Pilocarpine#Presbyopia
{{Short description|Medication used to treat glaucoma and dry mouth}}
{{Use dmy dates|date=January 2025}}
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{{Infobox drug
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| verifiedrevid = 464206617
| image = Pilocarpine.svg
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| width = 180
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| image2 = Pilocarpine ball-and-stick model.png
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| tradename = Pilopine HS, others
| Drugs.com = {{drugs.com|monograph|pilocarpine}}
| MedlinePlus = a608039
| DailyMedID = Pilocarpine
| pregnancy_AU = B3
| pregnancy_AU_comment =
| pregnancy_category =
| routes_of_administration = Topical eye drops, by mouth
| class = {{plainlist|
| ATC_prefix = N07
| ATC_suffix = AX01
| ATC_supplemental = {{ATC|S01|EB01}}
| legal_AU = S4
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| legal_UK = POM
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| legal_US = Rx-only
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| elimination_half-life = 0.76 hours (5 mg), 1.35 hours (10 mg){{cite journal | vauthors = Gornitsky M, Shenouda G, Sultanem K, Katz H, Hier M, Black M, Velly AM | title = Double-blind randomized, placebo-controlled study of pilocarpine to salvage salivary gland function during radiotherapy of patients with head and neck cancer | journal = Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics | volume = 98 | issue = 1 | pages = 45–52 | date = July 2004 | pmid = 15243470 | doi = 10.1016/j.tripleo.2004.04.009 }}
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| excretion = urine
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 92-13-7
| CAS_number2 = 54-71-7
| PubChem = 5910
| IUPHAR_ligand = 305
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB01085
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 5699
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 01MI4Q9DI3
| UNII2 = 0WW6D218XJ
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00525
| KEGG2 = D02200
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 8207
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 550
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| IUPAC_name = (3S,4R)-3-Ethyl-4-((1-methyl-1H-imidazol-5-yl)methyl)dihydrofuran-2(3H)-one
| C = 11
| H = 16
| N = 2
| O = 2
| SMILES = O=C2OC[C@H](Cc1n(cnc1)C)[C@@H]2CC
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C11H16N2O2/c1-3-10-8(6-15-11(10)14)4-9-5-12-7-13(9)2/h5,7-8,10H,3-4,6H2,1-2H3/t8-,10-/m0/s1
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| StdInChIKey = QCHFTSOMWOSFHM-WPRPVWTQSA-N
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Pilocarpine, sold under the brand name Pilopine HS among others, is a lactone alkaloid originally extracted from plants of the Pilocarpus genus.{{cite book |doi=10.1016/B978-044452166-8/50013-3 |chapter=Cholinomimetics |title=Synthesis of Essential Drugs |date=2006 | vauthors = Vardanyan RS, Hruby VJ |pages=179–193 |isbn=978-0-444-52166-8 }} It is used as a medication to reduce pressure inside the eye and treat dry mouth.{{cite book |title=Tarascon Pocket Pharmacopoeia 2019 Deluxe Lab-Coat Edition |date=2018 |publisher=Jones & Bartlett Learning |isbn=978-1-284-16754-2 |page=224 |url=https://books.google.com/books?id=pYZ-DwAAQBAJ&pg=PP224 }} As an eye drop it is used to manage angle closure glaucoma until surgery can be performed, ocular hypertension, primary open angle glaucoma, and to constrict the pupil after dilation.