Understanding Mydriasis
Mydriasis is the dilation of the pupil [1.2.4]. This physiological response can be triggered by low light or the body's sympathetic nervous system (the 'fight or flight' response) [1.2.4, 1.4.3]. However, it is most commonly induced pharmacologically for medical purposes, especially for ophthalmic examinations that require a clear view of the retina and other structures deep within the eye [1.2.4]. The size of the pupil is controlled by two opposing muscles in the iris: the iris sphincter, which constricts the pupil, and the iris dilator, which widens it [1.2.4]. Drugs that cause mydriasis, known as mydriatics, work by targeting the nerves that control these muscles [1.2.6].
Mechanisms of Pharmacological Mydriasis
There are two primary pharmacological pathways to induce mydriasis [1.2.1, 1.2.4]:
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Parasympathetic Blockade (Anticholinergic Action): The iris sphincter muscle is controlled by the parasympathetic nervous system, which uses acetylcholine as a neurotransmitter. Anticholinergic drugs block the muscarinic acetylcholine receptors on this muscle [1.3.5]. This prevents the muscle from constricting, allowing the opposing dilator muscle to widen the pupil unopposed [1.3.6]. This mechanism not only causes mydriasis but often also paralyzes the focusing muscles (cycloplegia) [1.2.5].
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Sympathetic Stimulation (Adrenergic Action): The iris dilator muscle is controlled by the sympathetic nervous system and has alpha-1 (α1) adrenergic receptors [1.2.1]. Sympathomimetic drugs mimic the action of norepinephrine, stimulating these α1-receptors [1.2.6]. This causes the dilator muscle to contract, actively pulling the pupil open [1.4.2]. This pathway typically produces mydriasis with less impact on accommodation (cycloplegia) compared to anticholinergics [1.4.8].
Key Drug Classes That Cause Mydriasis
Different classes of drugs, both for topical ophthalmic use and systemic administration, can result in pupil dilation.
Anticholinergics (Parasympatholytics)
These drugs are potent mydriatics and are widely used in ophthalmology. By blocking the parasympathetic stimulation to the iris sphincter muscle, they cause significant and often long-lasting dilation [1.3.3].
- Atropine: The most potent mydriatic and cycloplegic agent, with effects that can last for 7 to 14 days [1.3.6, 1.4.6]. Due to its long duration, it is typically used therapeutically (e.g., for managing uveitis) rather than for routine diagnostic exams [1.3.6].
- Tropicamide: A much shorter-acting anticholinergic, tropicamide is the most common drug used for routine dilated fundus examinations [1.6.2]. Its mydriatic effects begin within 15-30 minutes and last for about 4-8 hours [1.6.1].
- Scopolamine: Another strong anticholinergic agent, sometimes used for motion sickness, that can cause mydriasis lasting several days [1.3.7].
- Cyclopentolate: Commonly used for cycloplegic refractions in children, its effects last up to 24 hours [1.6.3, 1.6.5].
Sympathomimetics (Adrenergic Agonists)
These agents stimulate the iris dilator muscle directly. They are often used in combination with anticholinergics to achieve maximum dilation [1.6.7].
- Phenylephrine: A selective alpha-1 adrenergic receptor agonist that causes mydriasis by contracting the dilator muscle [1.2.6]. Its effects reach their maximum in 60-90 minutes and wear off after 5-7 hours [1.6.1]. It does not produce significant cycloplegia, making it useful when only dilation is needed [1.4.8].
- Epinephrine: A hormone and neurotransmitter that can be used topically to induce mydriasis through its action on adrenergic receptors [1.4.7].
Comparison of Common Ophthalmic Mydriatics
| Drug | Class | Onset of Action | Duration of Mydriasis | Primary Use |
|---|---|---|---|---|
| Atropine | Anticholinergic | Slow (approx. 1 hour) | 7-14 days [1.3.6] | Therapeutic (e.g., uveitis) [1.3.6] |
| Tropicamide | Anticholinergic | Fast (15-30 minutes) [1.6.1] | 4-8 hours [1.6.1] | Routine diagnostic exams [1.6.2] |
| Phenylephrine | Sympathomimetic | Moderate (60-90 minutes) [1.6.1] | 5-7 hours [1.6.1] | Diagnostic exams, often with tropicamide [1.6.7] |
Other Systemic and Recreational Drugs
A wide range of systemic medications and recreational substances can cause mydriasis as a side effect or intended effect, primarily through anticholinergic or sympathomimetic mechanisms [1.5.3, 1.5.5].
- Antidepressants: Tricyclic antidepressants (like amitriptyline) and some SSRIs can have anticholinergic effects that lead to mydriasis [1.3.3, 1.3.8].
- Stimulants: Drugs like amphetamines (including ADHD medications), cocaine, and MDMA (ecstasy) stimulate the sympathetic nervous system, causing pupil dilation [1.3.5, 1.4.4, 1.5.5]. Cocaine also blocks norepinephrine reuptake, prolonging this effect [1.4.1].
- Hallucinogens: Substances like LSD, psilocybin mushrooms, and mescaline often cause significant mydriasis [1.3.8, 1.5.2].
- Antihistamines: First-generation antihistamines (e.g., Benadryl) have anticholinergic properties and can cause pupil dilation [1.3.2].
- Other Medications: Drugs for Parkinson's disease, antiseizure medications, decongestants, and botulinum toxin (Botox) can also induce mydriasis [1.3.2, 1.3.5].
Conclusion
Mydriasis is pharmacologically achieved by either blocking the parasympathetic pathway with anticholinergics like atropine and tropicamide or stimulating the sympathetic pathway with sympathomimetics like phenylephrine [1.4.1]. While essential for ophthalmology, pupil dilation is also a notable side effect of many systemic medications and a common sign of recreational drug use, including stimulants and hallucinogens [1.5.8]. The choice of a mydriatic agent in a clinical setting depends on the required duration and whether cycloplegia is also needed.
Authoritative Link: Pharmacologic Dilation of Pupil - EyeWiki
