Glycopyrronium bromide

{{Short description|Anticholinergic}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Infobox drug | image = Glycopyrronium bromide.svg | image_class = skin-invert-image | Verifiedfields = changed | INN = Glycopyrronium | caption2 = 3D representation of a glycopyrronium bromide molecule | verifiedrevid = 461122867 | width = | alt = | caption = Molecular structure of glycopyrronium bromide | image2 = Glycopyrronium bromide 3D.png | USAN = glycopyrrolate

| pronounce = {{IPAc-en|ˌ|ɡ|l|aɪ|k|əʊ|p|aɪ|ˈ|r|əʊ|n|i|ʌ|m| |ˈ|b|r|oʊ|m|aɪ|d}}

{{respell|gly-koh-py-ROH-nee-um BROH-myd}} | tradename = Robinul, Cuvposa, Seebri, others | Drugs.com = {{drugs.com|monograph|glycopyrrolate}} | MedlinePlus = a602014 | DailyMedID = Glycopyrrolate | pregnancy_AU = B2 | pregnancy_AU_comment = | pregnancy_category = | routes_of_administration = By mouth, intravenous, inhalation, topical, injection, subcutaneous | class = Antimuscarinic (peripherally-selective) | ATC_prefix = A03 | ATC_suffix = AB02 | ATC_supplemental = {{ATC|D11|AA01}} {{ATC|R03|BB06}}

| legal_AU = S3 / S4 | legal_AU_comment = | legal_BR =  | legal_BR_comment = | legal_CA = Rx-only | legal_CA_comment = <ref>{{cite web | title= Neurological therapies | website=Health Canada | date=9 May 2018 | url=https://www.canada.ca/en/services/health/drug-health-products/drug-medical-device-highlights-2017/approved-drugs/neurological-therapies.html | access-date=13 April 2024}}</ref> | legal_DE =  | legal_DE_comment = | legal_NZ =  | legal_NZ_comment = | legal_UK = POM | legal_UK_comment = | legal_US = Rx-only | legal_US_comment = <ref name="Robinul FDA label">{{cite web | title=Robinul- glycopyrrolate tablet Robinul Forte- glycopyrrolate tablet | website=DailyMed | date=1 June 2021 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=94fb029a-6371-4b1c-89de-35e8209c7cab | access-date=20 June 2022}}</ref><ref>{{cite web | title=Dartisla ODT- glycopyrrolate orally disintegrating tablets tablet, orally disintegrating | website=DailyMed | date=9 December 2021 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=52daf47e-7ba3-4105-be7f-27001a87e16e | access-date=20 June 2022}}</ref> | legal_EU = Rx-only | legal_EU_comment = <ref name="Seebri Breezhaler EPAR" /><ref name="Tovanor Breezhaler EPAR" /><ref name="Enurev Breezhaler EPAR" /><ref name="Sialanar EPAR">{{cite web | title=Sialanar EPAR | website=European Medicines Agency | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/sialanar | access-date=29 January 2023}} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref> | legal_UN =  | legal_UN_comment = | legal_status = Rx-only

| index2_label = as cation | CAS_number_Ref = {{cascite|correct|CAS}} | CAS_number = 51186-83-5 | CAS_number2 = 596-51-0 | CAS_supplemental = | PubChem = 3494 | PubChem2 = 11693 | IUPHAR_ligand = 7459 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DBSALT001183 | DrugBank2 = DB00986 | ChemSpiderID = 11201 | ChemSpiderID2 = 3374 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = V92SO9WP2I | UNII2 = A14FB57V1D | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D00540 | KEGG2 = D10938 | ChEBI = 90972 | ChEMBL_Ref = {{ebicite|changed|EBI}} | ChEMBL = 1201027 | ChEMBL2 = 1201335 | NIAID_ChemDB = | PDB_ligand = | synonyms =  | IUPAC_name = 3-[2-Cyclopentyl(hydroxy)phenylacetoxy]-1,1-dimethylpyrrolidinium bromide | C = 19 | H = 28 | Br = 1 | N = 1 | O = 3 | SMILES = C[N+]1(CCC(C1)OC(=O)C(C2CCCC2)(C3=CC=CC=C3)O)C.[Br-] | SMILES2 = C[N+]1(CCC(C1)OC(=O)C(C2CCCC2)(C3=CC=CC=C3)O)C | StdInChI = 1S/C19H28NO3.BrH/c1-20(2)13-12-17(14-20)23-18(21)19(22,16-10-6-7-11-16)15-8-4-3-5-9-15;/h3-5,8-9,16-17,22H,6-7,10-14H2,1-2H3;1H/q+1;/p-1 | StdInChI2 = 1S/C19H28NO3/c1-20(2)13-12-17(14-20)23-18(21)19(22,16-10-6-7-11-16)15-8-4-3-5-9-15/h3-5,8-9,16-17,22H,6-7,10-14H2,1-2H3/q+1 | StdInChIKey = VPNYRYCIDCJBOM-UHFFFAOYSA-M | StdInChIKey2 = ANGKOCUUWGHLCE-UHFFFAOYSA-N | density = | density_notes = | melting_point = | melting_high = | melting_notes = | boiling_point = | boiling_notes = | solubility = | sol_units = | specific_rotation = }}

