Revision as of 13:06, 5 December 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Saving copy of the {{drugbox}} taken from revid 462917721 of page Pilocarpine for the Chem/Drugbox validation project (updated: 'DrugBank'). |
Latest revision as of 03:01, 7 January 2025 edit Whywhenwhohow (talk | contribs)Autopatrolled, Extended confirmed users, Pending changes reviewers49,178 edits infobox, refs, description, links, templates; remove text without citation |
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{{Short description|Medication used to treat glaucoma and dry mouth}} |
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{{ambox | text = This page contains a copy of the infobox ({{tl|drugbox}}) taken from revid of page ] with values updated to verified values.}} |
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{{Use dmy dates|date=January 2025}} |
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{{Drugbox |
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{{cs1 config |name-list-style=vanc |display-authors=6}} |
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{{Infobox drug |
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| verifiedrevid = 412575930 |
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| Watchedfields = changed |
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| IUPAC_name = (3''S'',4''R'')- 3-ethyl- 4-((1-methyl- 1''H''-imidazol- 5-yl) methyl)dihydrofuran- 2(3''H'')-one |
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| verifiedrevid = 464206617 |
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| image = Pilocarpine Structural Formulae.png |
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| image = Pilocarpine.svg |
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| width = 180 |
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| alt = |
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| image2 = Pilocarpine ball-and-stick model.png |
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| width2 = |
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| alt2 = |
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| caption = |
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<!--Clinical data--> |
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<!-- Clinical data --> |
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| tradename = Salagen |
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| pronounce = |
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| tradename = Pilopine HS, others |
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| Drugs.com = {{drugs.com|monograph|pilocarpine}} |
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| Drugs.com = {{drugs.com|monograph|pilocarpine}} |
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| MedlinePlus = a608039 |
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| MedlinePlus = a608039 |
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| DailyMedID = Pilocarpine |
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| pregnancy_category = C |
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| pregnancy_AU = B3 |
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| pregnancy_AU_comment = |
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| pregnancy_category = |
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| routes_of_administration = ], ] |
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| class = {{plainlist| |
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*], |
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*]<ref name=AHFS2016/>}} |
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| ATC_prefix = N07 |
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| ATC_suffix = AX01 |
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| ATC_supplemental = {{ATC|S01|EB01}} |
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<!-- Legal status --> |
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| legal_AU = S4 |
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| legal_AU_comment = |
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| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F --> |
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| legal_BR_comment = |
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| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII --> |
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| legal_CA_comment = |
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| legal_DE = <!-- Anlage I, II, III or Unscheduled --> |
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| legal_DE_comment = |
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| legal_NZ = <!-- Class A, B, C --> |
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| legal_NZ_comment = |
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| legal_UK = POM |
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| legal_UK_comment = |
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| legal_US = Rx-only |
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| legal_US = Rx-only |
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| legal_US_comment = <ref name="Vuity FDA label">{{cite web | title=Vuity- pilocarpine hydrochloride solution/ drops | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8d806897-8a2a-4518-8c68-0ec3b778de50 | access-date=19 December 2021}}</ref> |
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| routes_of_administration = ], ] |
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| legal_EU = |
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| legal_EU_comment = |
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| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV --> |
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| legal_UN_comment = |
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| legal_status = <!-- For countries not listed above --> |
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<!--Pharmacokinetic data--> |
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<!-- Pharmacokinetic data --> |
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| bioavailability = |
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| bioavailability = |
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| protein_bound = |
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| protein_bound = |
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| metabolism = |
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| metabolism = |
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| metabolites = |
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| elimination_half-life = {{Reference necessary|1=0.76 hours (5 mg), 1.35 hours (10 mg)|date=April 2011}} |
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| onset = |
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| elimination_half-life = 0.76 hours (5 mg), 1.35 hours (10 mg)<ref>{{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 }}</ref> |
