
• Given only if there is evidence of cardiotoxicity, such as QRS widening and ventricular dysrhythmias
Sodium calcium edetate
(EDTA)
General information
• IV heavy metal chelator
Indications
• Severe lead toxicity
• Lead level > 70 µg/dl
Precautions
• Patient should be admitted in hospital
• Nephrotoxicity, ECG changes and liver test disturbance may occur
Dose
• 25-75 mg/kg/day
Administration
• Continuous infusion for 5 days
Other
• Usually starts 4 hours after first dimercaprol (BAL) injection
Sodium thiosulfateGeneral information
• Help the body to detoxify cyanide
Indications
• Cyanide poisoning
Precautions
• In severe cases with other antidotes
Dose
• 50 ml of 25% (12.5 g; 1 ampoule) in adults; 1.65 ml/kg (children)
Administration
• IV over 10 minutes
• Repeat after 30 minutes if clinically needed
Succimer
(DMSA)
General information
• Oral metal chelator
Indications
• Symptomatic lead poisoning
• Asymptomatic lead poisoning, lead level > 60 µg/dl (adults), > 45 µg/dl (children)
Precautions
• May cause neutropenia, gastrointestinal upset and liver abnormalities
Dose
• 10 mg/kg three times a day for 1 week, then two times a day for 2 weeks
Administration
• Orally
Other
• The serum level should be monitored
provided by author

References and Further Reading

  • contributors W. Antidote: Wikipedia, The Free Encyclopedia. ; 2016 [cited 2016 20 july]. Available from: https://en.wikipedia.org/w/index.php?title=Antidote&oldid=708590648.
  • Holstege CP, Dobmeier SG, Bechtel LK. Critical care toxicology. Emergency medicine clinics of North America. 2008;26(3):715-39.
  • Erickson TB, Thompson TM, Lu JJ. The approach to the patient with an unknown overdose. Emergency medicine clinics of North America. 2007;25(2):249-81.
  • Greene S. General Management of Poisoned Patients. Tintinalli’s emergency medicine. 1. 8 ed: MC Graw Hill; 2014. p. 1207.