Overview of Antidotes

An antidote is a substance that counteracts poisoning or toxicity. Substances that can cause poisoning include heavy metals (from occupation, treatments, or diet), alcohols, environmental toxins, and medications. An increase in the concentration of these substances to toxic levels can occur accidentally or intentionally, resulting in both acute and chronic presentations. Some substances can be detected using specific laboratory tests, whereas the detection of others relies on nonspecific findings. Thus, it is important to recognize substance poisoning by history, individual risk factors, and physical examination. Antidotes along with supportive care and monitoring are part of the management.

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Heavy Metal Poisoning

Copper

  • Accumulation seen in Wilson disease; results from high intake (increased absorption or reduced excretion)
  • Toxicity presentation:
    • Abdominal pain, vomiting, gastric bleeding (hematemesis), diarrhea
    • Hypotension 
    • Jaundice
    • Liver toxicity 
    • Psychiatric symptoms (behavioral changes)
    • Altered mentation
  • Antidotes:
    • D-penicillamine (primary chelator)
    • Trientine (2nd line)
  • Other treatment: zinc (reduces the absorption of copper)

Iron

  • Accumulation due to accidental ingestion or chronic multiple transfusions
  • Toxicity presentation:
    • Lethargy/coma
    • Hypotension
    • GI symptoms (nausea, vomiting, abdominal pain)
    • Hematemesis
    • Bowel obstruction
    • Liver dysfunction
    • Renal dysfunction
    • Anion gap metabolic acidosis 
    • ↓ HCO3 levels 
  • Antidotes:
    • Deferoxamine 
    • Deferasirox 
    • Deferiprone

Lead

  • Toxicity seen due to ingestion or inhalation of lead (from lead paint, lead bullets, contaminated water)
  • Toxicity presentation:
    • Lead lines on gingiva (Burton lines) 
    • Systemic symptoms (fatigue, irritability, insomnia, joint/muscle aches)
    • GI symptoms (abdominal pain, constipation, anorexia)
    • CNS symptoms (headache, short memory loss, peripheral neuropathy, wrist drop, foot drop)
    • Encephalopathy and mental deterioration in children
    • Dense metaphyseal lines of long bones on X-ray
  • Antidotes:
    • Succimer (2,3-dimercaptosuccinic acid (DMSA))
    • Calcium disodium ethylenediaminetetraacetic acid (EDTA)
    • Dimercaprol

Mercury

  • Toxicity arising from occupational exposure (mining, manufacturing of thermometers), dentistry (tooth fillings), ingestion of contaminated fish
  • Toxicity presentation:
    • Conjunctivitis
    • Stomatitis, increased salivation
    • Cough, dyspnea
    • Nausea, vomiting
    • Dermatitis
    • Peripheral neuropathy, paresthesia
    • Chronic changes: neuropsychiatric (depression or mood changes or memory loss, neuropathy, paresthesia), rash, hair loss
  • Antidotes:
    • DMSA
    • Unithiol (2,3-dimercaptopropane-1-sulfonate (DMPS))
    • Dimercaprol
    • Penicillamine

Medication Overdose

Acetaminophen

  • Toxicity presentation:
    • Asymptomatic initially (1st 24 hours)
    • Nausea, vomiting, anorexia
    • ↑ Liver enzymes
    • Hepatotoxicity
  • Antidotes:
    • N-acetylcysteine 
    • Charcoal if administered < 4 hours of ingestion

Anticholinergic toxicity (e.g., atropine, diphenhydramine)

  • Toxicity presentation:
    • Dry mouth, dry skin
    • Blurry vision, mydriasis
    • Hyperthermia
    • Urinary retention
    • ↓ Bowel sounds 
  • Antidotes: 
    • Physostigmine
    • Control hyperthermia, IV fluids

Benzodiazepines

  • Toxicity presentation:
    • Slurred speech
    • Unsteady gait
    • Drowsiness
    • Respiratory depression
  • Antidote: Flumazenil (competitive antagonist of benzodiazepine)

