Atropine

Atropine: The Anesthesiologist's Anticholinergic Mainstay

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Introduction

Atropine is a naturally occurring tropane alkaloid derived from the deadly nightshade plant (Atropa belladonna). As the prototypical anticholinergic agent, it is a fundamental drug in anesthesia practice. Its primary roles are to counteract excessive vagal stimulation (bradycardia) and to suppress secretions. While seemingly simple, its dose-dependent effects and potential for serious side effects demand a thorough understanding.

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1. Chemical Structure

Atropine is a secondary amine and a tropane alkaloid. Crucially, it is a tertiary amine, which makes it relatively lipophilic. This property allows it to readily cross the blood-brain barrier, leading to central nervous system (CNS) effects, a key differentiator from other anticholinergics like glycopyrrolate.

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2. Mechanism of Action (MOA)

Atropine is a competitive antagonist at muscarinic acetylcholine receptors. It does not block nicotinic receptors (e.g., at the neuromuscular junction or autonomic ganglia). By blocking acetylcholine from binding to muscarinic receptors, it effectively "paralyzes" the parasympathetic nervous system.

It non-selectively blocks all five muscarinic receptor subtypes (M1-M5), leading to a wide range of effects:

• Heart (M2): Blocks vagal effects, leading to an increase in heart rate and conduction.
• Smooth Muscle (M3): Causes relaxation of smooth muscle in the bronchi, GI tract, biliary tract, and urinary bladder.
• Glands (M3): Inhibits secretions from salivary, sweat, and bronchial glands.
• Eye (M3): Causes mydriasis (pupil dilation) and cycloplegia (paralysis of accommodation).
• CNS (M1): At higher doses, produces sedation, confusion, and delirium.

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3. Pharmacokinetics

• Onset: Rapid with IV administration (< 1 minute). Slower with IM (15-30 minutes) and SC (20-30 minutes).
• Distribution: Widely distributed throughout the body, including the CNS.
• Metabolism: Approximately 50% is metabolized by the liver via hydrolysis. The rest is excreted unchanged in the urine.
• Duration of Action: The IV dose lasts for about 30-60 minutes. The effects on the heart (tachycardia) are shorter-lived than the effects on secretions or the eye.

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4. Pharmacodynamics (Dose-Dependent Effects)

The clinical response to atropine is highly dependent on the dose, which is a critical concept for trainees.

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5. Clinical Uses in Anesthesia

1. Treatment of Bradycardia: The primary use. It is the first-line drug for symptomatic sinus bradycardia, especially when caused by increased vagal tone (e.g., from fentanyl, succinylcholine, traction on extraocular muscles (oculocardiac reflex), or peritoneal traction).
2. Pre-medication for Reversal: Used to prevent the muscarinic side effects (bradycardia, bronchorrhea, salivation) of the acetylcholinesterase inhibitor neostigmine when reversing non-depolarizing neuromuscular blockade.
3. Reduction of Secretions: Used as a pre-medication to dry secretions, particularly for procedures involving the airway (e.g., awake fiberoptic intubation, bronchoscopy) to improve visualization and prevent laryngospasm.
4. Prevention of Bradycardia: May be given prophylactically before administering drugs known to cause bradycardia (e.g., succinylcholine in children).
5. Treatment of Organophosphate Poisoning: Used in massive doses to reverse life-threatening muscarinic effects.

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6. Dosage

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7. Adverse Effects & Complications

• Cardiovascular:
  • Tachycardia: Can cause or worsen myocardial ischemia in patients with coronary artery disease by increasing heart rate and myocardial oxygen demand.
  • Arrhythmias: Can precipitate atrial fibrillation or ventricular tachyarrhythmias in susceptible individuals.
• CNS:
  • Central Anticholinergic Syndrome: Confusion, agitation, delirium, and hallucinations, especially in the elderly and at higher doses.
• Other:
  • Xerostomia: Dry mouth.
  • Mydriasis and Cycloplegia: Blurred vision, photophobia.
  • Urinary Retention: Due to relaxation of the bladder detrusor muscle.
  • Hyperthermia: Inhibits sweating, impairing the body's ability to cool itself.
• Contraindications/Cautions:
  • Narrow-Angle Glaucoma: Can precipitate an acute attack by causing mydriasis and closing the filtration angle.
  • Tachyarrhythmias and Unstable Angina.
  • Obstructive Uropathy (e.g., BPH).

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8. Special Section: Atropine vs. Glycopyrrolate - The Trainee's Dilemma

A common point of confusion for trainees is when to use atropine versus its more modern cousin, glycopyrrolate. The choice is driven by their key pharmacological differences.

Rule of Thumb for Trainees:

• Need to treat a slow heart rate NOW? -> Atropine (IV).
• Need to prevent bradycardia from reversal or dry secretions for an airway procedure? -> Glycopyrrolate (IV).
• Patient is elderly or having brain surgery? -> Glycopyrrolate is safer to avoid CNS effects.