'''Glycopyrronium bromide''' is a medication of the muscarinic anticholinergic group.<ref name="Sialanar EPAR" /> It does not cross the blood–brain barrier and consequently has few to no central effects. It can be administered orally,<ref>{{cite web | title=Glycopyrrolate Oral Inhalation | website=MedlinePlus | url=https://medlineplus.gov/druginfo/meds/a618016.html | access-date=20 June 2022 | archive-date=17 August 2021 | archive-url=https://web.archive.org/web/20210817020822/https://medlineplus.gov/druginfo/meds/a618016.html | url-status=live }}</ref> intravenously, topically,<ref>{{cite web |title=Glycopyrronium Topical |url=https://medlineplus.gov/druginfo/meds/a618046.html |url-status=live |archive-url=https://web.archive.org/web/20210817175947/https://medlineplus.gov/druginfo/meds/a618046.html |archive-date=17 August 2021 |access-date=20 June 2022 |website=MedlinePlus}}</ref> or via inhalation.<ref name="Seebri Breezhaler EPAR" /><ref name="Tovanor Breezhaler EPAR" /><ref name="Enurev Breezhaler EPAR" /> It is a synthetic quaternary ammonium compound.<ref name="Robinul FDA label" /> The cation, which is the active moiety, is called '''glycopyrronium''' (INN)<ref name="pmid17459043">{{cite journal | vauthors = Bajaj V, Langtry JA | title = Use of oral glycopyrronium bromide in hyperhidrosis | journal = The British Journal of Dermatology | volume = 157 | issue = 1 | pages = 118–121 | date = July 2007 | pmid = 17459043 | doi = 10.1111/j.1365-2133.2007.07884.x | s2cid = 29080876 }}</ref> or '''glycopyrrolate''' (USAN).

The most common side effects include irritability, flushing, nasal congestion, reduced secretions in the airways, dry mouth, constipation, diarrhea, nausea and vomiting, and urinary retention.<ref name="Sialanar EPAR" />

In September 2012, glycopyrronium was approved for medical use in the European Union.<ref name="Seebri Breezhaler EPAR" /> In June 2018, glycopyrronium was approved by the U.S. Food and Drug Administration (FDA) to treat excessive underarm sweating, becoming the first drug developed specifically to reduce excessive sweating.<ref>{{Cite news|url=https://apnews.com/21f28f1327ca4f9497cf878cc0229444|title=FDA OKs first drug made to reduce excessive sweating|work=AP News|access-date=2018-07-02|archive-date=2018-07-02|archive-url=https://web.archive.org/web/20180702233319/https://apnews.com/21f28f1327ca4f9497cf878cc0229444|url-status=live}}</ref> It is on the World Health Organization's List of Essential Medicines.<ref name="WHO22nd">{{cite book | title = World Health Organization model list of essential medicines: 22nd list (2021) | year = 2021 | hdl = 10665/345533 | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2021.02 | hdl-access=free }}</ref>

==Medical uses== Glycopyrronium was first used in 1961 to treat peptic ulcers. Since 1975, intravenous glycopyrronium has been used before surgery to reduce salivary, tracheobronchial, and pharyngeal secretions.<ref name=chabicovsky/> It is also used in conjunction with neostigmine, a neuromuscular blocking reversal agent, to prevent neostigmine's muscarinic effects such as bradycardia.<ref>{{cite journal | vauthors = Howard J, Wigley J, Rosen G, D'mello J | title = Glycopyrrolate: It's time to review | journal = Journal of Clinical Anesthesia | volume = 36 | pages = 51–53 | date = February 2017 | pmid = 28183573 | doi = 10.1016/j.jclinane.2016.09.013 }}</ref> It can be administered to raise the heart rate in reflex bradycardia as a result of a vasovagal reaction, which often will also increase the blood pressure.<ref name="Gallanosa_2023">{{cite book | vauthors = Gallanosa A, Stevens JB, Quick J | chapter = Glycopyrrolate | date = June 2023 | title = StatPearls [Internet] | location = Treasure Island (FL) | publisher = StatPearls Publishing | pmid = 30252291 | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK526035/ | access-date=September 13, 2024 }}</ref>

