Mydriasis

Mydriasis is a dilation of the pupil due to disease, trauma or the use of drugs. Normally, the pupil dilates in the dark and constricts in the light to respectively improve vividity at night and to protect the retina from sunlight damage during the day. A mydriatic pupil will remain excessively large even in a bright environment and is sometimes colloquially referred to as a "blown pupil". More generally, mydriasis refers to the dilation of pupils, for instance in low light conditions or under sympathetic stimulation. The excitation of the radial fibres of the iris which increases the pupillary aperature is referred to as a mydriasis.

The opposite, constriction of the pupil, is referred to as miosis. Both mydriasis and miosis can be physiological.

Mechanism
There are two types of muscle that control the size of the iris: circular muscle and radial muscle. The former is innervated by the parasympathetic nervous system, the latter by the sympathetic nervous system. Sympathetic stimulation of α1 adrenergic receptors causes the contraction of the radial muscle, and subsequent dilation of the pupil. Conversely, parasympathetic stimulation cause contraction of the circular muscle and constriction of the pupil.

The mechanism of mydriasis depends on the agent being used. It usually involves either a disruption of the parasympathetic nerve supply to the eye (which causes contraction of the pupil), or overactivity of the sympathetic nervous system (SNS).

Effects
Natural release of the hormone oxytocin can cause mild to moderate mydriasis. Strong sexual arousal can often lead to very enlarged pupils, rather than the minor dilation observed during sexual affection. Orgasm has been reported to lead to pupillary block in a single case in combination with an ocular precondition. Here the parasympathetic and sympathetic stimulation lead to sphincter muscle stimulation during pupillary dilation in the dark, while ciliary contraction caused zonular relaxation leading to pupillary block and angle-closure in combination with pre-existing narrow chamber angle.

Autonomic neuropathy
The parasympathetic nervous supply, which causes constriction of the pupil, or miosis, is supplied by cranial nerve III, the oculomotor nerve. Damage to this nerve typically manifests itself as mydriasis, because the sympathetic supply to the pupil, which causes mydriasis, remains unaffected, and therefore unopposed. Multiple central nervous system disorders e.g. epilepsy, stroke are known to lead to temporal mydriasis as well.

Traumatic
In cases of head injury or orbit trauma (eye injury), the iris sphincter (the muscle responsible for closing the pupil) or the nerves controlling it can be damaged, reducing or eliminating consensual reactivity to light.

Drugs
Anticholinergics such as atropine, hyoscyamine, and scopolamine antagonize the muscarinic acetylcholine receptors in the eye. By blocking these receptors, the pupils are no longer capable of constriction and dilation results. Such alkaloids present in many plants of the family Solanaceae may also induce mydriasis when used recreationally.

Most hallucinogens such as LSD, psilocybin, and mescaline, in addition to some other phenethylamines and tryptamines, all produce mydriasis by agonizing the serotonergic 5-HT2A receptors in the brain. Dissociatives such as ketamine, DXM, and PCP do so as well via antagonism of the NMDA glutamate receptors. There have also been reports that the atypical psychedelic herb salvia divinorum causes mydriasis. It works via agonism of the κ-Opioid receptors in the brain. How the neurological changes induced by these drugs ultimately causes pupil dilation is unknown.

Drugs that increase overall serotonin levels in general are capable of causing mydriasis in the same way as the 5-HT2A-mediated psychedelics. This is because serotonin itself is naturally responsible for normal 5-HT2A stimulation. Hence, in sufficient quantities serotonin is mydriatic and can even be mildly psychedelic, though the potentially fatal serotonin syndrome usually ensues before the psychedelia becomes overly-pronounced. Examples of such drugs include MDMA (as well as other MDxx compounds), fenfluramine, chlorphentermine, stimulants (including cocaine and amphetamines), and some antidepressants (such as SSRIs, SNRIs, and MAOIs). Natural serotonin-boosting supplements such as L-Tryptophan and 5-HTP are also capable of this, but usually only in excessive doses.

The neurotransmitter norepinephrine regulates many physiological processes in the body and brain. One of them is the autonomic constriction and contraction of certain muscles. The psychoactive drug cocaine potently inhibits the normal reuptake of norepinephrine into presynaptic nerve terminals resulting in an increased level of extracellular norepinephrine. Amphetamines also potently release and prevent the reuptake of norepinephrine. The released norepinephrine then proceeds to bind to adrenergic receptors, and the biological effects of norepinephrine finally occur. When a solution of cocaine is dropped into the eye, this process takes place, and the end result is dilation of the pupil. Cocaine itself is not typically used for this task however. Any potent norepinephrine reuptake inhibitor or release agent should be capable of such an effect.

Opioids such as morphine and heroin cause miosis. Subsequently, mydriasis occasionally occurs during opioid rebound and withdrawal.

Mydriatics
A mydriatic is an agent that induces dilation of the pupil. Drugs such as tropicamide are used in medicine to permit examination of the retina and other deep structures of the eye, and also to reduce painful ciliary muscle spasm (see cycloplegia). Phenylephrine (e.g. Cyclomydril ) is used if strong mydriasis is needed for a surgical intervention. One effect of administration of a mydriatic is intolerance to bright light (Photophobia). Purposely-induced mydriasis via mydriatics is also used as a diagnostic test for Horner's Syndrome.