Beta-blockers

  • Toxicity presentation:
    • Bradycardia
    • Hypotension
    • ↓ Consciousness or delirium
    • Seizures
    • Bronchospasm
    • Hypoglycemia
  • Antidotes:
    • Atropine
    • Glucagon

Digitalis (digoxin)

  • Toxicity presentation:
    • GI symptoms (abdominal pain, nausea, vomiting, diarrhea)
    • Anorexia, fatigue
    • Visual changes (diplopia, blindness, photophobia)
    • CNS symptoms (confusion, weakness)
    • Bradycardia, cardiac arrhythmias
    • Hyperkalemia (due to inhibition of the Na+-K+-ATPase)
  • Antidote: Anti-digoxin Fab fragments

Heparin

  • Toxicity presentation: 
    • Bruising
    • Excessive hemorrhage 
  • Antidote: Protamine sulfate

Opioids

  • Toxicity presentation: 
    • CNS symptoms (euphoria, drowsiness, slurred speech, seizures, pinpoint pupils)
    • GI symptoms (nausea, vomiting, constipation)
    • Respiratory depression
  • Antidote: Naloxone

Salicylates

  • Toxicity presentation: 
    • Tinnitus
    • Fever
    • Nausea and vomiting
    • Early hyperpnea (respiratory alkalosis) 
    • Later develops into anion gap metabolic acidosis
  • Antidotes: 
    • NaHCO3 (urine alkalinization)
    • Decontamination with activated charcoal if ingestion is within 2 hours
    • Supplemental glucose even if serum glucose is normal (as salicylates decrease cerebral glucose levels)
    • Hemodialysis

Tricyclic antidepressants (TCAs)

  • Toxicity presentation:
    • CNS symptoms (mental status changes, seizures)
    • Respiratory depression
    • Cardiovascular symptoms (tachycardia, hypotension, prolonged QT, arrhythmias)
    • Anticholinergic symptoms (dry mouth, blurred vision, dilated pupils, urinary retention, flushing, hyperthermia)
  • Antidotes: 
    • O2
    • IV fluids
    • IV NaHCO3 for arrhythmias
    • Benzodiazepines for seizures
    • Decontamination with activated charcoal if ingestion was within 2 hours

Warfarin

  • Toxicity presentation:
    • Bruising
    • Excessive hemorrhage
    • Skin necrosis
  • Antidotes: 
    • Vitamin K (delayed reversal)
    • Fresh frozen plasma (immediate reversal)
    • Prothrombin complex concentrate

Toxic Alcohol Poisoning

Methanol and ethylene glycol are found in automotive coolants (antifreeze) and deicing solutions, fuel, cleaners, windshield wiper fluids, solvents, and other industrial products.

Methanol

  • Toxicity presentation:
    • Blurred vision with central scotoma
    • Afferent pupillary defect (ominous sign)
    • Headaches
    • Mental status changes
    • Nausea and vomiting
    • Hypotension
    • ↑ Anion gap metabolic acidosis
    • Coma
  • Antidotes: 
    • Fomepizole (preferred)
    • Ethanol
    • Hemodialysis in severe cases (acidosis, end-organ damage)

Ethylene glycol

  • Toxicity presentation:
    • Tetany
    • Flank pain
    • Hematuria
    • Oliguria
    • ↑ Anion gap metabolic acidosis
    • Calcium oxalate crystals in urine
    • Kidney failure
    • Cranial nerve palsy
  • Antidotes: 
    • Fomepizole (preferred)
    • Ethanol
    • Hemodialysis in severe cases (acidosis, end-organ damage)

Arsenic and Cyanide Poisoning

Arsenic

  • Exposure can be from natural sources (volcanic eruption), occupational sources (smelting), or contaminated medications, water, or animal feeds.
  • Toxicity presentation:
    • Garlic breath
    • Dehydration
    • GI symptoms (vomiting, watery diarrhea)
    • Cardiovascular symptoms (hypotension, QT prolongation, cardiac arrhythmias)
    • Skin manifestations: pigmentation (↓ or ↑), hyperkeratosis
    • Stocking-glove neuropathy (burning, painful hypersensitivity, distal weakness, and hyporeflexia)
    • Liver cancer (angiosarcoma)
    • Lung cancer 
  • Antidotes: 
    • Dimercaprol 
    • DMSA

