What medications cause miosis?

Pinpoint pupils, medically known as miosis, are a classic sign of an opioid overdose, but this is not the only cause [1.2.8]. Numerous prescription and non-prescription drugs can lead to this condition. So, what medications cause miosis?

Quick Summary

A detailed overview of the various classes of drugs known to cause pupillary constriction, or miosis. It covers the mechanisms of action for opioids, cholinergics, antipsychotics, and others, while detailing the clinical significance.

Key Points

• Opioids are a Primary Cause: Drugs like morphine, fentanyl, and heroin are well-known for causing pinpoint pupils by stimulating the central nervous system's parasympathetic pathways [1.3.3, 1.3.2].

• Cholinergic Drugs Act Directly: Medications like pilocarpine eye drops (for glaucoma) and toxins like organophosphates cause miosis by directly acting on the iris muscles [1.4.2, 1.5.5].

• Antipsychotics and Sedatives are Implicated: Certain antipsychotics (e.g., olanzapine, haloperidol) and sedatives like benzodiazepines can also lead to constricted pupils [1.5.2, 1.2.7].

• Other Medications Can Be Responsible: Some blood pressure medications (like clonidine) and antidepressants (like mirtazapine) are also known to cause miosis as a side effect [1.2.3, 1.2.4].

• Mechanism Varies by Drug Class: The reason for miosis differs; opioids act on the brainstem, while cholinergics act directly on the eye's muscles [1.3.2, 1.4.2].

• Clinical Importance: Drug-induced miosis is a key diagnostic sign, especially for identifying opioid overdose, which can be accompanied by life-threatening respiratory depression [1.2.8, 1.7.7].

• Not Always a Sign of Overdose: While prominent in overdoses, miosis can also be a standard side effect of therapeutic doses of certain medications, such as glaucoma eye drops [1.4.6].

Understanding Miosis: The Science of Pinpoint Pupils

Miosis is the medical term for the constriction, or shrinking, of the pupil [1.2.7]. The size of the pupil is controlled by two opposing muscles in the iris: the sphincter pupillae, which constricts the pupil, and the dilator pupillae, which enlarges it [1.6.4]. This process is regulated by the autonomic nervous system. The parasympathetic nervous system triggers constriction (miosis), while the sympathetic nervous system causes dilation (mydriasis) [1.6.4, 1.6.1].

While changes in light naturally cause the pupil to adjust, certain medications can disrupt this balance, leading to persistent and often significant pupillary constriction. Drug-induced miosis occurs when a substance either stimulates the parasympathetic pathway or inhibits the sympathetic pathway that controls the eye [1.3.5, 1.5.5]. This effect is a key diagnostic clue in many clinical situations, especially in toxicology and emergency medicine.

Primary Culprits: Opioids and Cholinergics

Two classes of drugs are most famously associated with causing miosis: opioids and cholinergic agents.

Opioids and Their Effect on the Eyes

Opioids are a class of powerful pain-relieving drugs that include prescription medications like morphine, oxycodone, fentanyl, and hydrocodone, as well as illicit drugs like heroin [1.2.2, 1.2.5]. One of the hallmark signs of opioid use, and particularly overdose, is the presentation of "pinpoint pupils" [1.2.8].

Mechanism of Action: Opioids induce miosis by stimulating the Edinger-Westphal nucleus in the brainstem [1.3.2]. This action increases the parasympathetic nervous system's output to the eye, causing the circular iris sphincter muscle to contract and the pupil to shrink significantly [1.3.5, 1.3.2]. This response is so characteristic that it is used by medical professionals to help diagnose opioid toxicity [1.3.5]. The effect is not mediated by local receptors in the eye but through the central nervous system.

Common opioids that cause miosis include:

• Morphine [1.2.4]
• Heroin [1.2.4]
• Fentanyl [1.2.5]
• Oxycodone (OxyContin, Percocet) [1.3.3]
• Hydrocodone (Vicodin) [1.3.3]
• Codeine [1.2.2]
• Methadone [1.2.4]

Cholinergic Agents

Cholinergic drugs work by mimicking or enhancing the action of the neurotransmitter acetylcholine. Since acetylcholine is the primary neurotransmitter of the parasympathetic nervous system, these drugs directly stimulate the iris sphincter muscle to contract, resulting in miosis [1.4.2, 1.6.5].

This class includes:

• Direct-acting miotics: These are often administered as eye drops to treat conditions like glaucoma. Pilocarpine and Carbachol are common examples [1.4.7, 1.4.2]. Pilocarpine works by directly stimulating muscarinic receptors on the iris sphincter, causing pupillary constriction and increasing the outflow of aqueous humor to reduce intraocular pressure [1.4.6, 1.4.2].
• Cholinesterase inhibitors: These drugs work by preventing the breakdown of acetylcholine, thereby increasing its availability and effect. This can happen through medications used for conditions like myasthenia gravis or Alzheimer's disease (e.g., neostigmine, donepezil) or through exposure to toxins like organophosphate pesticides and nerve agents [1.5.5, 1.2.4].

Other Medications That Can Cause Miosis

Beyond opioids and cholinergics, a variety of other prescription and over-the-counter medications can lead to pupil constriction.

