Glycopyrronium bromide

from Wikipedia, the free encyclopedia
Structural formula
Structure of the Br - ion     Structural formula of glycopyrronium bromide
Simplified structural formula - complex mixture of stereoisomers
General
Non-proprietary name Glycopyrronium bromide
other names
  • (±) - ( R * ) -3 - [( S * ) -2-Cyclopentyl-2-hydroxy-2-phenylacetoxy] -1,1-dimethylpyrrolidinium bromide ( IUPAC )
  • Glycopyrrolate ( USAN )
Molecular formula C 19 H 28 BrNO 3
External identifiers / databases
CAS number 596-51-0
EC number 209-887-0
ECHA InfoCard 100.008.990
PubChem 11693
ChemSpider 11201
Wikidata Q27162963
Drug information
ATC code

A03 AB02

Drug class

Anticholinergics

properties
Molar mass 398.34 g · mol -1
Physical state

firmly

Melting point

193.2-194.5 ° C

safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances
07 - Warning

Caution

H and P phrases H: 315-319-335
P: ?
Toxicological data

709 mg kg −1 ( LD 50 ,  rat ,  oral )

As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Glycopyrronium bromide is a drug from the group of parasympatholytics . The cation of the substance is called glycopyrronium (according to INN ) or glycopyrrolate (according to USAN ).

Clinical information

Application areas (indications)

Adverse effects (side effects)

The peripheral anticholinergic effects include, in particular, constipation , decreased sweating, and dryness of the mouth, nose and throat. Irritation or inflammation can occur at the application site.

Pharmacological properties

Mechanism of action (pharmacodynamics)

Glycopyrronium bromide competitively inhibits the effects of acetylcholine on muscarinic cholinergic neurons ( postganglionic ). So it is a competitive antagonism of muscarinic receptors (M-cholino receptors ). Such peripheral cholinergic receptors are located in the autonomic effector cells of the smooth muscles, the heart muscle, the sinus node, the atrioventricular node, the exocrine glands and, to a limited extent, in the autonomic ganglia. Excessive secretion production is restricted in the pharynx, trachea and bronchi. The muscarinic receptors in the salivary glands respond strongly to anticholinergics . An inhibition of the saliva secretion already occurs at a dosage at which other undesirable anticholinergic effects do not occur, i.e. That is, the likelihood of side effects occurring with this indication is lower. A reduction in the increased flow of saliva often leads to an improvement in the ability to speak.

Absorption and distribution in the body (pharmacokinetics)

Glycopyrronium is a synthetic, ionized (low fat solubility), quaternary ammonium anticholinergic that does not pass through cell membranes. Accordingly, glycopyrronium bromide penetrates the CNS or the eye tissue with difficulty. Side effects such as sedation or delirium are therefore rarely found ( blood-brain barrier ). Oral absorption is poor, the potency ratio of IV injection to oral is about 35: 1. Nevertheless, 200–400 µg glycopyrronium p. o. three times a day at plasma concentrations that inhibit saliva secretion for up to 7 hours. When administered intravenously, glycopyrronium is two to five times more potent than scopolamine hydrobromide for inhibiting secretion . Therefore it can lead to inhibition of secretion in some patients who do not respond to scopolamine . However, the effectiveness of scopolamine hydrobromide, butylscopolamine bromide and glycopyrronium as anti-secretion agents is generally comparable. Terminal rattle breathing is relieved in one-third to one-half of patients. The optimal single parenteral dose is 200 µg. Compared to scopolamine hydrobromide, the onset of action of glycopyrronium is slower. It has fewer cardiac side effects due to its lower affinity for type 2 muscarinic receptors. Although glycopyrronium does not change the intraocular pressure or pupil size in standard doses, it can promote narrow-angle glaucoma . The elimination is via the kidneys. Therefore, even lower doses are effective in patients with renal insufficiency.

preparations

  • Monopreparation for injection: Robinul
  • Inhalation monopreparation: Seebri ( Breezhaler )
  • Combination preparation with indacaterol for inhalation: Ultibro
  • Combination preparation with beclometasone and formoterol for inhalation: Trimbow

Individual evidence

  1. ↑ a b entry on glycopyrronium bromide. In: Römpp Online . Georg Thieme Verlag, accessed on November 10, 2014.
  2. ↑ Template: CL Inventory / not harmonized There is not yet a harmonized classification for this substance . A labeling of Glycopyrronium bromide in the Classification and Labeling Inventory of the European Chemicals Agency (ECHA), retrieved on May 26, 2020, is reproduced from a self-classification by the distributor .
  3. ^ A b c Robert Twycross, Andrew Wilcock, Claudia Bausewein and Constanze Rémi: Drug therapy in palliative medicine. , (2005) 293-295.
  4. ↑ a b AIi-Melkkila T et al .: Pharmacokinetics and related pharmacodynamics of anticholinergic drugs. , Acta Anaesthesiologica Scandinavica 37 (1993) 633-642.
  5. ↑ Rashid H et al .: Management of secretions in esophageal cancer patients with glycopyrrolate. , Annals of Oncology 8 (1997) 198-199.
  6. ↑ a b Mirakhur Rand, Dundee J: Glycopyrrolate pharmacology and clinical use. , Anaesthesia 38 (1983) 1195-1204.
  7. ↑ Gram D et al .: Central anticholinergic syndrome following glycopyrrolate. , Anesthesiology 74 (1991) 191-193.
  8. ^ Wigard D: Glycopyrrolate and the central anticholinergic syndrome (letter). , Anesthesiology 75 (1991) 1125.
  9. ↑ a b Mirakhur Rand, Dundee J: A comparison of the effects of atropine and glycopyrrolate on various end organs. , Journal of the Royal Society of Medicine 73 (1980) 727-730.
  10. ↑ Ali-Melkkila T et al .: Glycopyrrolate; pharmacokinetics and some pharmacodynamics findings. , Acta Anesthesiologica Scandinavica 33 (1989) 513-517.
  11. ↑ Blasco P: Glycopyrrolate treatment of chronic drooling. , Archives of Pediatric and Adolescent Medicine 150 (1996) 932-935.
  12. ↑ Olsen A and Sjogren P: Oral glycopyrrolate alleviates drooling in a patient with tongue cancer. , Journal of Pain and Symptom Management 18 (1999) 300-302.
  13. ^ Hughes A et al .: Audit of three antimuscarinic drugs for managing retained secretions. , Palliative Medicine 14 (2000) 221-222.
  14. ↑ Mirakhur R et al .: Evaluation of the anticholinergic actions of glycopyrronium bromide. , British Journal of Clinical Pharmacology 5 (1978) 77-84.
  15. ↑ Back I et al .: Medicinal A study comparing hyoscine hydrobromide and glycopyrrolate in the treatment of death rattle. , Palliative Medicine 15 (2001) 329-336.
  16. ↑ Mirakhur R et al .: Atropine and glycopyrronium premedication. A comparison of the effects on cardiac rate and rhythm during induction of anesthesia. In: Anaesthesia . 1978; 33: 906-912.
  17. ↑ Warren J et al .: Effect of autonomic blockade on power spectrum of heart rate variability during exercise. In: American Journal of Physiology-Regulatory, Integrative and Comparative Physiology . 1997; 273: 495-502.
  18. ↑ Scheinin H et al .: Spectral analysis of heart rate variability as a quantitative measure of parasympatholytic effect - integrated pharmacokinetics and pharmacodynamics of three anticholinergic drugs. In: Therapeutic Drug Monitoring . 1999; 21: 141-151.