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.

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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).

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

These chemicals 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:

• Neostigmine
• Donepezil
• Galantamine

Pinpoint pupils are a potential side effect of these medications, but more common during an overdose.

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.

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