It is also used to reduce excessive saliva (sialorrhea),<ref name="Sialanar EPAR" /><ref name="pmid11115305">{{cite journal | vauthors = Mier RJ, Bachrach SJ, Lakin RC, Barker T, Childs J, Moran M | title = Treatment of sialorrhea with glycopyrrolate: A double-blind, dose-ranging study | journal = Archives of Pediatrics & Adolescent Medicine | volume = 154 | issue = 12 | pages = 1214–1218 | date = December 2000 | pmid = 11115305 | doi = 10.1001/archpedi.154.12.1214 | url = http://archpedi.ama-assn.org/cgi/pmidlookup?view=long&pmid=11115305 | access-date = 2008-11-26 | url-status = live | doi-access = free | archive-url = https://archive.today/20110810032036/http://archpedi.ama-assn.org/cgi/pmidlookup?view=long&pmid=11115305 | archive-date = 2011-08-10 | url-access = subscription }}</ref><ref name="pmid12398577">{{cite journal | vauthors = Tscheng DZ | title = Sialorrhea - therapeutic drug options | journal = The Annals of Pharmacotherapy | volume = 36 | issue = 11 | pages = 1785–1790 | date = November 2002 | pmid = 12398577 | doi = 10.1345/aph.1C019 | s2cid = 45799443 }}{{dead link|date=October 2017 |bot=InternetArchiveBot |fix-attempted=yes }}</ref><ref name="pmid10534970">{{cite journal | vauthors = Olsen AK, Sjøgren P | title = Oral glycopyrrolate alleviates drooling in a patient with tongue cancer | journal = Journal of Pain and Symptom Management | volume = 18 | issue = 4 | pages = 300–302 | date = October 1999 | pmid = 10534970 | doi = 10.1016/S0885-3924(99)00080-9 | doi-access = free }}</ref> and to treat Ménière's disease.<ref>{{cite journal|title=Medical therapy in Ménière's disease|journal=Audiological Medicine| vauthors = Maria SA, Claudia C, Pamela G, Andrea C, Roberto A |date=1 December 2012|volume=10|issue=4|pages=171–177|doi=10.3109/1651386X.2012.718413|s2cid=72380413}}</ref>

It has been used topically and orally to treat hyperhidrosis, in particular, gustatory hyperhidrosis and generalized hyperhidrosis.<ref name="pmid12950111">{{cite journal | vauthors = Kim WO, Kil HK, Yoon DM, Cho MJ | title = Treatment of compensatory gustatory hyperhidrosis with topical glycopyrrolate | journal = Yonsei Medical Journal | volume = 44 | issue = 4 | pages = 579–582 | date = August 2003 | pmid = 12950111 | doi = 10.3349/ymj.2003.44.4.579 | doi-access = free }}</ref><ref name="pmid18294315">{{cite journal | vauthors = Kim WO, Kil HK, Yoon KB, Yoon DM | title = Topical glycopyrrolate for patients with facial hyperhidrosis | journal = The British Journal of Dermatology | volume = 158 | issue = 5 | pages = 1094–1097 | date = May 2008 | pmid = 18294315 | doi = 10.1111/j.1365-2133.2008.08476.x | s2cid = 39870296 }}</ref>

When inhaled, it is used to treat chronic obstructive pulmonary disease (COPD).<ref name="Seebri Breezhaler EPAR">{{cite web | title=Seebri Breezhaler EPAR | website=European Medicines Agency (EMA) | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/seebri-breezhaler | access-date=28 February 2020 | archive-date=29 February 2020 | archive-url=https://web.archive.org/web/20200229101656/https://www.ema.europa.eu/en/medicines/human/EPAR/seebri-breezhaler | url-status=live }}</ref><ref name="Tovanor Breezhaler EPAR">{{cite web | title=Tovanor Breezhaler EPAR | website=European Medicines Agency (EMA) | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/tovanor-breezhaler | access-date=28 February 2020 | archive-date=29 February 2020 | archive-url=https://web.archive.org/web/20200229101658/https://www.ema.europa.eu/en/medicines/human/EPAR/tovanor-breezhaler | url-status=live }}</ref><ref name="Enurev Breezhaler EPAR">{{cite web | title=Enurev Breezhaler EPAR | website=European Medicines Agency | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/enurev-breezhaler | access-date=29 January 2023}}</ref> Doses for inhalation are much lower than oral ones, so that swallowing a dose will not have an effect.<ref>{{cite web|url=http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002430/WC500133769.pdf|title=EPAR – Product information for Seebri Breezhaler|publisher=European Medicines Agency|date=28 September 2012|access-date=4 February 2017|archive-date=30 July 2018|archive-url=https://web.archive.org/web/20180730210441/http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002430/WC500133769.pdf|url-status=live}}</ref><ref name="pmid8834341">{{cite journal | vauthors = Tzelepis G, Komanapolli S, Tyler D, Vega D, Fulambarker A | title = Comparison of nebulized glycopyrrolate and metaproterenol in chronic obstructive pulmonary disease | journal = The European Respiratory Journal | volume = 9 | issue = 1 | pages = 100–103 | date = January 1996 | pmid = 8834341 | doi = 10.1183/09031936.96.09010100 | doi-access = free }}</ref>

