Atropine

Mechanism

Mechanism of Action

Reversible and highly selective competitive antagonist of all muscarinic cholinergic receptor subtypes (M₁, M₂, M₃, M₄, M₅), with no relevant affinity for nicotinic receptors. By selectively binding to the muscarinic receptor, it blocks the action of acetylcholine. In cardiac conduction tissue, it blocks M₂ receptors in the sinus and atrioventricular node, which counteracts basal vagal tone, significantly increasing heart rate and AV conduction velocity. In the eye, it blocks the M₃ receptors of the iris sphincter muscle and the ciliary muscle, inducing persistent mydriasis and cycloplegia. Likewise, it powerfully inhibits the secretions of the bronchial, salivary and sweat glands.

Pharmacokinetics

Key Pharmacokinetics

• Routes: Intravenous, intramuscular, subcutaneous, ophthalmic, endotracheal.
• Structure: Natural tertiary amine that easily crosses the blood-brain barrier, which can induce adverse effects and toxicity at the CNS level (especially in elderly patients).
• Metabolism: Partially hepatic through hydrolysis to tropine and tropic acid.
• Elimination half-life: 2 to 4 hours in adults.
• Excretion: Renal, eliminating 30-50% of the unchanged drug directly in the urine.

Indicators and dose

Approved and Off-label Indications

Approved: Treatment of acute symptomatic sinus bradycardia (including advanced cardiovascular life support); resuscitation in the context of cardiac arrest due to transient asystole; specific antidote against acute poisoning by organophosphate insecticides, carbamates or nerve gases; anesthetic premedication to inhibit extreme salivation and prevent intraoperative reflex bradycardia; ophthalmic induction of mydriasis and therapeutic cycloplegia.

Off-label: Symptomatic control of refractory drooling in severe pediatric or adult neurological pathology.

Dosage and Adjustments

Acute Symptomatic Bradycardia (IV): Administer 0.5 to 1.0 mg IV every 3-5 minutes as needed. Maximum recommended total dose of 3.0 mg (complete vagal block achieved). Doses less than 0.5 mg are inadvisable due to the paradoxical risk of inducing transient bradycardia due to the preferential blockade of central presynaptic muscarinic receptors.

Organophosphate Intoxication: 1 to 2 mg IV in initial boluses repeated continuously every 5 to 15 minutes until complete atropinization and reversal of airway edema (disappearance of bronchial secretions and wheezing) is achieved.

Renal/hepatic adjustment: No dosimetric adjustment guidelines have been established in organ failure; Monitoring of urinary emptying is recommended.

Security

Contraindications

Absolute: Untreated or primary narrow angle glaucoma (muscarinic blockade and mydriasis associate imminent risk of acute angle closure with irreversible blindness); low obstructive uropathy or severe active urinary retention.

Relative: Sinus tachycardia, decompensated atrial fibrillation, myasthenia gravis, severe ulcerative colitis (risk of toxic megacolon).

Adverse Effects (ADR)

Common: Severe xerostomia, blurred vision of close objects, pronounced photophobia, persistent pupillary mydriasis, initial urinary retention, refractory constipation, facial flushing due to inhibition of sweating.

Serious: Dangerous tachycardia cardiac arrhythmias (e.g., ventricular tachycardia), acute atropinic delirium (characterized by visual hallucinations, severe confusion, and psychomotor agitation), severe hyperthermia caused by blockage of thermal dissipation of sweat.

Interactions

Antihistamines, tricyclic antidepressants, phenothiazines: Very pronounced additive anticholinergic effect, exponentially increasing the risk of delirium, urinary retention and acute adynamic ileus.

Metoclopramide, domperidone: Decreases the gastrointestinal prokinetic effect due to direct antagonism of motility.

Pregnancy and Breastfeeding

FDA Classification: Category C. Crosses the placenta and can induce transient fetal sinus tachycardia. It is excreted in small quantities in breast milk and can partially suppress natural lactation due to a decrease in the hormonal secretory stimulus.

Acute anticholinergic (atropinic) syndrome

Overdose of atropine or other drugs with antimuscarinic activity induces a systemic toxic syndrome that is described mnemonically in the classic clinical literature as follows:

• "Blind as a mole": Extreme mydriasis with abolition of the photomotor reflex and blurred vision.
• "Red like a tomato": Intense facial and body skin flush due to compensatory reflex vasodilation.
• "Dry as a bone": Severe anhidrosis of the skin and mucous membranes with xerostomia and intense thirst.
• "Hot as a hare": Extreme hyperthermia due to abolition of the thermoregulatory mechanisms of sweat.
• "Crazy as a goat": Acute delirium, hallucinations, psychomotor agitation and spatial disorientation.

Specific treatment for severe life-threatening compromise is carried out with the administration of Physostigmine (salicylate), a tertiary amine cholinesterase inhibitor capable of crossing the blood-brain barrier.