Atropine

Chemical Structure & Physical Properties

Mechanism of Action

Pharmacological Effects by System

Cardiovascular

• Blocks M2 receptors at the SA node → tachycardia (most potent anticholinergic for this)
• Promotes conduction through the AV node → shortens PR interval
• Reverses vagally-mediated bradycardia (baroreceptor reflex, oculocardiac reflex, peritoneal traction)
• Paradoxical bradycardia may occur with small IV doses (<0.4 mg) - mechanism unclear
• Large doses can cause atrial arrhythmias and nodal rhythms
• Dilates cutaneous vessels at large doses (atropine flush)
• Caution: Patients with CAD may not tolerate increased myocardial O2 demand from tachycardia

Respiratory

• Inhibits secretions from nose to bronchi (antisialagogue, antitussive)
• Relaxes bronchial smooth muscle → bronchodilation, reduces airway resistance, increases anatomical dead space
• Effects more pronounced in COPD and asthma
• Derivative ipratropium bromide (quaternary ammonium - no systemic absorption) is used in metered-dose inhalers for bronchospasm

Central Nervous System

• Minimal CNS effects at usual doses despite crossing the BBB
• At toxic doses: excitatory reactions, restlessness, hallucinations
• Associated with mild postoperative memory deficits
• Reversed by physostigmine (cholinesterase inhibitor that crosses the BBB)

Gastrointestinal

• Markedly reduces salivation
• Reduces gastric secretions (at larger doses)
• Decreases intestinal motility and peristalsis → prolonged gastric emptying
• Reduces lower esophageal sphincter pressure
• Does NOT prevent aspiration pneumonia

Ophthalmic

• Mydriasis (pupillary dilation) - especially with topical use
• Cycloplegia (loss of accommodation to near vision)
• Atropine eye drops last 7-14 days (much longer than tropicamide)
• Risk of precipitating acute angle-closure glaucoma

Genitourinary

• Smooth muscle relaxation → decreased ureter and bladder tone
• May cause urinary retention, especially in men with prostatic hypertrophy

Thermoregulation

• Inhibits sweat glands → atropine fever (hyperthermia)

Indications & Clinical Uses

Dosing (Adults and Pediatrics)

• Adult: 0.5-1 mg IV q5 min; max total 3 mg
• Child: 0.02 mg/kg IV/IO/IM q5 min x 2-3 doses; max single dose 0.5 mg (child), 1 mg (adolescent)
• ET tube (child): 0.04-0.06 mg/kg, diluted in 1-2 mL NS

• Neonate: 0.01-0.02 mg/kg IV/IM
• Child: 0.02 mg/kg IV/IM; max 0.5 mg
• Adult: 0.5 mg IV/IM

• <6 mo (<7 kg): 0.25 mg
• 6 mo-4 yr (7-18 kg): 0.5 mg
• 4-10 yr (18-41 kg): 1 mg

• 10 yr and adult (>41 kg): 2 mg

• Mild symptoms: 1 dose; Severe symptoms: up to 3 doses in rapid succession

Available Formulations

Side Effects (Anticholinergic Toxidrome)

• Dry mouth, dry skin (anhidrosis)
• Blurred vision, mydriasis
• Flushing (atropine flush/fever)
• Hyperthermia
• Tachycardia
• CNS: dizziness, restlessness, hallucinations, delirium
• Constipation, urinary retention

Contraindications

• Glaucoma (narrow-angle) - may precipitate acute attack
• Obstructive uropathy / prostatic hypertrophy - risk of urinary retention
• Tachycardia / thyrotoxicosis (except in life-threatening muscarinic poisoning)
• Patients with CAD (tachycardia increases O2 demand)
• Heart transplant patients - atropine is ineffective for sinus bradycardia due to absence of vagal reinnervation

Comparison with Other Anticholinergics

Key Clinical Pearls

1. Organophosphate poisoning: Atropine reverses muscarinic effects (SLUDGE: Salivation, Lacrimation, Urination, Defecation, GI upset, Emesis) but NOT the nicotinic-mediated muscle weakness. Add pralidoxime (2-PAM) to reactivate acetylcholinesterase.
2. Heart transplant: Atropine does NOT work because the transplanted heart lacks vagal innervation - use epinephrine or pacing instead.
3. Small IV doses (<0.4 mg): Can cause paradoxical bradycardia - always use adequate doses.
4. Neonatal bradycardia: Routine use is no longer recommended. The old "minimum 0.1 mg" rule no longer applies and can overdose smaller patients.
5. Physostigmine reverses central anticholinergic toxicity (physostigmine crosses the BBB; neostigmine does not).

Atropine - Indications, Contraindications & Mechanism of Action

Mechanism of Action

Muscarinic Receptor Subtypes Blocked

The clinical response depends on baseline vagal tone - patients with high vagal tone show more pronounced responses.

Indications

1. Symptomatic Bradycardia

• Reverses: vagal reflex bradycardia (oculocardiac reflex, peritoneal traction, baroreceptor reflex), sinus bradycardia, AV nodal block

2. Organophosphate / Nerve Agent Poisoning

• Large, repeated doses required until bronchial secretions terminate
• Combined with pralidoxime (2-PAM) to reactivate acetylcholinesterase

3. Preoperative Antisialagogue

4. Reversal of Neuromuscular Blockade (as pretreatment)

5. Ophthalmic Uses

• Mydriasis (pupillary dilation) for fundal examination
• Cycloplegia (paralysis of accommodation) for refraction in children
• Uveitis - reduces pain by relaxing ciliary muscle and iris sphincter
• Longer duration (7-14 days) than tropicamide, so preferred for therapeutic rather than diagnostic use

6. Bronchospasm (via nebulizer)

7. Preintubation in Children

8. Anticholinergic Antidote

Contraindications

Note: Glaucoma, uropathy, tachycardia, and thyrotoxicosis are relative contraindications - they are overridden in life-threatening muscarinic poisoning where benefit outweighs risk.

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