Which medications can cause pupil constriction (miosis)?

Medications That Cause Pupil Constriction (Miosis)

Opioids, topical miotics (particularly pilocarpine and other parasympathomimetics), and certain glaucoma medications are the primary pharmacologic agents that cause pupillary constriction.

Opioid Analgesics

Opioids are among the most potent miotic agents and produce characteristic pinpoint pupils through direct central nervous system effects:

• All opioid agonists cause miosis by direct action on the visceral nuclei of the oculomotor nuclear complex in the brainstem, increasing pupilloconstrictor neuron activity 1, 2, 3
• Pinpoint pupils are a classic sign of opioid overdose, though they are not pathognomonic—pontine hemorrhage or ischemic stroke can produce identical findings 1, 2
• Remifentanil and buprenorphine specifically cause miosis even in total darkness, with the effect persisting throughout the duration of opioid action 1, 2
• Methadone produces peak miosis approximately 90 minutes after oral administration, best detected under moderately dim lighting conditions (4-16 foot-lamberts) 4
• Miosis correlates strongly with response to naloxone in suspected opioid overdose, though many factors affect pupil size and first aid providers may not reliably identify miosis 5
• Marked mydriasis rather than miosis may occur in severe opioid overdose due to hypoxia, which is an important clinical pitfall 1, 2

Topical Parasympathomimetic Agents (Miotics)

These medications cause pupillary constriction by stimulating the iris sphincter muscle:

• Pilocarpine 1.25% (Vuity) is FDA-approved for daily treatment of presbyopia and induces bilateral miosis by stimulating ciliary muscle contraction, creating a "pinhole" effect that improves near visual acuity 6
• All topical miotic agents used in glaucoma therapy produce bilateral pupil constriction and are part of first-line medical management for acute angle-closure glaucoma 6, 7
• Pilocarpine causes dose-dependent miosis that can be enhanced when combined with other miotic mechanisms 8
• A dilated fundus examination is mandatory before initiating pilocarpine therapy because miotics can precipitate retinal tears or detachment in eyes with pre-existing retinal pathology 6

Glaucoma Medications

Multiple classes of glaucoma medications are associated with miosis:

• Parasympathomimetic eye drops (including pilocarpine and other cholinergic agonists) are used for rapid intraocular pressure reduction in acute angle-closure glaucoma 7
• Epinephrine and other glaucoma medications, especially miotics, are associated with medication-induced mucous membrane pemphigoid and chronic conjunctivitis 5
• Timolol and other topical glaucoma agents can produce ocular mucous membrane pemphigoid-like disease when used chronically 5

Additive Miotic Effects

• Dapiprazole (alpha-adrenergic antagonist) combined with pilocarpine produces additive miotic effects because dapiprazole paralyzes the dilator muscle while pilocarpine stimulates the sphincter muscle, working through complementary mechanisms 8
• Co-administration of multiple miotic agents induces significantly faster pupillary constriction than either drug alone, which may be useful in preventing acute angle-closure glaucoma attacks in patients with anatomically narrow angles 8

Critical Clinical Pitfalls

• Never attribute pinpoint pupils solely to opioid toxicity without excluding neurological emergencies: patients presenting with pinpoint pupils plus altered mental status, progressive loss of consciousness, or focal neurological deficits require immediate neuroimaging (contrast-enhanced MRI with MR-angiography or CT-angiography) to exclude pontine hemorrhage or other structural lesions 6
• Consensual pupillary responses occur with unilateral drug administration: mydriatic drugs instilled in one eye can cause dose-dependent miosis in the untreated fellow eye under certain lighting conditions, though this effect is not universal 9
• Lighting intensity dramatically affects pupil diameter measurement: pupil diameter decreases approximately 1.0 mm with each log unit increase in lighting intensity, and measurements differ by an average of 0.35 mm between monocular and binocular viewing 4
• Anticholinergic medications can precipitate angle-closure attacks in susceptible patients through pupillary dilation, including systemic medications with anticholinergic effects (phenothiazines, ipratropium bromide, salbutamol-containing inhalers) and topical mydriatic eye drops 5