Lifesaving Drug Antidotes Every Emergency Doctor Must Know

1. Naloxone – The Opioid Antidote

Use: Reversal of opioid toxicity (e.g., heroin, morphine, fentanyl, oxycodone)

Mechanism: Competitive opioid receptor antagonist

Dose:

• IV/IM/SC: 0.4–2 mg every 2–3 minutes up to 10 mg
• Intranasal: 4 mg per spray

Onset: 1–2 minutes IV

Pearls: Always monitor for re-sedation, especially in long-acting opioids like methadone. Precipitation of acute withdrawal is common in opioid-dependent patients.

2. Flumazenil – The Benzodiazepine Antagonist

Use: Benzodiazepine overdose in non-dependent patients

Mechanism: Competitive GABA-A receptor antagonist

Dose:

• Initial: 0.2 mg IV over 15 seconds
• May repeat every 1 minute, max total dose: 3 mg

Warning: Contraindicated in patients with a seizure history or co-ingestion of pro-convulsant agents (e.g., TCAs). Risk of seizures is high.

Clinical Note: Flumazenil is rarely used due to the risk of precipitating seizures in mixed overdoses.

3. N-acetylcysteine (NAC) – For Acetaminophen (Paracetamol) Toxicity

Use: Acetaminophen overdose

Mechanism: Restores hepatic glutathione; detoxifies NAPQI, the toxic metabolite

IV Dose (20-hour protocol):

• 150 mg/kg over 1 hour
• Then 50 mg/kg over 4 hours
• Then 100 mg/kg over 16 hours

Oral Dose (72-hour protocol):

• 140 mg/kg loading, then 70 mg/kg every 4 hours × 17 doses

Timing: Most effective within 8 hours post-ingestion

Clinical Tip: Check serum acetaminophen level at 4 hours and plot on the Rumack-Matthew nomogram.

4. Atropine and Pralidoxime – For Organophosphate and Nerve Agent Poisoning

Use: Organophosphate and carbamate poisoning

Mechanism:

• Atropine: Antagonizes muscarinic effects
• Pralidoxime: Regenerates acetylcholinesterase

Dosing:

• Atropine: Start with 1–3 mg IV every 5–10 minutes until secretions dry
• Pralidoxime (2-PAM): 1–2 g IV over 15–30 minutes, repeated every 6–12 hours

Note: Massive doses of atropine may be required (>100 mg/day). Always titrate to respiratory secretions, not heart rate.

5. Hydroxocobalamin – For Cyanide Poisoning

Use: Smoke inhalation, industrial cyanide exposure

Mechanism: Binds cyanide to form cyanocobalamin, which is excreted renally

Dose: 5 g IV over 15 minutes; may repeat once

Color Effect: Turns urine and skin reddish-purple—this is harmless and temporary.

Tip: Avoid sodium thiosulfate if rapid action is needed, as it works slower than hydroxocobalamin.

6. Glucagon – For Beta-Blocker and Calcium Channel Blocker Overdose

Use: Symptomatic bradycardia and hypotension

Mechanism: Activates adenylate cyclase independently of beta-receptors, increasing intracellular cAMP

Dose:

• Initial: 3–5 mg IV bolus
• Maintenance: Infusion of 2–5 mg/hour

Adjuncts: High-dose insulin euglycemia therapy (HIE), calcium, vasopressors

Insight: Vomiting is a common side effect; give with antiemetics.

7. Digoxin Immune Fab – For Digoxin Toxicity

Use: Digoxin overdose with life-threatening arrhythmias or elevated potassium

Mechanism: Binds free digoxin, allowing renal excretion

Dose:

• Acute ingestion: Based on amount ingested
• Chronic toxicity: Empirical dosing (e.g., 3–6 vials)

Monitor: ECG changes, potassium normalization

Caution: Do not rely on serum digoxin levels after giving Fab—it remains elevated due to bound inactive drug.

