What are the side effects of atropine?

Side Effects of Atropine

Atropine causes dose-dependent anticholinergic side effects ranging from common peripheral effects (dry mouth, blurred vision, tachycardia) to potentially life-threatening central nervous system toxicity and cardiovascular complications, with paradoxical bradycardia occurring at low doses (<0.5 mg) and serious arrhythmias possible at higher doses. 1, 2

Dose-Dependent Paradoxical Effects

Low-dose atropine (<0.5 mg IV or non-IV routes) can paradoxically worsen bradycardia and depress AV conduction rather than improve it, due to central reflex vagal stimulation or peripheral parasympathomimetic effects on the heart. 1, 3 This is a critical pitfall when treating bradycardia—always use at least 0.5 mg IV to avoid this paradoxical response.

Common Peripheral Anticholinergic Effects

The most frequently encountered side effects result from antimuscarinic blockade and include:

• Dry mouth (xerostomia) is the most common complaint 2, 4
• Blurred vision and photophobia from pupillary dilation and cycloplegia 2
• Tachycardia from vagal blockade, which can be particularly dangerous in patients with coronary artery disease by increasing myocardial oxygen demand 5, 2
• Anhidrosis (inability to sweat) leading to heat intolerance 2
• Constipation and urinary retention from smooth muscle relaxation 2

Gastrointestinal Effects

• Delayed gastric emptying (gastroparesis) can occur even with aerosolized atropine, with gastric half-emptying time prolonged from 65 minutes to 112 minutes in one study 4
• Paralytic ileus may develop with repeated or high doses 2
• Exacerbation of gastroesophageal reflux has been reported 2

Central Nervous System Toxicity

Repeated administration or toxic doses produce serious CNS effects that require careful monitoring:

• Hallucinations and fever are warning signs of CNS toxicity 1, 5
• Restlessness, tremor, and fatigue occur with larger doses 2
• Delirium, confusion, and agitation represent moderate toxicity 2, 6, 7
• Locomotor difficulties, depression, and ultimately medullary paralysis can progress to death in severe cases 2
• Central anticholinergic syndrome can present with stroke-like symptoms and varied severity from mild cognitive impairment to severe coma 6, 7

Cardiovascular Complications

Beyond the expected tachycardia, serious cardiac effects include:

• Sinus tachycardia that increases myocardial ischemia, particularly dangerous in acute myocardial infarction where it can extend infarct size 1, 5
• Ventricular tachycardia and ventricular fibrillation rarely occur after IV administration 1
• Re-entry intra-atrial arrhythmias or sinus pauses in rare cases 3
• Paradoxical cardiac block or sinus arrest in 20% of heart transplant patients receiving standard doses 3
• Circulatory collapse with large toxic doses, leading to blood pressure decline and respiratory failure 2

Hypersensitivity Reactions

• Allergic reactions are rare but include local manifestations (especially with ophthalmic drops) and systemic anaphylaxis 2, 8
• Serious skin rashes have been observed occasionally 2
• True allergy prevalence is unknown because most reactions are mild and testing is not routinely performed 8

Special Population Considerations

• Elderly patients are at higher risk for CNS side effects including central anticholinergic syndrome 7
• Patients with coronary artery disease face significant risk from atropine-induced tachycardia increasing myocardial oxygen demand 5
• Patients on tricyclic antidepressants have higher baseline heart rates but do not show exaggerated cardiac responses to atropine 9

Ophthalmic Route Systemic Absorption

Even topical ophthalmic atropine at normal doses can cause systemic anticholinergic toxicity through absorption, potentially resulting in stroke-like symptoms that may be overlooked if the ophthalmic route is not considered. 6 This represents an important diagnostic pitfall.

Management of Toxicity

• Physostigmine is the antidote for severe central anticholinergic syndrome and can completely reverse toxidrome symptoms 6, 7
• Supportive care with prompt recognition and discontinuation of atropine is essential 7
• For patients with proven atropine allergy, glycopyrrolate combined with benzodiazepines or scopolamine provides an alternative anticholinergic regimen 8