Which group of medications causes pupillary constriction?

October 10, 2025 •

4 min read

The size of our pupils is regulated by the autonomic nervous system, and approximately 55% of patients in one ICU study showed smaller pupils when receiving fentanyl, an opioid. A notable side effect of several drug classes is pupillary constriction (miosis), and understanding which group of medications causes pupillary constriction is critical for accurate diagnosis and clinical management, especially in overdose situations.

Quick Summary

Several drug classes, such as opioids, miotics, and acetylcholinesterase inhibitors, cause miosis by influencing the parasympathetic nervous system. This article explores these medications, their mechanisms, and why this involuntary reaction to certain drugs is a significant clinical sign.

Key Points

Opioids and Miosis: Opioid analgesics like fentanyl and morphine are a primary cause of pupillary constriction (miosis) by stimulating the parasympathetic nervous system.
Miotics as Treatment: Miotics, such as pilocarpine, are eye drops specifically prescribed to cause miosis, primarily for treating glaucoma and presbyopia.
Anticholinesterase Effects: Medications like donepezil and toxins like organophosphate pesticides inhibit the enzyme that breaks down acetylcholine, leading to increased levels of this neurotransmitter and subsequent miosis.
Miosis as a Clinical Marker: The presence of pinpoint pupils is a key diagnostic indicator for healthcare providers, particularly in recognizing opioid overdose.
Various Drug Classes Involved: In addition to opioids and miotics, certain antipsychotics, blood pressure medications (clonidine), and anxiolytics can also cause miosis as a side effect.
Different Mechanisms, Same Outcome: While these medication groups all lead to miosis, their mechanisms vary. Some act directly on receptors, while others block enzyme activity or indirectly alter nervous system balance.

The pupils, the black circular openings in the center of the iris, automatically adjust in size to control the amount of light entering the eye. This adjustment is controlled by the autonomic nervous system through two opposing sets of muscles in the iris: the sphincter pupillae (which constricts the pupil) and the dilator pupillae (which dilates it). The parasympathetic nervous system, activated during "rest and digest" functions, signals the sphincter pupillae to contract, causing pupillary constriction (miosis). Several medications can trigger or enhance this parasympathetic response, leading to noticeably smaller pupils.

Opioid Analgesics

Opioids are one of the most well-known and clinically significant groups of medications that cause pupillary constriction. This class includes both prescription pain relievers and illicit substances, such as:

Morphine
Codeine
Fentanyl
Oxycodone
Hydrocodone

Opioids cause miosis by acting on mu-opioid receptors in the brain, which in turn stimulates the parasympathetic nervous system. Specifically, they suppress the inhibitory tract of a key brainstem nucleus (the Edinger-Westphal nucleus), resulting in an excitatory response that constricts the pupil. This effect is often dose-dependent, meaning higher concentrations of the drug can cause more pronounced miosis. Pinpoint pupils are a classic and highly suggestive sign of opioid toxicity or overdose, often appearing alongside other symptoms like respiratory depression and decreased consciousness.

Miotics (Cholinergic Agonists)

Miotics are a group of drugs specifically designed to cause pupillary constriction for medical purposes, primarily in ophthalmology. These agents mimic the action of acetylcholine, the neurotransmitter of the parasympathetic nervous system.

Direct-acting miotics: These bind directly to muscarinic receptors on the iris sphincter muscle to cause contraction.

Pilocarpine: Available as eye drops, it is used to treat glaucoma, ocular hypertension, and recently, presbyopia (age-related farsightedness). By constricting the pupil, it increases the eye's depth of focus and enhances the drainage of fluid to reduce intraocular pressure.
Carbachol: Also used in eye surgery and for glaucoma treatment.

Acetylcholinesterase Inhibitors

This group of medications works indirectly by inhibiting the enzyme acetylcholinesterase, which is responsible for breaking down acetylcholine in the synaptic cleft. By blocking this enzyme, the concentration of acetylcholine increases, leading to a prolonged and enhanced parasympathetic response, including miosis.

