Pilocarpine is a medication used to reduce pressure inside the eye and treat

dry mouth Xerostomia, also known as dry mouth, is dryness in the mouth, which may be associated with a change in the composition of saliva, or reduced salivary flow, or have no identifiable cause. This symptom is very common and is often seen as a side eff ...

. As

eye drops Eye drops or eyedrops are liquid drops applied directly to the surface of the eye usually in small amounts such as a single drop or a few drops. Eye drops usually contain saline to match the salinity of the eye. Drops containing only saline ...

it is used to manage

angle closure glaucoma Glaucoma is a group of eye diseases that result in damage to the optic nerve (or retina) and cause vision loss. The most common type is open-angle (wide angle, chronic simple) glaucoma, in which the drainage angle for fluid within the eye rem ...

until surgery can be performed,

ocular hypertension Ocular hypertension is the presence of elevated fluid pressure inside the eye (intraocular pressure), usually with no optic nerve damage or visual field loss. For most individuals, the normal range of intraocular pressure is between 10 mmHg and 2 ...

, primary open angle glaucoma, and to bring about constriction of the pupil following its dilation. However, due to its side effects it is no longer typically used in the long term management. Onset of effects with the drops is typically within an hour and lasts for up to a day. By mouth it is used for dry mouth as a result of Sjögren syndrome or

radiation therapy Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Radi ...

. Common side effects of the eye drops include irritation of the eye, increased tearing, headache, and blurry vision. Other side effects include

allergic reactions Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic derm ...

and retinal detachment. Use is generally not recommended during

pregnancy Pregnancy is the time during which one or more offspring develops (gestation, gestates) inside a woman, woman's uterus (womb). A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occur ...

. Pilocarpine is in the miotics family of medication. It works by activating

cholinergic receptors An acetylcholine receptor (abbreviated AChR) is an integral membrane protein that responds to the binding of acetylcholine, a neurotransmitter. Classification Like other transmembrane receptors, acetylcholine receptors are classified according ...

of the muscarinic type which cause the

trabecular meshwork The trabecular meshwork is an area of tissue in the eye located around the base of the cornea, near the ciliary body, and is responsible for draining the aqueous humor from the eye via the anterior chamber (the chamber on the front of the ...

to open and the

aqueous humor The aqueous humour is a transparent water-like fluid similar to plasma, but containing low protein concentrations. It is secreted from the ciliary body, a structure supporting the lens of the eyeball. It fills both the anterior and the posteri ...

to drain from the eye. Pilocarpine was isolated in 1874 by Hardy and Gerrard and has been used to treat glaucoma for more than 100 years. It is on the

World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...

. It was originally made from the South American plant ''

Pilocarpus ''Pilocarpus'' is a genus of about 13 species of plants belonging to the family Rutaceae, native to the Neotropics of South America. Various species are important pharmacologically as a source of the parasympathomimetic alkaloid pilocarpine ...

''.

Medical uses

Pilocarpine stimulates the secretion of large amounts of saliva and

sweat Perspiration, also known as sweating, is the production of fluids secreted by the sweat glands in the skin of mammals. Two types of sweat glands can be found in humans: eccrine glands and apocrine glands. The eccrine sweat glands are distrib ...

. It is used to prevent or treat

, particularly in Sjögren syndrome, but also as a side effect of

for

head and neck cancer Head and neck cancer develops from tissues in the lip and oral cavity (mouth), larynx (throat), salivary glands, nose, sinuses or the skin of the face. The most common types of head and neck cancers occur in the lip, mouth, and larynx. Symptoms ...

. It may be used to help differentiate Adie syndrome from other causes of unequal pupil size. It may be used to treat a form of dry eye called ''aqueous deficient dry eye (ADDE)''

Surgery

Pilocarpine is sometimes used immediately before certain types of corneal grafts and

cataract surgery Cataract surgery, also called lens replacement surgery, is the removal of the natural lens of the eye (also called "crystalline lens") that has developed an opacification, which is referred to as a cataract, and its replacement with an intra ...