Antipsychotics and Sedatives

Certain antipsychotic medications, particularly older (first-generation) and some newer (atypical) ones, are associated with miosis. This is often due to their effect on various neurotransmitter systems, including the blockade of alpha-1 adrenergic receptors, which can lead to unopposed parasympathetic stimulation [1.5.6, 1.5.5].

Examples include:

• Haloperidol (Haldol) [1.2.3]
• Chlorpromazine [1.5.2]
• Olanzapine (Zyprexa) [1.5.2, 1.5.4]
• Quetiapine (Seroquel) [1.5.2]
• Risperidone [1.5.2]

Sedatives like benzodiazepines and barbiturates can also cause miosis, although this is more commonly seen in overdose situations [1.2.7, 1.4.8].

Blood Pressure Medications and Other Drugs

Some medications used to treat high blood pressure can cause miosis as a side effect. Clonidine is a frequently cited example [1.2.3, 1.2.1]. Certain antidepressants, such as mirtazapine, have also been linked to miosis, especially in cases of overdose [1.2.3, 1.2.4]. Nicotine, through its influence on the nervous system, can also cause miotic pupils over time with chronic use [1.2.1, 1.2.4].

Comparison of Major Drug Classes Causing Miosis

Drug Class	Mechanism of Action	Common Examples	Clinical Context
Opioids	Central nervous system stimulation of the parasympathetic pathway via the Edinger-Westphal nucleus [1.3.2].	Morphine, Fentanyl, Oxycodone, Heroin [1.2.4, 1.2.5].	Pain management, substance use, classic sign of overdose [1.3.5].
Cholinergics	Direct stimulation of muscarinic receptors on the iris sphincter muscle or inhibition of acetylcholinesterase [1.4.2, 1.5.5].	Pilocarpine, Carbachol (eye drops), Organophosphates [1.4.7, 1.4.2].	Glaucoma treatment, poisoning/toxic exposure [1.4.6, 1.2.6].
Antipsychotics	Blockade of α1-adrenergic receptors, leading to unopposed parasympathetic action [1.5.6, 1.5.5].	Haloperidol, Olanzapine, Risperidone [1.2.3, 1.5.2].	Treatment of psychiatric disorders; side effect may be more pronounced in overdose [1.5.4].
Antihypertensives	Varies by drug; Clonidine acts centrally to reduce sympathetic outflow [1.6.6].	Clonidine [1.2.3].	Treatment of high blood pressure [1.2.5].

Clinical Significance and Conclusion

Drug-induced miosis is more than just an interesting pharmacological side effect; it's a critical diagnostic sign. In an emergency setting, pinpoint pupils that are unresponsive to light are a strong indicator of opioid overdose and can prompt the life-saving administration of naloxone [1.2.8, 1.4.4]. While the pupil constriction itself is not typically harmful, it can cause blurred vision and difficulty seeing in dim light [1.4.2]. More importantly, it often signals the presence of a drug's systemic effects, which could include dangerous respiratory depression in the case of opioids [1.7.7].

If you notice sudden, unexplained pupil constriction in yourself or someone else, especially when accompanied by other symptoms like drowsiness, confusion, or slowed breathing, it is crucial to seek immediate medical attention. Understanding what medications cause miosis helps both patients and clinicians identify potential adverse drug reactions and critical health emergencies.

---

For further reading, the National Library of Medicine's resource on pupillary effects of opioids provides in-depth information on the topic: https://pubmed.ncbi.nlm.nih.gov/25068603/

Frequently Asked Questions

What is the most common cause of drug-induced miosis?

Opioids are the most well-known and clinically significant cause of drug-induced miosis, or pinpoint pupils. This includes prescription painkillers like oxycodone and fentanyl, as well as illicit drugs like heroin [1.3.3, 1.2.5].

Do all opioids cause pinpoint pupils?

Most opioids, such as morphine, heroin, and fentanyl, cause miosis. However, there can be exceptions. For example, pethidine (meperidine) is noted as an opioid that does not typically cause miosis [1.2.4].

Can eye drops cause miosis?

Yes, certain eye drops, known as miotics, are designed to constrict the pupil. Pilocarpine and carbachol are common examples used to treat glaucoma by increasing fluid drainage from the eye [1.4.2, 1.4.7].

Is drug-induced miosis dangerous?

The miosis itself is not typically dangerous, though it can cause blurry vision. The danger lies in what it signifies. In the case of opioids, pinpoint pupils can be a sign of an overdose, which often involves life-threatening respiratory depression [1.7.7].

Which antipsychotic medications can cause pupil constriction?

Several antipsychotics have been associated with miosis, including risperidone, haloperidol, chlorpromazine, olanzapine, and quetiapine [1.5.2, 1.2.3].

How do opioids cause miosis?

Opioids cause miosis by stimulating the parasympathetic nervous system through the Edinger-Westphal nucleus in the brainstem. This sends a signal to the iris sphincter muscle to contract, making the pupil smaller [1.3.2, 1.3.5].

Can blood pressure medication cause pinpoint pupils?

Yes, some medications for high blood pressure can cause miosis. Clonidine is a frequently cited example of an antihypertensive drug that has pupillary constriction as a potential side effect [1.2.3, 1.2.5].