Atropine (Treatment)

Atropine is an anticholinergic agent which acts as a competitive antagonist at autonomic postganglionic muscarinic receptors. It is used to treat organophosphate and carbamate toxicity, symptomatic bradycardia (e.g. in β-blocker toxicity), and chemical weapons nerve agent toxicity.

• Also see: Cholinergic Toxicity, organophosphate toxicity.
• A rapid loading protocol and infusion is used.
• Adult:
  • 💊 Atropine 1.2 mg IV, double the dose q5min until target end points for atropinization reached, then start infusion; very high doses (up to 100 mg) may be required.
  • 💊 Atropine 10-20% of total loading dose per hour IV infusion, usually 0.5-5 mg/hr.
• Child:
  • 💊👶 Atropine 0.05 mg/kg (up to 1.2 mg) IV, double the dose q5min until target end points for atropinization reached, then start infusion; very high doses may be required.
  • 💊👶 Atropine 10-20% of total loading dose per hour IV infusion.
• Titrate to atropinization target end points:
  • Clear chest, no auscultatory wheeze
  • Resolution of symptomatic bradycardia (e.g. in adults HR > 80bpm, systolic BP >80 mmHg)
• Observe for signs of over-atropinization:
  • Confusion
  • Pyrexia
  • Absent bowel sounds

• Also see: cholinergic toxidrome.
• Adult: 💊 Atropine 0.6 mg IV, double the dose q5min until target end points for atropinization reached; max cumulative dose 3 mg.
• Child: 💊👶 Atropine 0.02 mg/kg (up to 0.6 mg) IV, double the dose q5min until target end points for atropinization reached; max cumulative dose 3 mg.
• Titrate to atropinization target end points:
  • Clear chest, no auscultatory wheeze
  • Resolution of symptomatic bradycardia (e.g. in adults HR > 80bpm, systolic BP >80 mmHg)
• Observe for signs of over-atropinization:
  • Confusion
  • Pyrexia
  • Absent bowel sounds

• Also see: Beta Blocker Toxicity.
• Adult: 💊 Atropine 0.6 mg IV, q15min; max cumulative dose 3 mg.
• Child: 💊👶 Atropine 0.02 mg/kg (up to 0.6 mg) IV; max cumulative dose 3 mg.

Pregnancy rating: A (AU/NZ)

Lactation: Small amounts excreted in breast milk.

• CV: Paradoxical bradycardia (with low doses or given slowly), tachyarrhythmia
• CNS: Delirium, coma, blurred vision
• Skin: Flushing
• GI: Nausea, vomiting, constipation, xerostomia
• GU: Urinary retention

Mechanism of action: Atropine is a competitive antagonist at autonomic postganglionic muscarinic receptors. Its clinical effects manifest primarily with ↑ heart rate, ↓ secretions, bronchodilation, and mydriasis.

Absorption:

• Oral bioavailability: variably reported between 50-95%
• GI tract absorption: From small intestine
• IM bioavailability: 50%
• Tmax:
  • IV: Almost immediate
  • Oral: 60 mins
  • IM: 11-30 mins
  • SC: 34 ± 23 mins
  • Inhaled: 15-114 mins

Distribution:

• Vd: 2-4 L/kg (large Vd; widely distributed in the body)
• Distribution t½ after IV: 1 min; rapid decline in serum concentration within first 10 mins
• Lipid solubility:
  • Crosses blood brain barrier
  • Crosses placenta
  • Excreted in breast milk in small amounts
• Protein binding: 14-22%

Metabolism: Hepatic metabolism - hepatic enzyme hydrolysis.

• Stereoselective metabolism: biologically active L-enantiomer metabolized, biologically inactive D-enantiomer excreted unchanged in urine.
• Metabolites: Tropine, noratropine, atropine-N-oxide, tropic acid.

Excretion:

• Elimination occurs in two phases: rapid phase t½ = 4 hrs; slow phase t½ = 13 hrs
• Hepatic clearance: 519 ± 147 mL/min
• Renal clearance: 90% excreted in urine over 24 hours. 30-50% as unchanged drug.

Formulation:

• Tablets: 0.4 mg.
• Ampoules of 0.5-0.6 mg/mL or 3 mg/10mL.
• Eye drops: atropine sulfate 1%.
• IM autoinjector: 2mg/0.7mL.

Further Reading: