Glycopyrronium bromide

Glycopyrronium bromide is a medication of the muscarinic anticholinergic group. It does not cross the blood–brain barrier and consequently has few to no central effects. It is available in oral,[3] intravenous, topical,[4] and inhaled forms. It is a synthetic quaternary ammonium compound.[1]

Glycopyrronium bromide
Clinical data
Trade namesRobinul, Cuvposa, Seebri, others
Other namesglycopyrrolate (USAN US)
AHFS/Drugs.comMonograph
MedlinePlusa602014
License data
Pregnancy
category
  • AU: B2
Routes of
administration		By mouth, intravenous, inhalation, topical, injection, subcutaneous
ATC code
Legal status
Legal status
  • AU: S3 / S4
  • UK: POM (Prescription only)
  • US: ℞-only [1][2]
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Elimination half-life0.6–1.2 hours
Excretion85% Kidney, unknown amount in the bile
Identifiers
IUPAC name
  • 3-[2-Cyclopentyl(hydroxy)phenylacetoxy]-1,1-dimethylpyrrolidinium bromide
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.008.990
Chemical and physical data
FormulaC19H28BrNO3
Molar mass398.341 g·mol−1
3D model (JSmol)
SMILES
  • C[N+]1(CCC(C1)OC(=O)C(C2CCCC2)(C3=CC=CC=C3)O)C.[Br-]

  • as cation: C[N+]1(CCC(C1)OC(=O)C(C2CCCC2)(C3=CC=CC=C3)O)C
InChI
  • InChI=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
  • Key:VPNYRYCIDCJBOM-UHFFFAOYSA-M

  • as cation: InChI=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
  • Key:ANGKOCUUWGHLCE-UHFFFAOYSA-N
 NY (what is this?)  (verify)

The cation, which is the active moiety, is called glycopyrronium (INN)[5] or glycopyrrolate (USAN).

In June 2018, glycopyrronium was approved by the US Food and Drug Administration (FDA) to treat excessive underarm sweating, becoming the first drug developed specifically to reduce excessive sweating.[6] It is on the World Health Organization's List of Essential Medicines.[7]

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.[8] It is also used in conjunction with neostigmine, a neuromuscular blocking reversal agent, to prevent neostigmine's muscarinic effects such as bradycardia. It can be administered to raise the heart rate in bradycardia, which often will also increase the blood pressure.

It is also used to reduce excessive saliva (sialorrhea),[9][10][11] and Ménière's disease.[12]

It has been used topically and orally to treat hyperhidrosis, in particular, gustatory hyperhidrosis.[13][14]

In inhalable form it is used to treat chronic obstructive pulmonary disease (COPD).[15][16] Doses for inhalation are much lower than oral ones, so that swallowing a dose will not have an effect.[17][18]

In end-of-life care, this medication will often be administered to patients that become encumbered by their bronchial secretions and are no longer able to clear their own airway through insufficient coughing reflex.

Side effects

Dry mouth, urinary retention, headaches, vomiting, diarrhea, constipation, blurry vision are possible side effects of the medication.[8] Since glycopyrronium reduces the body's sweating ability, it can even cause hyperthermia and heat stroke in hot environments. The medication also induces drowsiness, an effect exacerbated by the consumption of alcohol.

Pharmacology

Mechanism of action

Glycopyrronium competitively blocks muscarinic receptors,[8][19] 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.[20]

Research

It has been studied in asthma.[21][22]

References
  1. "Robinul- glycopyrrolate tablet Robinul Forte- glycopyrrolate tablet". DailyMed. 1 June 2021. Retrieved 20 June 2022.
  2. "Dartisla ODT- glycopyrrolate orally disintegrating tablets tablet, orally disintegrating". DailyMed. 9 December 2021. Retrieved 20 June 2022.
  3. "Glycopyrrolate Oral Inhalation". MedlinePlus. Archived from the original on 17 August 2021. Retrieved 20 June 2022.
  4. "Glycopyrronium Topical". MedlinePlus. Archived from the original on 17 August 2021. Retrieved 20 June 2022.
  5. Bajaj V, Langtry JA (July 2007). "Use of oral glycopyrronium bromide in hyperhidrosis". Br. J. Dermatol. 157 (1): 118–21. doi:10.1111/j.1365-2133.2007.07884.x. PMID 17459043. S2CID 29080876.
  6. "FDA OKs first drug made to reduce excessive sweating". AP News. Archived from the original on 2018-07-02. Retrieved 2018-07-02.
  7. World Health Organization (2021). World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. hdl:10665/345533. WHO/MHP/HPS/EML/2021.02.
  8. Chabicovsky, Monika; Winkler, Swantje; Soeberdt, Michael; Kilic, Ana; Masur, Clarissa; Abels, Christoph (May 2019). "Pharmacology, toxicology and clinical safety of glycopyrrolate". Toxicology and Applied Pharmacology. 370: 154–169. doi:10.1016/j.taap.2019.03.016. PMID 30905688. S2CID 85498396.
  9. Mier RJ, Bachrach SJ, Lakin RC, Barker T, Childs J, Moran M (December 2000). "Treatment of sialorrhea with glycopyrrolate: A double-blind, dose-ranging study". Arch Pediatr Adolesc Med. 154 (12): 1214–8. doi:10.1001/archpedi.154.12.1214. PMID 11115305. Archived from the original on 2011-08-10. Retrieved 2008-11-26.
  10. Tscheng DZ (November 2002). "Sialorrhea - therapeutic drug options". Ann Pharmacother. 36 (11): 1785–90. doi:10.1345/aph.1C019. PMID 12398577. S2CID 45799443.
  11. Olsen AK, Sjøgren P (October 1999). "Oral glycopyrrolate alleviates drooling in a patient with tongue cancer". J Pain Symptom Manage. 18 (4): 300–2. doi:10.1016/S0885-3924(99)00080-9. PMID 10534970.
  12. Maria, Sammartano Azia; Claudia, Cassandro; Pamela, Giordano; Andrea, Canale; Roberto, Albera (1 December 2012). "Medical therapy in Ménière's disease". Audiological Medicine. 10 (4): 171–177. doi:10.3109/1651386X.2012.718413. S2CID 72380413.
  13. Kim WO, Kil HK, Yoon DM, Cho MJ (August 2003). "Treatment of compensatory gustatory hyperhidrosis with topical glycopyrrolate". Yonsei Med. J. 44 (4): 579–82. doi:10.3349/ymj.2003.44.4.579. PMID 12950111.
  14. Kim WO, Kil HK, Yoon KB, Yoon DM (May 2008). "Topical glycopyrrolate for patients with facial hyperhidrosis". Br. J. Dermatol. 158 (5): 1094–7. doi:10.1111/j.1365-2133.2008.08476.x. PMID 18294315. S2CID 39870296.
  15. "Seebri Breezhaler EPAR". European Medicines Agency (EMA). 17 September 2018. Archived from the original on 29 February 2020. Retrieved 28 February 2020.
  16. "Tovanor Breezhaler EPAR". European Medicines Agency (EMA). 17 September 2018. Archived from the original on 29 February 2020. Retrieved 28 February 2020.
  17. "EPAR – Product information for Seebri Breezhaler" (PDF). European Medicines Agency. 28 September 2012. Archived (PDF) from the original on 30 July 2018. Retrieved 4 February 2017.
  18. Tzelepis G, Komanapolli S, Tyler D, Vega D, Fulambarker A (January 1996). "Comparison of nebulized glycopyrrolate and metaproterenol in chronic obstructive pulmonary disease". Eur. Respir. J. 9 (1): 100–3. doi:10.1183/09031936.96.09010100. PMID 8834341.
  19. Haddad EB, Patel H, Keeling JE, Yacoub MH, Barnes PJ, Belvisi MG (May 1999). "Pharmacological characterization of the muscarinic receptor antagonist, glycopyrrolate, in human and guinea-pig airways". Br. J. Pharmacol. 127 (2): 413–20. doi:10.1038/sj.bjp.0702573. PMC 1566042. PMID 10385241.
  20. Rumpler, M.J.; Colahan, P.; Sams, R.A. (2014). "The pharmacokinetics of glycopyrrolate in Standardbred horses". Journal of Veterinary Pharmacology and Therapeutics. 37 (3): 260–8. doi:10.1111/jvp.12085. PMID 24325462.
  21. Hansel TT, Neighbour H, Erin EM, et al. (October 2005). "Glycopyrrolate causes prolonged bronchoprotection and bronchodilatation in patients with asthma". Chest. 128 (4): 1974–9. doi:10.1378/chest.128.4.1974. PMID 16236844. Archived from the original on 2013-04-14.
  22. Gilman MJ, Meyer L, Carter J, Slovis C (November 1990). "Comparison of aerosolized glycopyrrolate and metaproterenol in acute asthma". Chest. 98 (5): 1095–8. doi:10.1378/chest.98.5.1095. PMID 2225951. Archived from the original on 2013-04-14.
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