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 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 ...

, 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 Sjögren syndrome or Sjögren's syndrome (SjS, SS) is a Chronic disease, long-term autoimmune disease that affects the body's moisture-producing (lacrimal and salivary) glands, and often seriously affects other organ systems, such as the lungs, k ...

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. Radia ...

. 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 derma ...

and

retinal detachment Retinal detachment is a disorder of the eye in which the retina peels away from its underlying layer of support tissue. Initial detachment may be localized, but without rapid treatment the entire retina may detach, leading to vision loss and blin ...

. Use is generally not recommended during

pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ca ...

. Pilocarpine is in the

miotics Miosis, or myosis (), is excessive constriction of the pupil.Farlex medical dictionary
citing: ...

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 e ...

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 posterior ...

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 ...

. 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 Saliva (commonly referred to as spit) is an extracellular fluid produced and secreted by salivary glands in the mouth. In humans, saliva is around 99% water, plus electrolytes, mucus, white blood cells, epithelial cells (from which DNA can be ...

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 distribut ...

. It is used to prevent or treat

, particularly in

, 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 Adie syndrome, also known as Holmes-Adie syndrome, is a neurological disorder characterized by a tonically dilated pupil that reacts slowly to light but shows a more definite response to accommodation (i.e., light-near dissociation). It is fre ...

from other causes of unequal pupil size. It may be used to treat a form of

dry eye Dry or dryness most often refers to: * Lack of rainfall, which may refer to **Arid regions **Drought * Dry or dry area, relating to legal prohibition of selling, serving, or imbibing alcoholic beverages * Dry humor, deadpan * Dryness (medical) * ...

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 intraocu ...

. 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 Apraclonidine ( INN), also known under the brand name Iopidine, is a sympathomimetic used in glaucoma therapy. It is an α2 adrenergic receptor agonist and a weak α1 adrenergic receptor agonist. Topical apraclonidine is administered at a conc ...

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 s ...

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 The depth of field (DOF) is the distance between the nearest and the furthest objects that are in acceptably sharp focus in an image captured with a camera. Factors affecting depth of field For cameras that can only focus on one object dist ...

, similar to the effect of

pinhole glasses Pinhole glasses, also known as stenopeic glasses, are 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 only a very ...

. 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'', an ...

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 salts ...

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 iso ...

that is excreted in sweat. It is used to diagnose

cystic fibrosis Cystic fibrosis (CF) is a rare genetic disorder that affects mostly the lungs, but also the pancreas, liver, kidneys, and intestine. Long-term issues include difficulty breathing and coughing up mucus as a result of frequent lung infections. O ...

Adverse effects

Use of pilocarpine may result in a range of adverse effects, most of them related to its

non-selective In biochemistry and pharmacology, a ligand is a Chemical substance, substance that forms a Complex (chemistry), complex with a biomolecule to serve a biological purpose. The etymology stems from ''ligare'', which means 'to bind'. In protein-lig ...

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 is ...

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 Bradycardia (also sinus bradycardia) is a slow resting heart rate, commonly under 60 beats per minute (BPM) as determined by an electrocardiogram. It is considered to be a normal heart rate during sleep, in young and healthy or elderly adults, a ...

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 vasoconstriction, ...

, 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 wi ...

. 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 Miosis, or myosis (), is excessive constriction of the pupil.Farlex medical dictionary
citing: ...

. 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 The iris sphincter muscle (pupillary sphincter, pupillary constrictor, circular muscle of iris, circular fibers) is a muscle in the part of the eye called the iris. It encircles the pupil of the iris, appropriate to its function as a constrictor ...

, causing the muscle to contract - resulting in pupil constriction (

miosis Miosis, or myosis (), is excessive constriction of the pupil.Farlex medical dictionary
citing: ...

). 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 The scleral spur in the visual system is a protrusion of the sclera (the white of the eye) into the anterior chamber. The spur is an annular structure composed of collagen in the human eye. It is the origin of the longitudinal and circular fib ...

. 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 to ...

. 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 The anterior chamber angle is a part of the eye located between the cornea and Iris (anatomy), iris which contains the trabecular meshwork. The size of this angle is an important determinant of the rate aqueous humour flows out of the eye, and thu ...

. 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 (chemistry), alcohol with the chemical formula . Its formula can be also written as or (an ethyl ...

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 was ...

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 Chloroform, or trichloromethane, is an organic compound with chemical formula, formula Carbon, CHydrogen, HChlorine, Cl3 and a common organic solvent. It is a colorless, strong-smelling, dense liquid produced on a large scale as a precursor to ...

. 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 electrical ...

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 na ...

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

, 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, gastroenteri ...

xylazine Xylazine is a pharmaceutical drug used for sedation, anesthesia, muscle relaxation, and analgesia in animals such as horses, cattle, and other non-human mammals. Veterinarians also use xylazine as an emetic, especially in cats. It is an anal ...

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