{{cite book | title = WHO Model Formulary 2008 | year = 2009 | isbn = 9789241547659 | vauthors = ((World Health Organization)) | veditors = Stuart MC, Kouimtzi M, Hill SR | hdl = 10665/44053 | author-link = World Health Organization | publisher = World Health Organization | hdl-access=free | page=439 }}{{cite web |title=Glaucoma and ocular hypertension. NICE guideline 81 |url=https://bnf.nice.org.uk/treatment-summary/glaucoma-and-ocular-hypertension.html |publisher=National Institute for Health and Care Excellence. |access-date=19 September 2019 |date=November 2017 |quote=Ocular hypertension... alternative options include carbonic anhydrase inhibitors such as brinzolamide or dorzolamide, a topical sympathomimetic such as apraclonidine or brimonidine tartrate, or a topical miotic such as pilocarpine, given either as monotherapy or as combination therapy.}} However, due to its side effects, it is no longer typically used for long-term management.{{cite journal | vauthors = Lusthaus J, Goldberg I | title = Current management of glaucoma | journal = The Medical Journal of Australia | volume = 210 | issue = 4 | pages = 180–187 | date = March 2019 | pmid = 30767238 | doi = 10.5694/mja2.50020 | quote = Pilocarpine is no longer routinely used for long term IOP control due to a poor side effect profile | s2cid = 73438590 }} Onset of effects with the drops is typically within an hour and lasts for up to a day.{{cite web |title=Pilocarpine |url=https://www.drugs.com/monograph/pilocarpine.html|publisher=The American Society of Health-System Pharmacists|access-date=8 December 2016|url-status=live|archive-url=https://web.archive.org/web/20161228200133/https://www.drugs.com/monograph/pilocarpine.html|archive-date=28 December 2016}} By mouth it is used for dry mouth as a result of Sjögren syndrome or radiation therapy.{{cite book| vauthors = Hamilton R |title=Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition|date=2015|publisher=Jones & Bartlett Learning|isbn=9781284057560|page=415}}
Common side effects of the eye drops include irritation of the eye, increased tearing, headache, and blurry vision. Other side effects include allergic reactions and retinal detachment. Use is generally not recommended during pregnancy.{{cite web|title=Pilocarpine ophthalmic Use During Pregnancy |url=https://www.drugs.com/pregnancy/pilocarpine-ophthalmic.html|website=Drugs.com |access-date=28 December 2016|url-status=live|archive-url=https://web.archive.org/web/20161228200001/https://www.drugs.com/pregnancy/pilocarpine-ophthalmic.html|archive-date=28 December 2016}} Pilocarpine is in the miotics family of medication.{{cite book|title=British national formulary : BNF 69|date=2015|publisher=British Medical Association|isbn=9780857111562|page=769|edition=69}} It works by activating cholinergic receptors of the muscarinic type which cause the trabecular meshwork to open and the aqueous humor 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.{{cite book| vauthors = Sneader W |title=Drug Discovery: A History|date=2005|publisher=John Wiley & Sons|isbn=978-0-471-89979-2 |page=98|url=https://books.google.com/books?id=Cb6BOkj9fK4C&pg=PA98|url-status=live|archive-url=https://web.archive.org/web/20161229100153/https://books.google.ca/books?id=Cb6BOkj9fK4C&pg=PA98|archive-date=2016-12-29}}{{cite journal | vauthors = Rosin A | title = [Pilocarpine. A miotic of choice in the treatment of glaucoma has passed 110 years of use] | language = ro | journal = Oftalmologia | volume = 35 | issue = 1 | pages = 53–55 | year = 1991 | pmid = 1811739 }}{{cite journal | vauthors = Holmstedt B, Wassén SH, Schultes RE | title = Jaborandi: an interdisciplinary appraisal | journal = Journal of Ethnopharmacology | volume = 1 | issue = 1 | pages = 3–21 | date = January 1979 | pmid = 397371 | doi = 10.1016/0378-8741(79)90014-x }} It is on the World Health Organization's List of Essential Medicines.{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }} It was originally made from the South American plant Pilocarpus.
