Atropine

Mechanism

Pharmacological Group and Molecular Target

Reversible competitive antagonist of muscarinic cholinergic receptors (subtypes M1, M2, M3, M4 and M5).

Detailed Mechanism of Action

Atropine binds highly selectively and competitively to muscarinic receptors in target organs of the parasympathetic and central nervous system. Its binding directly blocks the physiological actions of the neurotransmitter acetylcholine (ACh). In the context of poisoning by organophosphate compounds or carbamates (which irreversibly or reversibly inhibit the enzyme acetylcholinesterase), a massive accumulation of ACh occurs in the synaptic cleft. Atropine blocks excess acetylcholine at muscarinic receptors, preventing overstimulation that triggers bronchial constriction, profuse bronchorrhea, extreme sinus bradycardia, sweating, lacrimation, and salivation.

Pharmacokinetics

Pharmacokinetic and Toxicokinetic Profile

• Absorption: Rapid absorption after intramuscular (IM) or intravenous (IV) administration.
• Distribution: Effectively crosses the blood-brain barrier (BBB) and the placental barrier. It has a volume of distribution of 1-1.6 L/kg.
• Metabolism: Partial hepatic by enzymatic hydrolysis to inactive metabolites (atropine-n-oxide).
• Excretion: Renal; 30-50% is eliminated without structural changes in the urine.
• Elimination half-life: 2 to 4 hours (prolonged in the elderly and young children).

Indicators and dose

Specific Clinical Indications

• Acute Muscarinic Cholinergic Syndrome: Secondary to poisoning by organophosphate pesticides, carbamate pesticides or war nerve gases (such as Sarin, VX or Soman).
• Intoxication by mushrooms of the genus Amanita muscaria or Clitocybe: They contain muscarine in high concentrations.
• Symptomatic bradycardia of vagal origin or secondary to beta-blocking drugs.

Dosage Scheme and Infusion Protocols

Rapid Atropinization Protocol in Cholinergic Syndrome

The goal of treatment is not to reverse miosis or achieve tachycardia, but to dry bronchial secretions and resolve bronchospasm to ensure pulmonary gas exchange.

1. Initial bolus (Adult): Administer 1 mg to 3 mg IV as a rapid bolus immediately. In children, administer 0.05 mg/kg.
2. Sequential doubling: If there is no clinical response (deep bronchorrhea persists), double the previous dose every 3 to 5 minutes (e.g., 2 mg, then 4 mg, then 8 mg, then 16 mg).
3. Maintenance infusion: Once atropinization is achieved (clear lungs, HR >80 bpm, dilated or normal pupils), calculate 10-20% of the total dose required to stabilize the patient and infuse it per hour via continuous intravenous route.

Security

Contraindications and Precautions

• There are no absolute contraindications in acute poisoning with life-threatening cholinergic origin.
• Precautions: May precipitate acute angle-closure glaucoma and induction of atropinic psychosis (central anticholinergic syndrome) if the effective maintenance dose is exceeded.

Adverse Effects (ADR)

• Frequent: Extreme dryness of skin and mucous membranes, mydriasis marked with photophobia, abolition of visual accommodation, reflex sinus tachycardia, acute urinary retention, severe constipation, delirium, psychomotor agitation.

Use in Special Populations

Pregnancy: Crosses the placenta and can induce tachycardia and loss of fetal heart rate variability. However, its administration should be prioritized due to the lethal nature of cholinergic poisoning. Compatible with breastfeeding with monitoring of anticholinergic effects in the infant.