. It is also used prior to YAG laser iridotomy. In ophthalmology, pilocarpine is also used to reduce symptomatic glare at night from lights when the patient has undergone implantation of

phakic intraocular lens A phakic intraocular lens (PIOL) is a special kind of intraocular lens that is implanted surgically into the eye to correct myopia (nearsightedness). It is called "phakic" (meaning "having a lens") because the eye's natural lens is left untouched. ...

es; the use of pilocarpine would reduce the size of the pupils, partially relieving these symptoms. The most common concentration for this use is pilocarpine 1%. Pilocarpine is shown to be just as effective as apraclonidine in preventing intraocular pressure spikes after laser trabeculoplasty.

Presbyopia

In 2021, the

US Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

approved pilocarpine hydrochloride as an eyedrop treatment for

presbyopia Presbyopia is physiological insufficiency of accommodation associated with the aging of the eye that results in progressively worsening ability to focus clearly on close objects. Also known as age-related farsightedness (or age-related long si ...

, age-related difficulty with near-in vision. It works by causing the pupils to constrict, increasing depth of field, similar to the effect of

pinhole glasses Pinhole glasses, also known as stenopeic glasses, are glasses, eyeglasses with a series of pinhole-sized perforations filling an opaque sheet of plastic in place of each lens. Similar to the workings of a pinhole camera, each perforation allows on ...

. Marketed as Vuity, the effect lasts for more than 6 hours.

Other

Pilocarpine is used to stimulate sweat glands in a sweat test to measure the

concentration In chemistry, concentration is the abundance of a constituent divided by the total volume of a mixture. Several types of mathematical description can be distinguished: '' mass concentration'', ''molar concentration'', '' number concentration'', ...

chloride The chloride ion is the anion (negatively charged ion) Cl−. It is formed when the element chlorine (a halogen) gains an electron or when a compound such as hydrogen chloride is dissolved in water or other polar solvents. Chloride sa ...

and

sodium Sodium is a chemical element with the symbol Na (from Latin ''natrium'') and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 of the periodic table. Its only stable ...

that is excreted in sweat. It is used to diagnose cystic fibrosis.

Adverse effects

Use of pilocarpine may result in a range of adverse effects, most of them related to its non-selective action as a muscarinic receptor agonist. Pilocarpine has been known to cause excessive salivation, sweating, bronchial

mucus Mucus ( ) is a slippery aqueous secretion produced by, and covering, mucous membranes. It is typically produced from cells found in mucous glands, although it may also originate from mixed glands, which contain both serous and mucous cells. It ...

secretion,

bronchospasm Bronchospasm or a bronchial spasm is a sudden constriction of the muscles in the walls of the bronchioles. It is caused by the release (degranulation) of substances from mast cells or basophils under the influence of anaphylatoxins. It causes di ...

, bradycardia,

vasodilation Vasodilation is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. The process is the opposite of vasoconstrictio ...

, and

diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin w ...

. Eye drops can result in brow

ache Ache or Aches may refer to: Ethnography * Aché, an indigenous people of eastern Paraguay * Aché language, the language of the Aché people * Ache language (China) * Aṣẹ (Cuban spelling: ''aché''), a concept in Orisha belief People * Ach ...

and chronic use in miosis. It can also cause temporary blurred vision or darkness of vision, temporary shortsightedness,

hyphema Hyphema is a condition that occurs when blood enters the front (anterior) chamber of the eye between the iris and the cornea. People usually first notice a loss of vision or decrease in vision. The eye may also appear to have a reddish tinge, o ...

and retinal detachment.

Pharmacology

Pilocarpine is a drug that acts as a muscarinic receptor agonist. It acts on a subtype of muscarinic receptor ( M₃) found on the iris sphincter muscle, causing the muscle to contract - resulting in pupil constriction ( miosis). Pilocarpine also acts on the

ciliary muscle The ciliary muscle is an intrinsic muscle of the eye formed as a ring of smooth muscleSchachar, Ronald A. (2012). "Anatomy and Physiology." (Chapter 4) . in the eye's middle layer, uvea (vascular layer). It controls accommodation for viewing ...

and causes it to contract. When the ciliary muscle contracts, it opens the

through increased tension on the scleral spur. This action facilitates the rate that

leaves the eye to decrease

intraocular pressure Intraocular pressure (IOP) is the fluid pressure inside the eye. Tonometry is the method eye care professionals use to determine this. IOP is an important aspect in the evaluation of patients at risk of glaucoma. Most tonometers are calibrated t ...

