What drugs cause pinpoint pupils?
Pinpoint pupils, medically termed miosis, refer to abnormally small, constricted pupils that do not dilate appropriately in low light. This symptom is a significant clinical clue and can be caused by various drugs and toxins. In this article, we will review several drugs that can cause pinpoint pupils.
Why Do Drugs Cause Pinpoint Pupils?
The size of our pupils is controlled by the interplay of two opposing branches of the autonomic nervous system: the sympathetic nervous system, which triggers the "fight or flight" response and dilates the pupils (mydriasis) to allow more light in for heightened awareness, and the parasympathetic nervous system, which governs the "rest and digest" functions and constricts the pupils. Increased parasympathetic output to the eye signals the sphincter pupillae, a circular muscle in the iris, to contract, leading to constriction of the pupil.
Opioids
The most well-known and clinically significant cause of pinpoint pupils is opioid use or overdose. Opioids—including both natural and synthetic varieties—activate mu-opioid receptors in the brain, which stimulate the parasympathetic nervous system and cause the muscles controlling the pupil to constrict. Common opioids associated with miosis include:
- Oxycodone (found in medications like OxyContin and Percocet)
- Hydrocodone (found in medications like Vicodin and Norco)
- Morphine
- Fentanyl (a powerful synthetic opioid)
- Codeine
- Buprenorphine (used in medications like Suboxone for opioid use disorder)
- Methadone
Pinpoint pupils are a classic sign of opioid toxicity or overdose, often accompanied by respiratory depression and decreased consciousness. However, it is important to note that while miosis is highly suggestive of opioid use, it is not exclusive to this class of drugs.
Antipsychotics
Some older and some second-generation antipsychotic medications have been associated with miosis, although this is a less common side effect compared to their other potential impacts. Antipsychotics that have been linked to pinpoint pupils include olanzapine, chlorpromazine, aripiprazole, and quetiapine. One potential cause is their ability to block α1‐adrenergic receptors.
Clonidine
While not typical at normal doses, the blood pressure medication clonidine has been known to cause pinpoint pupils in overdose situations. Other symptoms of overdose include slow heart rate, drowsiness, and irritability.
Barbiturates
Barbiturates are sedatives that are used to treat seizures, anxiety, and muscle spasms. This class of medications has been associated with changes in pupil size, especially during an overdose. This includes both mydriasis (larger pupils) and miosis (small pupils).
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Buspirone
Another medication that can cause pinpoint pupils is buspirone. Buspirone is an oral medication used to treat anxiety. It’s thought to cause this effect by activating 5-HT1A receptors in the central nervous system where they block sympathetic pathways.
Antiemetics
One study found that two antiemetics, droperidol and metoclopramide, decreased pupil size. The effects on the pupil were small.
Eye Drops
Certain eye drops called miotics can shrink the pupil. One example is pilocarpine, which is used to reduce eye pressure during procedures or exams. It is also used to treat an eye condition called presbyopia. Pilocarpine works by attaching to cholinergic receptors on ciliary and iris sphincter muscles, which makes the pupil smaller.
Organophosphate Pesticides and Nerve Agents
Organophosphate pesticides and chemical nerve agents inhibit acetylcholinesterase (an enzyme that breaks down acetylcholine), leading to excessive parasympathetic activity and pronounced miosis. Examples of organophosphate pesticides include:
- Chlorpyrifos
- Parathion
- Diazinon
- Dichlorvos
- Phosmet
- Fenitrothion
- Malathion
Exposure to these agents can result from agricultural chemicals or chemical warfare agents.
Cholinergic Medications
Cholinergic medications include drugs that directly act on muscarinic receptors, and those that prevent acetylcholine from being broken down. They are used for a wide range of conditions, such as Alzheimer's disease and myasthenia gravis. Examples include:
Pinpoint pupils are a potential side effect of these medications, but more common during an overdose.
Acute Management and Reversal Strategies
Rapid recognition and intervention is essential, especially in suspected opioid overdose or toxic exposures.
- Naloxone is the antidote for opioid-induced miosis, and atropine/pralidoxime can reverse organophosphate-induced pupil constriction.
- For medication-related miosis, withdrawal or switching medications may be needed; always consult a healthcare provider before altering therapy.
Emergency protocols for these situations are available from the FDA’s naloxone guidance and the CDC’s emergency preparedness resources.
Summary
Pinpoint pupils are most commonly associated with opioid intoxication, but several other drugs—including certain antipsychotics, antihypertensives, and toxins—can also cause this sign. Recognizing miosis and understanding its potential causes is important for timely diagnosis and treatment, especially in emergency and overdose situations.
References
- Adeyinka A, Muco E, Regina AC, et al. Organophosphates. [Updated 2023 Nov 12]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK499860/
- Bergeria, C. L., Huhn, A. S., Tompkins, D. A., Bigelow, G. E., Strain, E. C., & Dunn, K. E. (2019). The relationship between pupil diameter and other measures of opioid withdrawal during naloxone precipitated withdrawal. Drug and alcohol dependence, 202, 111–114. https://doi.org/10.1016/j.drugalcdep.2019.05.010
- Clonidine [package insert]. Updated 2022. Actavis Pharma, Inc. Accessed on June 13, 2025 at https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a842ab83-3531-44dd-a8a8-64dd89e87026
- Drug Enforcement Administration. n. d. Accessed on June 13, 2025 at https://www.dea.gov/factsheets/barbiturates
- Fanciullacci, M., Sicuteri, R., Alessandri, M., & Geppetti, P. (1995). Buspirone, but not sumatriptan, induces miosis in humans: relevance for a serotoninergic pupil control. Clinical pharmacology and therapeutics, 57(3), 349–355. https://doi.org/10.1016/0009-9236(95)90161-2
- Larson M. D. (2003). The effect of antiemetics on pupillary reflex dilation during epidural/general anesthesia. Anesthesia and analgesia, 97(6), 1652–1656. https://doi.org/10.1213/01.ANE.0000090011.19809.93
- Lin, R. C., et. al. 2010. Chapter 16 Retinal toxicity of systemic and topical medications. In: Retinal Pharmacotherapy. DOI: https://doi.org/10.1016/B978-1-4377-0603-1.00021-1
- MedlinePlus. 2024. Pilocarpine Ophthalmic. Accessed on June 13, 2025 at https://medlineplus.gov/druginfo/meds/a682874.html
- Mitchell, A. A., Lovejoy, F. H., & Goldman, P. (1976). Drug ingestions associated with miosis in comatose children. The Journal of pediatrics, 89(2), 303–305. https://doi.org/10.1016/s0022-3476(76)80474-x
- Mu, C., & Chen, L. (2024). Characteristics of eye disorders induced by atypical antipsychotics: a real-world study from 2016 to 2022 based on Food and Drug Administration Adverse Event Reporting System. Frontiers in psychiatry, 15, 1322939. https://doi.org/10.3389/fpsyt.2024.1322939
- Pakala RS, Brown KN, Preuss CV. Cholinergic Medications. [Updated 2023 Apr 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK538163/
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