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| duration_of_action = |
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| excretion = urine |
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| excretion = urine |
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<!--Identifiers--> |
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<!-- Identifiers --> |
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| CASNo_Ref = {{cascite|correct|CAS}} |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| CAS_number = 92-13-7 |
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| CAS_number = 92-13-7 |
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| CAS_number2 = 54-71-7 |
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| CAS_supplemental = <br/>54-71-7 (hydrochloride) <!-- Also CAS verified --> |
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| ATC_prefix = N07 |
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| ATC_suffix = AX01 |
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| ATC_supplemental = {{ATC|S01|EB01}} |
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| PubChem = 5910 |
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| PubChem = 5910 |
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| IUPHAR_ligand = 305 |
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| IUPHAR_ligand = 305 |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| UNII = 01MI4Q9DI3 |
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| UNII = 01MI4Q9DI3 |
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| UNII2 = 0WW6D218XJ |
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| KEGG_Ref = {{keggcite|correct|kegg}} |
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| KEGG_Ref = {{keggcite|correct|kegg}} |
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| KEGG = D00525 |
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| KEGG = D00525 |
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| KEGG2 = D02200 |
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| ChEBI_Ref = {{ebicite|changed|EBI}} |
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| ChEBI_Ref = {{ebicite|correct|EBI}} |
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| ChEBI = 8207 |
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| ChEBI = 8207 |
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| ChEMBL_Ref = {{ebicite|correct|EBI}} |
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| ChEMBL_Ref = {{ebicite|correct|EBI}} |
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| ChEMBL = 550 |
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| ChEMBL = 550 |
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| NIAID_ChemDB = |
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| synonyms = |
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<!--Chemical data--> |
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<!-- Chemical and physical data --> |
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| IUPAC_name = (3''S'',4''R'')-3-Ethyl-4-((1-methyl-1''H''-imidazol-5-yl)methyl)dihydrofuran-2(3''H'')-one |
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| C=11 | H=16 | N=2 | O=2 |
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| C = 11 |
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| molecular_weight = 208.257 g/mol |
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| H = 16 |
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| smiles = O=C2OC(Cc1n(cnc1)C)2CC |
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| N = 2 |
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| InChI = 1/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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| O = 2 |
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| InChIKey = QCHFTSOMWOSFHM-WPRPVWTQBQ |
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| SMILES = O=C2OC(Cc1n(cnc1)C)2CC |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| 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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| 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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| StdInChI_comment = |
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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChIKey = QCHFTSOMWOSFHM-WPRPVWTQSA-N |
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| StdInChIKey = QCHFTSOMWOSFHM-WPRPVWTQSA-N |
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| density = |
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}} |
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}} |
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<!-- Definition and medical uses --> |
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'''Pilocarpine''', sold under the brand name '''Pilopine HS''' among others, is a ] ] originally extracted from plants of the ] genus.<ref name="Vardanyan_2006">{{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 }}</ref> It is used as a medication to reduce ] and treat ].<ref name="AHFS2016" /><ref name="Tar2019">{{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 }}</ref> As an ] it is used to manage ] until surgery can be performed, ], ], and to ] after dilation.<ref name="AHFS2016" /><ref name="WHO2008">{{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 }}</ref><ref>{{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.}}</ref> However, due to its side effects, it is no longer typically used for long-term management.<ref>{{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 }}</ref> Onset of effects with the drops is typically within an hour and lasts for up to a day.<ref name="AHFS2016">{{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}}</ref> By mouth it is used for dry mouth as a result of ] or ].<ref name="Ric2015">{{cite book| vauthors = Hamilton R |title=Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition|date=2015|publisher=Jones & Bartlett Learning|isbn=9781284057560|page=415}}</ref> |
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<!-- Side effects and mechanism --> |
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Common side effects of the eye drops include irritation of the eye, increased tearing, headache, and blurry vision.<ref name=AHFS2016/> Other side effects include ] and ].<ref name=AHFS2016/> Use is generally not recommended during ].<ref>{{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}}</ref> Pilocarpine is in the ] family of medication.<ref name=BNF69>{{cite book|title=British national formulary : BNF 69|date=2015|publisher=British Medical Association|isbn=9780857111562|page=769|edition=69}}</ref> It works by activating ] of the ] which cause the ] to open and the ] to drain from the eye.<ref name=AHFS2016/> |
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<!-- History and culture --> |