Cyanide

  • Exposure can be from domestic fires (cyanide released from the combustion of products), occupation (mining, manufacturing), sodium nitroprusside, or diet (pits/seeds of some fruits).
  • Toxicity presentation:
    • Bitter almond breath
    • Pink or cherry red skin 
    • Nausea and vomiting
    • Metabolic acidosis 
    • Initial hypertension, then hypotension 
    • Hyperventilation 
    • Headache, vertigo, seizures 
    • Renal and hepatic failure
  • Antidotes: 
    • Hydroxocobalamin
    • Sodium thiosulfate
    • Induce methemoglobinemia using nitrites (e.g., amyl nitrite, sodium nitrite) if the above medications are unavailable.

Miscellaneous Antidotes

Anticholinesterase poisoning (organophosphate, insecticides)

  • Toxicity presentation (cholinergic):
    • Pinpoint pupils
    • Sweating, salivation
    • Bronchoconstriction
    • Vomiting and diarrhea
    • CNS stimulation followed by CNS depression
    • Muscle fasciculations, weakness, paralysis
    • Death from respiratory failure
  • Antidotes: 
    • Atropine 
    • Pralidoxime

Carbon monoxide

  • From fire-related smoke inhalation; also common in winter months (from fuel-burning devices, vehicles in poorly ventilated areas)
  • Toxicity presentation:
    • Confusion 
    • Rose cheeks and bright cherry lips 
    • Headache, dizziness
    • Decreased visual acuity 
    • Nausea
    • Malaise 
    • Tachycardia, myocardial ischemia, arrhythmias 
  • Antidotes: 
    • 100% O2
    • Hyperbaric O2

Methemoglobin

  • Methemoglobinemia has genetic and acquired (medications such as dapsone, antimalarials) causes.
  • Toxicity presentation:
    • Cyanosis
    • Chocolate-colored blood
    • Arrhythmias
    • Chest pain, palpitations
    • Acidosis
    • Confusion
    • Seizures, coma
  • Antidotes: 
    • Methylene blue
    • High dose of vitamin C

Clinical Relevance

  • Methanol poisoning: Methanol is a type of non-consumable alcohol (wood alcohol) mostly used in the manufacture of fuel, solvents, and antifreeze. Methanol ingestion results in symptoms such as visual blurring, central scotoma, afferent pupillary defect, headaches, mental status changes, nausea, vomiting, and anion gap metabolic acidosis. The most dangerous complications of methanol poisoning are vision loss and coma. Management is with fomepizole (blocks alcohol dehydrogenase) and ethanol, and hemodialysis.
  • Ethylene glycol poisoning: Ethylene glycol is an alcohol used as a raw material in the manufacture of polyester fibers and antifreeze formulations. Toxicity presentation includes flank pain, hematuria, oliguria, anion gap metabolic acidosis, calcium oxalate crystals in the urine, and kidney damage. Management involves the administration of fomepizole (blocks alcohol dehydrogenase) and ethanol, and dialysis.
  • Anticholinergic toxicity: a condition occurring from the overdose of atropine or diphenhydramine. Anticholinergic toxicity is characterized by dry mouth, dry skin, blurry vision, mydriasis, hyperthermia, urinary retention, and decreased bowel sounds. Management involves the administration of physostigmine and the control of hyperthermia.
  • Organophosphate toxicity: Organophosphates irreversibly inhibit the enzyme acetylcholinesterase. Features of toxicity include pinpoint pupils, sweating, salivation, bronchoconstriction, vomiting, diarrhea, CNS stimulation followed by CNS depression, muscle fasciculations, weakness, paralysis, and death from respiratory failure. Management involves the administration of both atropine and pralidoxime.
  • Acetaminophen toxicity: occurs when large doses of acetaminophen (> 7.5 g in adults, and > 150 mg/kg in pediatrics) are administered. Many patients remain asymptomatic initially (1st 24 hours). Features of acetaminophen toxicity include nausea, vomiting, anorexia, elevated liver enzymes, and hepatotoxicity. Management involves measuring acetaminophen blood levels, administering activated charcoal if the patient presents within 4 hours of intoxication, and administering N-acetylcysteine (to restore glutathione levels).
  • Methemoglobinemia: a condition characterized by elevated levels of methemoglobin in the blood. Methemoglobin is the oxidized form of hemoglobin, where the heme iron has been converted from the usual ferrous (Fe2+) to ferric (Fe3+) form. The Fe3+ form cannot bind oxygen, leading to tissue hypoxia. The condition is fatal in case of significant elevation of methemoglobin (> 70%). Diagnosis is established by measuring methemoglobin levels in blood using co-oximetry. Treatment is using methylene blue or ascorbic acid.
  • Benzodiazepine toxicity: a condition resulting from benzodiazepine overdose (e.g., for anxiety, sleep). Symptoms of benzodiazepine toxicity include slurred speech, unsteady gait, drowsiness, and respiratory depression, especially if co-administered with alcohol or opioids. Patients usually have normal vital signs and pupillary size. Flumazenil is used as an antidote.
  • CO poisoning: CO is an odorless, tasteless, colorless, nonirritating gas formed by hydrocarbon combustion (fires, car exhaust, gas heaters). Carbon monoxide poisoning results in impaired O2 transport and utilization. Features of CO poisoning include confusion, headache, dizziness, decreased visual acuity, rose cheeks, coma, and death. Management includes the use of 100% O2; hyperbaric O2 is used if O2 therapy fails.

