The Autonomic Nervous System and Pupil Control
Before diving into which drugs cause mydriasis, it is essential to understand the basic physiology of pupil control. The size of the pupil is regulated by two opposing sets of muscles within the iris, which are in turn controlled by the autonomic nervous system.
- The Sympathetic Nervous System: Often called the “fight or flight” system, it is responsible for pupil dilation (mydriasis). It stimulates the iris dilator muscles to contract, increasing the pupil's size to let in more light.
- The Parasympathetic Nervous System: Referred to as the “rest and digest” system, it controls pupil constriction (miosis). It activates the iris sphincter muscles to contract, making the pupil smaller.
Drugs that cause mydriasis achieve this effect by either stimulating the sympathetic system or blocking the parasympathetic system.
Anticholinergic Agents
Anticholinergics are a major class of drugs that cause mydriasis by blocking the parasympathetic nervous system. Specifically, they block the action of acetylcholine, a neurotransmitter that tells the iris sphincter muscle to constrict. Without this signal, the pupil dilates.
Examples of anticholinergic drugs:
Anticholinergic drugs that can cause mydriasis include atropine and scopolamine, which are used medically for various purposes. Ophthalmic drops like tropicamide and cyclopentolate are also anticholinergics used for eye exams. Additionally, certain older medications such as first-generation antihistamines (e.g., diphenhydramine) and tricyclic antidepressants (e.g., amitriptyline) have anticholinergic properties that can lead to pupil dilation.
Sympathomimetic Agents
Sympathomimetic drugs mimic the effects of the sympathetic nervous system, directly stimulating the iris dilator muscle and causing the pupils to enlarge.
Examples of sympathomimetic drugs:
Stimulant drugs such as cocaine, amphetamines (including methamphetamine and Adderall), and MDMA (Ecstasy) are well-known sympathomimetics that cause mydriasis by increasing levels of norepinephrine. Phenylephrine, an alpha-adrenergic agonist, is used in ophthalmic drops for dilation and can also be found in some oral decongestants.
Hallucinogens
Hallucinogenic substances often cause significant and prolonged pupil dilation through their effects on various neurotransmitter systems, including serotonin.
Examples of hallucinogens:
Common hallucinogens that cause mydriasis include LSD, psilocybin (found in mushrooms), and mescaline. The dilation caused by these substances can be marked and last for many hours.
A Comparison of Mydriatic Drug Classes
| Drug Class | Mechanism | Onset of Effect | Duration of Effect | Common Examples |
|---|---|---|---|---|
| Anticholinergics | Blocks acetylcholine, preventing constriction | Slower (minutes to hours) | Varies, can be long (hours to days) | Atropine, Scopolamine, Tropicamide |
| Sympathomimetics | Stimulates norepinephrine, causing dilation | Rapid (minutes) | Hours to several hours | Cocaine, Amphetamines, Phenylephrine |
| Hallucinogens | Affects serotonin and other neurotransmitters | Slower (minutes to hours) | Prolonged (hours to >12 hours) | LSD, Psilocybin, MDMA |
| Antidepressants (TCAs) | Blocks acetylcholine and other receptors | Gradual (weeks to reach full effect) | Varies based on metabolism | Amitriptyline, Imipramine |
Other Medications and Factors
Beyond the primary drug classes, other substances can also cause pupil dilation. Some oral decongestants that contain sympathomimetic ingredients like pseudoephedrine can cause mild mydriasis. High doses of caffeine have also been cited as a potential cause.
Botulinum toxin (Botox), when it is absorbed systemically, can cause bilateral dilated pupils. Additionally, it is important to note that opioids do not cause mydriasis; rather, they typically cause miosis (constricted pupils), which can become dilated in cases of oxygen deprivation during an overdose.
When to Seek Medical Attention
While therapeutically induced mydriasis for an eye exam is a controlled and temporary event, drug-induced dilation from recreational use or medication side effects can have significant consequences. These include increased light sensitivity (photophobia), blurred vision, and difficulty focusing.
Furthermore, mydriasis combined with other symptoms like altered mental status, agitation, or severe heart palpitations can be a sign of a drug overdose or a dangerous drug interaction. A fixed, unilateral dilated pupil can be a sign of a life-threatening neurological emergency, such as a cranial nerve injury or increased intracranial pressure. It is crucial to seek immediate medical help in such cases.
Conclusion
Numerous drugs can cause mydriasis by affecting the delicate balance of the autonomic nervous system. Anticholinergics like atropine inhibit the pupil's constricting function, while sympathomimetics like cocaine activate its dilating function. Hallucinogens also cause dilation through their complex effects on neurotransmitters. Understanding which drug causes mydriasis and its mechanism is vital for healthcare professionals to make an accurate diagnosis and for the public to recognize the potential risks associated with both recreational drug use and certain prescription medications.
For more information on the pupillary light reflex and drug effects, consult the EyeWiki entry on Pharmacologic Dilation of Pupil.