. Paradoxically, when pilocarpine induces this ciliary muscle contraction (known as an

accommodative spasm A spasm of accommodation (also known as a ciliary spasm, an accommodation, or accommodative spasm) is a condition in which the ciliary muscle of the eye remains in a constant state of contraction. Normal accommodation allows the eye to "accommoda ...

) it causes the eye's

lens A lens is a transmissive optical device which focuses or disperses a light beam by means of refraction. A simple lens consists of a single piece of transparent material, while a compound lens consists of several simple lenses (''elements ...

to thicken and move forward within the eye. This movement causes the iris (which is located immediately in front of the lens) to also move forward, narrowing the Anterior chamber angle. Narrowing of the anterior chamber angle increases the risk of increased

Society and culture

Preparation

Plants in the genus ''

'' are the only known sources of pilocarpine, and commercial production is derived entirely from the leaves of '' Pilocarpus microphyllus'' (Maranham Jaborandi). This genus grows only in South America, and ''Pilocarpus microphyllus'' is native to several states in northern Brazil. Pilocarpine is extracted from the powdered leaf material in a multi-step process. First the material is treated with

ethanol Ethanol (abbr. EtOH; also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound. It is an alcohol with the chemical formula . Its formula can be also written as or (an ethyl group linked to a ...

acidified with

hydrochloric acid Hydrochloric acid, also known as muriatic acid, is an aqueous solution of hydrogen chloride. It is a colorless solution with a distinctive pungent smell. It is classified as a strong acid Acid strength is the tendency of an acid, symbol ...

, and the solvents removed under reduced pressure. The resultant aqueous residue is neutralized with

ammonia Ammonia is an inorganic compound of nitrogen and hydrogen with the formula . A stable binary hydride, and the simplest pnictogen hydride, ammonia is a colourless gas with a distinct pungent smell. Biologically, it is a common nitrogenous wa ...

and put aside until the resin has completely settled. It is then filtered and concentrated by sugar solution to a small volume, made alkaline with ammonia, and finally extracted with chloroform. The solvent is removed under reduced pressure.

Trade names

Pilocarpine is available under several trade names such as: Diocarpine (Dioptic), Isopto Carpine ( Alcon), Miocarpine (CIBA Vision), Ocusert Pilo-20 and -40 (Alza), Pilopine HS (Alcon), Salagen (MGI Pharma), Scheinpharm Pilocarpine (Schein Pharmaceutical), Timpilo (Merck Frosst), and Vuity (AbbVie).

Research

Pilocarpine is used to induce chronic

epilepsy Epilepsy is a group of non-communicable neurological disorders characterized by recurrent epileptic seizures. Epileptic seizures can vary from brief and nearly undetectable periods to long periods of vigorous shaking due to abnormal electrica ...

rodent Rodents (from Latin , 'to gnaw') are mammals of the order Rodentia (), which are characterized by a single pair of continuously growing incisors in each of the upper and lower jaws. About 40% of all mammal species are rodents. They are n ...

s, commonly rats, as a means to study the disorder's physiology and to examine different treatments. Smaller doses may be used to induce salivation in order to collect samples of saliva, for instance, to obtain information about IgA antibodies.

Veterinary

Pilocarpine is given in moderate doses (about 2 mg) to induce emesis in cats that have ingested foreign plants, foods, or drugs. One feline trial determined it was effective, even though the usual choice of

emetic Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenteritis ...

is xylazine.

References

External links

* {{Portal bar, Medicine Ophthalmology drugs Imidazoles Tetrahydrofurans Novartis brands Pfizer brands Gamma-lactones Muscarinic agonists Alkaloids found in Rutaceae World Health Organization essential medicines Wikipedia medicine articles ready to translate