Donepezil and Physostigmine: These are examples of acetylcholinesterase inhibitors. Physostigmine is sometimes used to reverse the effects of anticholinergic drug toxicity, and its side effects can include miosis. Donepezil is used to treat Alzheimer's disease.
Organophosphate Toxins: Highly potent acetylcholinesterase inhibitors, such as those found in certain pesticides and chemical nerve agents, can cause extreme, pronounced miosis upon exposure. This is a key diagnostic sign of poisoning.

Other Medications and Substances

Beyond the primary culprits, several other medication classes can cause miosis as a side effect, though the effect is often less pronounced or occurs only in overdose situations.

Antipsychotics: Some older and newer generation antipsychotics, including olanzapine and quetiapine, can cause miosis. This effect is thought to be related to their ability to block alpha-adrenergic receptors, which indirectly enhances the parasympathetic response.
Antihypertensives: The blood pressure medication clonidine has been known to cause miosis, especially in overdose scenarios.
Barbiturates: Sedatives like barbiturates can also affect pupil size, with miosis being a potential effect, especially during an overdose.
Anxiety Medications: Some benzodiazepines, such as diazepam (Valium), and other anxiolytics like buspirone can lead to miosis.

Comparison of Medication Groups Causing Miosis


Drug Group	Primary Mechanism	Key Examples	Clinical Use	Significance of Miosis
Opioid Analgesics	Stimulates parasympathetic nervous system via mu-opioid receptors	Morphine, Fentanyl, Oxycodone	Pain relief, anesthesia	Overdose marker; diagnostic sign of toxicity
Miotics (Cholinergic Agonists)	Directly activates muscarinic receptors on iris sphincter	Pilocarpine, Carbachol	Glaucoma, presbyopia, diagnostic tests	Therapeutic goal; desired effect
Acetylcholinesterase Inhibitors	Inhibits the enzyme that breaks down acetylcholine	Physostigmine, Donepezil	Alzheimer's, reversal of anticholinergics	Side effect; prominent in toxicity
Antipsychotics	Blocks alpha-adrenergic receptors	Olanzapine, Quetiapine	Mental health disorders	Less common side effect

Conclusion

In summary, pupillary constriction (miosis) is a physiological response caused by a diverse range of medications and substances. The most common and clinically significant culprits are opioids, which induce miosis by exciting the parasympathetic nervous system. Other groups, such as miotics used in ophthalmology and acetylcholinesterase inhibitors, also cause this effect, but through slightly different mechanisms. For healthcare professionals, recognizing medication-induced miosis is crucial for diagnosing drug-related issues, ranging from expected side effects in glaucoma treatment to potentially life-threatening opioid overdoses. It serves as an important clinical sign that points towards the action of a particular group of medications on the nervous system. For individuals on these medications, awareness of these potential effects can help in monitoring their treatment and identifying any adverse reactions.

Authoritative Link: Drugs.com: What drugs cause pinpoint pupils?

Frequently Asked Questions

Miosis is the medical term for pupillary constriction, which means the pupil becomes very small. Mydriasis is the opposite effect, where the pupil becomes dilated or enlarged.

No, while pinpoint pupils are a classic sign of opioid overdose, other medical conditions (like Horner's syndrome or pontine lesions) and medications (like miotic eye drops) can also cause miosis. Therefore, it is not a definitive sign on its own.

Opioids cause pupillary constriction by activating mu-opioid receptors in the brainstem, which stimulates the parasympathetic nervous system. This triggers the sphincter muscle in the iris to contract, making the pupil smaller.

Certain over-the-counter medications, like some antihistamines (e.g., diphenhydramine), can have anticholinergic properties at lower doses that typically cause dilation, but some have been associated with miosis as a side effect. However, this is less common than with prescription drugs like opioids.

Doctors may intentionally constrict a patient's pupils using miotic eye drops to treat conditions such as glaucoma or presbyopia. In glaucoma, it helps to increase the drainage of fluid to reduce pressure, and for presbyopia, it increases depth of focus.

Miotics are direct-acting agents that bind directly to receptors to cause constriction. Acetylcholinesterase inhibitors act indirectly by preventing the breakdown of the neurotransmitter acetylcholine, increasing its concentration and enhancing its effects.

Yes, several factors can cause miosis, including exposure to bright light, the normal aging process, certain neurological conditions like Horner's syndrome, brain injuries, and eye injuries.