8. Fomepizole – For Ethylene Glycol and Methanol Poisoning

Use: Toxic alcohol ingestion (antifreeze, windshield washer fluid)

Mechanism: Inhibits alcohol dehydrogenase, preventing toxic metabolite formation

Dose:

• Loading: 15 mg/kg IV
• Maintenance: 10 mg/kg every 12 hours × 4 doses, then 15 mg/kg every 12 hours

Adjunct: Hemodialysis if severe acidosis or renal failure develops

Backup: Ethanol can be used if fomepizole is unavailable

9. Methylene Blue – For Methemoglobinemia

Use: Dapsone, nitrates, local anesthetic toxicity (benzocaine)

Mechanism: Reduces methemoglobin to hemoglobin via NADPH pathway

Dose: 1–2 mg/kg IV over 5 minutes; repeat if needed

Contraindications: G6PD deficiency – risk of hemolysis

Key Sign: "Chocolate-brown" blood unresponsive to oxygen therapy

10. Calcium Gluconate – For Hyperkalemia and Calcium Channel Blocker Overdose

Use:

• Cardioprotection in hyperkalemia
• Reverse effects of CCB overdose

Mechanism: Stabilizes cardiac membrane

Dose:

• Calcium gluconate: 10 mL of 10% solution IV over 2–5 minutes
• Repeat every 10 minutes if needed

Monitor: ECG for changes; central line preferred for calcium chloride

11. Octreotide – For Sulfonylurea-Induced Hypoglycemia

Use: Persistent hypoglycemia from sulfonylureas (e.g., glipizide, glyburide)

Mechanism: Suppresses insulin secretion

Dose: 50 mcg SC every 6–12 hours or continuous IV infusion

Key Point: Always use with dextrose to stabilize glucose levels

12. Deferoxamine – For Iron Toxicity

Use: Iron overdose

Mechanism: Chelates ferric iron to form ferrioxamine, excreted in urine

Dose: 15 mg/kg/hour IV, max 6 g/day

Sign of Action: "Vin rose" or pink-red urine

When to Use: Serum iron >500 mcg/dL or severe symptoms

13. Penicillamine – For Heavy Metal Poisoning

Use: Copper, mercury, arsenic poisoning (when BAL not available)

Mechanism: Chelation

Dose: 250 mg orally four times daily

Special Use: Wilson's disease (chronic copper overload)

14. Lipid Emulsion Therapy – For Lipophilic Drug Toxicity

Use: Local anesthetic systemic toxicity (e.g., bupivacaine), beta-blockers, calcium channel blockers

Mechanism: “Lipid sink” absorbs lipophilic toxins

Dose (Intralipid 20%):

• Bolus: 1.5 mL/kg over 1 minute
• Continuous infusion: 0.25–0.5 mL/kg/min for 30–60 minutes

Caution: Avoid in patients with fat metabolism disorders

15. Protamine – For Heparin Overdose

Use: Heparin-induced bleeding

Mechanism: Binds to heparin, neutralizing its anticoagulant effect

Dose:

• 1 mg per 100 units of heparin remaining in circulation
• Max: 50 mg IV over 10 minutes

Risk: Anaphylaxis in fish-allergic or vasectomized patients

16. Vitamin K (Phytonadione) – For Warfarin Reversal

Use: Elevated INR, bleeding complications

Mechanism: Promotes hepatic synthesis of vitamin K-dependent clotting factors

Dose:

• Oral: 2.5–10 mg for non-urgent reversal
• IV: 1–10 mg for serious bleeding (infuse slowly)

Adjunct: Fresh frozen plasma or prothrombin complex concentrate (PCC) for rapid reversal

17. Leucovorin (Folinic Acid) – For Methotrexate Toxicity

Use: Methotrexate overdose or high-dose therapy

Mechanism: Bypasses dihydrofolate reductase inhibition

Dose: 10–15 mg IV every 6 hours, adjusted based on methotrexate level

Timing: Must be started within 24–36 hours of methotrexate administration

18. Sodium Bicarbonate – For Tricyclic Antidepressant (TCA) and Salicylate Poisoning

Use:

• TCA overdose with wide QRS or arrhythmias
• Salicylate-induced acidosis

Mechanism: Alkalinizes serum and urine

Dose:

• Bolus: 1–2 mEq/kg IV
• Infusion: Add 150 mEq in 1 L D5W; run at 250 mL/hour

Monitor: pH target 7.45–7.55, avoid hypokalemia