References

  1. Barrueto, F. (2021). Beta blocker poisoning. UpToDate. Retrieved June 20, 2021, from https://www.uptodate.com/contents/beta-blocker-poisoning
  2. Beauchamp, G., Kusin, S., Elinder, C. (2021). Mercury toxicity. UpToDate. Retrieved June 20, 2021, from https://www.uptodate.com/contents/mercury-toxicity
  3. Boyer, E., Weibrecht, K. (2021). Salicylate (aspirin) poisoning in adults. UpToDate. Retrieved June 20, 2021, from https://www.uptodate.com/contents/salicylate-aspirin-poisoning-in-adults
  4. Clardy, P., Perry, H. (2021). Carbon monoxide poisoning. UpToDate. Retrieved June 20, 2021, from https://www.uptodate.com/contents/carbon-monoxide-poisoning
  5. Dart, R., Heard, K. (2020). Acetaminophen (paracetamol) poisoning in adults: Treatment. UpToDate. Retrieved April 1, 2021, from https://www.uptodate.com/contents/acetaminophen-paracetamol-poisoning-in-adults-treatment
  6. Desai, S., Su, M. (2021). Cyanide Poisoning. UpToDate. Retrieved June 20, 2021, from https://www.uptodate.com/contents/cyanide-poisoning
  7. Goldman, R. (2021). Arsenic exposure and poisoning. UpToDate. Retrieved June 20, 2021, from https://www.uptodate.com/contents/arsenic-exposure-and-poisoning
  8. Hu, H., Goldman, R. (2019). Lead exposure and poisoning in adults. UpToDate. Retrieved April 2, 2021, from https://www.uptodate.com/contents/lead-exposure-and-poisoning-in-adults
  9. Levine, M. (2020). General approach to drug poisoning in adults. UpToDate. Retrieved April 1, 2021, from https://www.uptodate.com/contents/general-approach-to-drug-poisoning-in-adults
  10. Liebelt, E. (2021). Acute iron poisoning. UpToDate. Retrieved June 20, 2021, from https://www.uptodate.com/contents/acute-iron-poisoning
  11. Royer, A., Sharman, T. (2021). Copper toxicity. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. https://www.ncbi.nlm.nih.gov/books/NBK557456/
  12. Salhanick, S. (2021). Tricyclic antidepressant poisoning. UpToDate. Retrieved June 20, 2021, from https://www.uptodate.com/contents/tricyclic-antidepressant-poisoning
  13. Sivilotti, M. (2020). Methanol and ethylene glycol poisoning: Management. UpToDate. Retrieved April 1, 2021, from https://www.uptodate.com/contents/methanol-and-ethylene-glycol-poisoning-management

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