Which medications can cause pinpoint pupils (miosis)?

Medications That Cause Pinpoint Pupils (Miosis)

Opioid Analgesics

Opioid medications are the most clinically significant cause of pinpoint pupils, producing miosis through direct action on brainstem opioid receptors even in total darkness. 1, 2

Mechanism and Clinical Presentation

• All full opioid agonists cause miosis by direct action on mu-opioid receptors in the brainstem, independent of lighting conditions 1, 2
• Pinpoint pupils are a hallmark sign of opioid overdose, though not pathognomonic (pontine lesions from hemorrhage or ischemia can produce similar findings) 1, 2
• Marked mydriasis (pupil dilation) rather than miosis may occur in severe opioid overdose due to hypoxia, which is an important clinical caveat 1, 2

Specific Opioid Agents

The following opioids produce dose-dependent miosis:

• Morphine causes sustained pupillary constriction with peak effect within 2 minutes of IV administration 1, 3, 4
• Hydromorphone produces miosis through the same mu-opioid receptor mechanism as morphine 2
• Codeine causes approximately 26% decrease in pupil diameter after IV administration 4
• Heroin, oxycodone, oxymorphone, and hydrocodone all produce systematic decreases in pupillary size 3
• Methadone produces peak miosis approximately 90 minutes after oral administration, best detected under moderately dim lighting (4-16 foot-lamberts) 5
• Tramadol shows delayed miotic effect, with significant pupillary reduction beginning 150 minutes after administration 4

Clinical Monitoring Considerations

• Opioid-induced miosis decreases both pupil diameter and the velocity of pupillary constriction to light stimuli 3
• The velocity of pupillary redilation after light stimulus is also decreased by opioids 3
• Pupil diameter measurements can serve as an objective index of opioid effects and may help monitor the central effects of opioid therapy 5, 4

Topical Miotic Agents

Pilocarpine

• Pilocarpine 1.25% (Vuity) is FDA-approved for daily treatment of presbyopia and produces bilateral miosis through ciliary muscle contraction 6
• Pilocarpine acts as a parasympathomimetic agent, creating a "pinhole" effect that improves near visual acuity 6
• A dilated retinal examination is mandatory before initiating pilocarpine due to risk of retinal tears or detachment in patients with pre-existing retinal pathology 6

Other Topical Miotics

• Topical miotic agents used for glaucoma treatment produce bilateral pupil constriction 7
• Parasympathomimetics are used in acute angle-closure glaucoma management as part of first-line medical therapy to lower intraocular pressure 8

Antimuscarinic Agents for Myopia Control

While these agents are used therapeutically for myopia control rather than causing problematic miosis, they warrant mention:

• Atropine in various concentrations (0.01%, 0.025%, 0.05%, 0.1%, 0.5%) is used to slow myopia progression in children, though higher concentrations cause photosensitivity and require bifocals for near work 9
• Cyclopentolate 1% administered nightly has been evaluated for myopia control 9
• Pirenzepine 2% ophthalmic gel has been studied as a selective muscarinic antagonist for myopia progression 9

Critical Clinical Pitfalls

• In patients presenting with pinpoint pupils plus altered mental status, progressive loss of consciousness, or focal neurological deficits, immediate neuroimaging (contrast-enhanced MRI with MR-angiography or CT-angiography) is required to rule out pontine hemorrhage or other structural lesions 7
• Do not assume pinpoint pupils always indicate opioid toxicity—consider pontine stroke, organophosphate poisoning, and other neurological emergencies 7, 1, 2
• Severe hypoxia from opioid-induced respiratory depression can paradoxically cause mydriasis rather than miosis, which may mislead clinicians away from the diagnosis of opioid overdose 1, 2