Medications Causing Dilated Fixed Pupils
Anticholinergic medications are the primary drug class causing dilated and fixed pupils, with common culprits including antihistamines (diphenhydramine), anticholinergics (scopolamine, atropine), tricyclic antidepressants, phenothiazines (promethazine, prochlorperazine), and central nervous system stimulants (cocaine, amphetamines, methylphenidate). 1, 2, 3
Anticholinergic Toxicity: Classic Presentation
The anticholinergic syndrome presents with both central and peripheral manifestations. Peripheral toxicity is characterized by markedly dilated and fixed pupils (mydriasis), along with tachycardia, hot dry flushed skin, urinary retention, diminished gastrointestinal motility, and decreased secretions. 2, 4 Central toxic effects include anxiety, delirium, disorientation, hallucinations, hyperactivity, and in severe cases, seizures or coma. 2
Specific Drug Classes and Agents
Anticholinergic Medications
- Scopolamine (centrally acting anticholinergic) causes pupillary dilation along with blurred vision, dry mouth, urinary retention, and sedation. 1
- Atropine and other belladonna alkaloids directly produce anticholinergic syndrome with fixed dilated pupils. 2
- Diphenhydramine and other antihistamines have strong anticholinergic effects causing mydriasis, sedation, and confusion, particularly problematic in older adults. 5, 3
Psychotropic Medications
- Tricyclic antidepressants have high anticholinergic properties that can induce delirium and dilated pupils. 5, 2, 3
- Phenothiazines (promethazine, prochlorperazine, chlorpromazine) possess anticholinergic effects causing pupillary dilation. 6, 5, 2
CNS Stimulants
- Cocaine, methylphenidate, and amphetamines cause pupillary dilation through sympathomimetic mechanisms. 3
Clinical Recognition
In acute anticholinergic poisoning, patients present with classic signs: tachycardia, hot dry flushed skin, markedly dilated and fixed pupils, and pronounced delirium with violent agitation. 4 The combination of mydriasis with altered mental status, hyperthermia, and dry mucous membranes should immediately raise suspicion for anticholinergic toxicity. 2, 4
Critical Warnings
Anticholinergic agents can precipitate acute angle-closure glaucoma in susceptible individuals with narrow iridocorneal angles. 1, 7 Patients with primary angle-closure suspect should be warned that these medications could cause pupil dilation and induce acute angle-closure. 1
Multiple anticholinergic drugs create "anticholinergic burden" that adversely affects cognition, functional status, and activities of daily living, with particularly severe effects in older adults. 5
Treatment Considerations
Physostigmine salicylate is the specific antidote for anticholinergic toxicity, producing dramatic reversal of symptoms including pupillary constriction within 15-20 minutes of intravenous administration. 2, 4 The duration of action is relatively short (45-60 minutes), so repeated dosing may be necessary. 2 In cases where physostigmine is unavailable due to national shortages, rivastigmine (oral or transdermal) represents a reasonable alternative. 8