Medical uses
Pilocarpine stimulates the secretion of large amounts of saliva and sweat.{{cite web |title=Pilocarpine |url=https://www.nlm.nih.gov/medlineplus/druginfo/meds/a608039.html |url-status=live |archive-url=https://web.archive.org/web/20100306135234/http://www.nlm.nih.gov/medlineplus/druginfo/meds/a608039.html |archive-date=2010-03-06 | work = MedLinePlus | publisher = U.S. National Library of Medicine }} It is used to prevent or treat dry mouth, particularly in Sjögren syndrome, but also as a side effect of radiation therapy for head and neck cancer.{{cite journal | vauthors = Yang WF, Liao GQ, Hakim SG, Ouyang DQ, Ringash J, Su YX | title = Is Pilocarpine Effective in Preventing Radiation-Induced Xerostomia? A Systematic Review and Meta-analysis | journal = International Journal of Radiation Oncology, Biology, Physics | volume = 94 | issue = 3 | pages = 503–511 | date = March 2016 | pmid = 26867879 | doi = 10.1016/j.ijrobp.2015.11.012 | hdl-access = free | hdl = 10722/229069 }}
It may be used to help differentiate Adie syndrome from other causes of unequal pupil size.{{Cite book|url=https://books.google.com/books?id=D9GfBwAAQBAJ&pg=PA812|title=Kanski's Clinical Ophthalmology E-Book: A Systematic Approach| vauthors = Kanski JJ, Bowling B |date=2015-03-24|publisher=Elsevier Health Sciences|isbn=978-0-7020-5574-4 |page = 812}}{{cite book |doi=10.1016/B978-0-7506-9322-6.50011-8 |chapter=Drugs Affecting the Autonomic Nervous System |title=Clinical Ocular Pharmacology |date=1989 | vauthors = Jaanus SD, Pagano VT, Bartlett JD |pages=69–148 |isbn=978-0-7506-9322-6 }}
It may be used to treat a form of dry eye called aqueous deficient dry eye (ADDE){{cite book | title = Cornea E-Book | vauthors = Mannis MJ, Holland EJ | publisher = Elsevier Health Sciences | date = September 2016 | chapter = Chapter 33: Dry Eye | chapter-url = https://books.google.com/books?id=ywwlDQAAQBAJ&pg=388 | page = 388 | isbn = 978-0-323-35758-6 | oclc = 960165358 }}
=Surgery=
Pilocarpine is sometimes used immediately before certain types of corneal grafts and cataract surgery.{{cite thesis | vauthors = Parker J |title=Descemet Membrane Endothelial Keratoplasty (DMEK): A Review |date=2017 |publisher=Leiden University |hdl=1887/50484 }}{{cite book | vauthors = Ahmed E |title=Comprehensive Manual of Ophthalmology |date=2010 |publisher=JP Medical Ltd |isbn=978-93-5025-175-1 |page=345 |url=https://books.google.com/books?id=6prpFb-UcKAC&pg=PA345 }} 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 lenses; the use of pilocarpine would reduce the size of the pupils, partially relieving these symptoms.{{Dubious|date=September 2019}} The most common concentration for this use is pilocarpine 1%.{{citation needed|date=September 2019}} Pilocarpine is shown to be just as effective as apraclonidine in preventing intraocular pressure spikes after laser trabeculoplasty.{{cite journal | vauthors = Zhang L, Weizer JS, Musch DC | title = Perioperative medications for preventing temporarily increased intraocular pressure after laser trabeculoplasty | journal = The Cochrane Database of Systematic Reviews | volume = 2017 | issue = 2 | pages = CD010746 | date = February 2017 | pmid = 28231380 | pmc = 5477062 | doi = 10.1002/14651858.CD010746.pub2 }}
= Presbyopia =
In 2021, the US Food and Drug Administration (FDA) approved pilocarpine hydrochloride as an eye drop treatment for presbyopia, 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.{{cite journal | vauthors = Grzybowski A, Ruamviboonsuk V | title = Pharmacological Treatment in Presbyopia | journal = Journal of Clinical Medicine | volume = 11 | issue = 5 | page = 1385 | date = March 2022 | pmid = 35268476 | pmc = 8910925 | doi = 10.3390/jcm11051385 | doi-access = free }}
=Other=
Pilocarpine is used to stimulate sweat glands in a sweat test to measure the concentration of chloride and sodium that is excreted in sweat. It is used to diagnose cystic fibrosis.{{Cite book|url=https://books.google.com/books?id=r6IsDwAAQBAJ&pg=PT3|title=Chemistry and Synthesis of Medicinal Agents: (Expanding Knowledge of Drug Chemistry)| vauthors = Prasad RK |date=2017-07-11|publisher=BookRix|isbn=978-3-7438-2141-5}}