==Side effects== Dry mouth, urinary retention, headaches, vomiting, diarrhea, constipation, and blurry vision are possible side effects of the medication.<ref name=chabicovsky/>

==Pharmacology== ===Mechanism of action=== Glycopyrronium competitively blocks muscarinic receptors,<ref name=chabicovsky>{{cite journal | vauthors = Chabicovsky M, Winkler S, Soeberdt M, Kilic A, Masur C, Abels C | title = Pharmacology, toxicology and clinical safety of glycopyrrolate | journal = Toxicology and Applied Pharmacology | volume = 370 | pages = 154–169 | date = May 2019 | pmid = 30905688 | doi = 10.1016/j.taap.2019.03.016 | bibcode = 2019ToxAP.370..154C | s2cid = 85498396 }}</ref><ref name="pmid10385241">{{cite journal | vauthors = Haddad EB, Patel H, Keeling JE, Yacoub MH, Barnes PJ, Belvisi MG | title = Pharmacological characterization of the muscarinic receptor antagonist, glycopyrrolate, in human and guinea-pig airways | journal = British Journal of Pharmacology | volume = 127 | issue = 2 | pages = 413–420 | date = May 1999 | pmid = 10385241 | pmc = 1566042 | doi = 10.1038/sj.bjp.0702573 }}</ref> thus inhibiting cholinergic transmission.

===Pharmacokinetics=== Glycopyrronium bromide affects the gastrointestinal tracts, liver and kidney but has a very limited effect on the brain and the central nervous system. In horse studies, after a single intravenous infusion, the observed tendencies of glycopyrronium followed a tri-exponential equation, by rapid disappearance from the blood followed by a prolonged terminal phase. Excretion was mainly in urine and in the form of an unchanged drug. Glycopyrronium has a relatively slow diffusion rate, and in a standard comparison to atropine, is more resistant to penetration through the blood-brain barrier and placenta.<ref>{{cite journal | vauthors = Rumpler MJ, Colahan P, Sams RA | title = The pharmacokinetics of glycopyrrolate in Standardbred horses | journal = Journal of Veterinary Pharmacology and Therapeutics | volume = 37 | issue = 3 | pages = 260–268 | date = June 2014 | pmid = 24325462 | doi = 10.1111/jvp.12085 }}</ref>

==Research== It has been studied in asthma.<ref name="pmid16236844">{{cite journal | vauthors = Hansel TT, Neighbour H, Erin EM, Tan AJ, Tennant RC, Maus JG, Barnes PJ | title = Glycopyrrolate causes prolonged bronchoprotection and bronchodilatation in patients with asthma | journal = Chest | volume = 128 | issue = 4 | pages = 1974–1979 | date = October 2005 | pmid = 16236844 | doi = 10.1378/chest.128.4.1974 | url = http://www.chestjournal.org/cgi/pmidlookup?view=long&pmid=16236844 | archive-url = https://archive.today/20130414111933/http://www.chestjournal.org/cgi/pmidlookup?view=long&pmid=16236844 | archive-date = 2013-04-14 | url-access = subscription }}</ref><ref name="pmid2225951">{{cite journal | vauthors = Gilman MJ, Meyer L, Carter J, Slovis C | title = Comparison of aerosolized glycopyrrolate and metaproterenol in acute asthma | journal = Chest | volume = 98 | issue = 5 | pages = 1095–1098 | date = November 1990 | pmid = 2225951 | doi = 10.1378/chest.98.5.1095 | url = http://www.chestjournal.org/cgi/pmidlookup?view=long&pmid=2225951 | archive-url = https://archive.today/20130414121303/http://www.chestjournal.org/cgi/pmidlookup?view=long&pmid=2225951 | archive-date = 2013-04-14 | url-access = subscription }}</ref>

== References == {{reflist}}

{{Drugs for functional gastrointestinal disorders}} {{Drugs for obstructive airway diseases}} {{Muscarinic acetylcholine receptor modulators}} {{Portal bar | Medicine}}

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