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Pilocarpine was isolated in 1874 by Hardy and Gerrard and has been used to treat glaucoma for more than 100 years.<ref name=Sn2005>{{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}}</ref><ref>{{cite journal | vauthors = Rosin A | title = | language = ro | journal = Oftalmologia | volume = 35 | issue = 1 | pages = 53–55 | year = 1991 | pmid = 1811739 }}</ref><ref>{{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 }}</ref> It is on the ].<ref name="WHO21st">{{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 }}</ref> It was originally made from the South American plant '']''.<ref name=Sn2005/> |
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== Medical uses == |
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Pilocarpine stimulates the secretion of large amounts of ] and ].<ref>{{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 }}</ref> It is used to prevent or treat ], particularly in ], but also as a side effect of ] for ].<ref>{{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 }}</ref> |
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It may be used to help differentiate ] from other causes of ].<ref>{{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}}</ref><ref>{{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 }}</ref> |
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It may be used to treat a form of ] called ''aqueous deficient dry eye (ADDE)''<ref>{{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 }}</ref> |
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===Surgery=== |
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Pilocarpine is sometimes used immediately before ] and ].<ref>{{cite thesis | vauthors = Parker J |title=Descemet Membrane Endothelial Keratoplasty (DMEK): A Review |date=2017 |publisher=Leiden University |hdl=1887/50484 }}</ref><ref>{{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 }}</ref> 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 ]es; 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 ] in preventing intraocular pressure spikes after ].<ref name="Zhang">{{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 }}</ref> |
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=== Presbyopia === |
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In 2021, the US ] (FDA) approved pilocarpine hydrochloride as an ] treatment for ], age-related difficulty with near-in vision. It works by causing the pupils to constrict, increasing ], similar to the effect of ].<ref>{{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 }}</ref><ref name="Vuity FDA label" /> |
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===Other=== |
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Pilocarpine is used to stimulate sweat glands in a ] to measure the ] of ] and ] that is excreted in sweat. It is used to diagnose ].<ref>{{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}}</ref> |
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== Adverse effects == |
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Use of pilocarpine may result in a range of adverse effects, most of them related to its ] action as a muscarinic receptor agonist. Pilocarpine has been known to cause excessive salivation, sweating, bronchial ] secretion, ], ], ], and ]. Eye drops can result in brow ] and chronic use in ]. It can also cause temporary blurred vision or darkness of vision, temporary shortsightedness, ] and retinal detachment. |
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==Pharmacology== |
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Pilocarpine is a drug that acts as a muscarinic receptor agonist. It acts on a subtype of muscarinic receptor (]) found on the ], causing the muscle to contract - resulting in pupil constriction (]). Pilocarpine also acts on the ] and causes it to contract. When the ciliary muscle contracts, it opens the ] through increased tension on the ]. This action facilitates the rate that ] leaves the ] to decrease ]. Paradoxically, when pilocarpine induces this ciliary muscle contraction (known as an ]) it causes the eye's ] 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 ]. Narrowing of the anterior chamber angle increases the risk of increased ].<ref>{{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 }}</ref> |
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==Society and culture== |
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=== Preparation === |
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Plants in the genus '']'' are the only known sources of pilocarpine, and commercial production is derived entirely from the leaves of '']'' (Maranham Jaborandi). This genus grows only in South America, and ''Pilocarpus microphyllus'' is native to several states in northern Brazil.<ref name="ivcdb">{{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=]|doi=10.1079/IVP2005711|s2cid=26058596}}</ref> |
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Pilocarpine is extracted from the leaves of Pilocarpus microphyllus in a multi-step process : the sample is moistened with dilute ] to transform the alkaloid into its free-base form then extracted using ] or a suitable organic solvant. Pilocarpine can then be further purified by re-extracting the resulting solution with aqueous ] then readjusting the pH to basic using ] and a final extraction by chloroform.<ref>{{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 }}</ref><ref>{{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 }}</ref><ref name=Sch2007>{{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 }}</ref> |
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It can also be synthesized from 2-ethyl-3-carboxy-2-butyrolactone in a 8 steps process from the acyl chloride (by treatment with ]) via a ] with ] then by treatment with ] and ].<ref name = "Vardanyan_2006" /> |
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=== Brand names === |
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Pilocarpine is available under several brand names such as: Diocarpine (Dioptic), Isopto Carpine (]), 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). |
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== Research == |
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Pilocarpine is used to induce chronic ] in ]s, commonly ]s, as a means to study the disorder's physiology and to examine different treatments.<ref name = "Károly_2018">{{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 }}</ref><ref>{{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 }}</ref> Smaller doses may be used to induce salivation in order to collect samples of ], for instance, to obtain information about ] antibodies. |
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== References == |
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{{Reflist}} |
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== External links == |
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{{wikisource|1911 Encyclopædia Britannica/Pilocarpine|Pilocarpine}} |
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