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 secretion, bronchospasm, bradycardia, vasodilation, and diarrhea. Eye drops can result in brow ache and chronic use in miosis. It can also cause temporary blurred vision or darkness of vision, temporary shortsightedness, hyphema 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 and causes it to contract. When the ciliary muscle contracts, it opens the trabecular meshwork through increased tension on the scleral spur. This action facilitates the rate that aqueous humor leaves the eye to decrease intraocular pressure. Paradoxically, when pilocarpine induces this ciliary muscle contraction (known as an accommodative spasm) it causes the eye's lens 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 intraocular pressure.{{cite book |doi=10.1016/B978-0-7020-5193-7.00073-X |chapter=Laser Peripheral Iridoplasty |title=Glaucoma |date=2015 | vauthors = Teekhasaenee C |pages=716–721 |isbn=978-0-7020-5193-7 }}
Society and culture
= Preparation =
Plants in the genus Pilocarpus 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.{{cite journal|title=Production of Pilocarpine in Callus of Jaborandi (Pilocarpus microphyllus Stapf)|jstor=4293939| vauthors = De Abreu IN, Sawaya AC, Eberlin MN, Mazzafera P |journal=In Vitro Cellular & Developmental Biology - Plant|volume=41|issue=6|date=November–December 2005|pages=806–811|publisher=Society for In Vitro Biology|doi=10.1079/IVP2005711|bibcode=2005IVCDB..41..806A |s2cid=26058596}}
Pilocarpine is extracted from the leaves of Pilocarpus microphyllus in a multi-step process : the sample is moistened with dilute sodium hydroxide to transform the alkaloid into its free-base form then extracted using chloroform or a suitable organic solvant. Pilocarpine can then be further purified by re-extracting the resulting solution with aqueous sulfuric acid then readjusting the pH to basic using ammonia and a final extraction by chloroform.{{cite journal | vauthors = Avancini G, Abreu IN, Saldaña MD, Mohamed RS, Mazzafera P | title = Induction of pilocarpine formation in jaborandi leaves by salicylic acid and methyljasmonate | journal = Phytochemistry | volume = 63 | issue = 2 | pages = 171–175 | date = May 2003 | pmid = 12711138 | doi = 10.1016/S0031-9422(03)00102-X | bibcode = 2003PChem..63..171A }}{{cite journal | vauthors = Sawaya AC, Abreu IN, Andreazza NL, Eberlin MN, Mazzafera P | title = HPLC-ESI-MS/MS of imidazole alkaloids in Pilocarpus microphyllus | journal = Molecules | volume = 13 | issue = 7 | pages = 1518–1529 | date = July 2008 | pmid = 18719522 | doi = 10.3390/molecules13071518 | doi-access = free | pmc = 6245396 }}{{cite book |doi=10.1201/b15129-14 |chapter=Glaucoma |title=Eye Care in Developing Nations | editor = Fourth | date=2007 |pages=99–116 |isbn=978-1-84076-103-0 | vauthors = Schwab L |doi-broken-date=2024-11-12 }}
It can also be synthesized from 2-ethyl-3-carboxy-2-butyrolactone in a 8 steps process from the acyl chloride (by treatment with thionyl chloride) via a Arndt–Eistert reaction with diazomethane then by treatment with potassium phthalimide and potassium thiocyanate.
= Brand names =
Pilocarpine is available under several brand 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 in rodents, commonly rats, as a means to study the disorder's physiology and to examine different treatments.{{cite thesis|title=Immunohistochemical investigations of the neuronal changes induced by chronic recurrent seizures in a pilocarpine rodent model of temporal lobe epilepsy| doi = 10.14232/phd.9734 |publisher=University of Szeged| vauthors = Károly N | date = 2018 |doi-access=free }}{{cite journal | vauthors = Morimoto K, Fahnestock M, Racine RJ | title = Kindling and status epilepticus models of epilepsy: rewiring the brain | journal = Progress in Neurobiology | volume = 73 | issue = 1 | pages = 1–60 | date = May 2004 | pmid = 15193778 | doi = 10.1016/j.pneurobio.2004.03.009 | s2cid = 36849482 }} Smaller doses may be used to induce salivation in order to collect samples of saliva, for instance, to obtain information about IgA antibodies.
References
{{Reflist}}
External links
{{wikisource|1911 Encyclopædia Britannica/Pilocarpine|Pilocarpine}}
{{Antiglaucoma preparations and miotics}}
{{Muscarinic acetylcholine receptor modulators}}
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Category:Alkaloids found in Rutaceae
Category:Drugs developed by Novartis
Category:Drugs developed by Pfizer