Glucagon (medication)

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Baqsimi
)
This article is about the medication. For the natural hormone, see Glucagon.

Glucagon
amino terminus below
Clinical data
Trade namesGlucagen, Baqsimi, Gvoke, others
AHFS/Drugs.comMonograph
MedlinePlusa682480
License data
Pregnancy
category
subcutaneous injection
ATC code
Legal status
Legal status
Identifiers
  • Glucagon
JSmol)
  • C[C@H]([C@@H](C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](Cc2ccc(cc2)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc3ccc(cc3)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](Cc4ccccc4)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](Cc5c[nH]c6c5cccc6)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H]([C@@H](C)O)C(=O)O)NC(=O)CNC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CO)NC(=O)[C@H](Cc7cnc[nH]7)N)O
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Glucagon, sold under the brand name Baqsimi among others, is a

under the skin.[10] A version given in the nose is also available.[11]

Common side effects include vomiting.

glycogenolytic family of medications.[10] It works by causing the liver to break down glycogen into glucose.[10]

Glucagon was approved for medical use in the United States in 1960.[10] It is on the World Health Organization's List of Essential Medicines.[13] It is a manufactured form of the glucagon hormone.[10] A generic version became available in the United States in December 2020.[14]

Medical uses

Low blood sugar

An injectable form of glucagon may be part of first aid in cases of

blood glucose
levels. To use the injectable form, it must be reconstituted prior to use, a step that requires a sterile diluent to be injected into a vial containing powdered glucagon, because the hormone is highly unstable when dissolved in solution. When dissolved in a fluid state, glucagon can form amyloid fibrils, or tightly woven chains of proteins made up of the individual glucagon peptides, and once glucagon begins to fibrilize, it becomes useless when injected, as the glucagon cannot be absorbed and used by the body. The reconstitution process makes using glucagon cumbersome, although there are a number of products now in development from a number of companies that aim to make the product easier to use.

Beta blocker overdose

Anecdotal evidence suggests a benefit of higher doses of glucagon in the treatment of overdose with

myocardium, in effect bypassing the β-adrenergic second messenger system.[15]

Anaphylaxis

Some people who have

epinephrine. In this situation glucagon intravenously may be useful to treat their low blood pressure.[16]

Impacted food bolus

Glucagon relaxes the

lower esophageal sphincter and may be used in those with an impacted food bolus in the esophagus ("steakhouse syndrome").[17] There is little evidence for glucagon's effectiveness in this condition,[18][19][20] and glucagon may induce nausea and vomiting,[20] but considering the safety of glucagon this is still considered an acceptable option as long it does not lead to delays in arranging other treatments.[21][22]

Endoscopic retrograde cholangiopancreatography

Glucagon's effect of increasing cAMP causes relaxation of splanchnic smooth muscle, allowing

cannulation of the duodenum during the endoscopic retrograde cholangiopancreatography
(ERCP) procedure.

Adverse effects

Glucagon acts very quickly; common side-effects include headache and nausea.

Drug interactions: Glucagon interacts only with oral anticoagulants, increasing the tendency to bleed.[23]

Contraindications

While glucagon can be used clinically to treat various forms of hypoglycemia, it is contraindicated in patients with

hypoglycemia.[4]

Mechanism of action

Metabolic regulation of glycogen by glucagon.

Glucagon binds to the

adenylate cyclase.[24]

Adenylate cyclase manufactures

glucose-1-phosphate from glycogen polymers.[24]

Additionally, the coordinated control of glycolysis and gluconeogenesis in the liver is adjusted by the phosphorylation state of the enzymes that catalyze the formation of a potent activator of glycolysis called fructose-2,6-bisphosphate.[25] The enzyme protein kinase A that was stimulated by the cascade initiated by glucagon will also phosphorylate a single serine residue of the bifunctional polypeptide chain containing both the enzymes fructose-2,6-bisphosphatase and phosphofructokinase-2. This covalent phosphorylation initiated by glucagon activates the former and inhibits the latter. This regulates the reaction catalyzing fructose-2,6-bisphosphate (a potent activator of phosphofructokinase-1, the enzyme that is the primary regulatory step of glycolysis)[26] by slowing the rate of its formation, thereby inhibiting the flux of the glycolysis pathway and allowing gluconeogenesis to predominate. This process is reversible in the absence of glucagon (and thus, the presence of insulin).

Glucagon stimulation of PKA also inactivates the glycolytic enzyme pyruvate kinase.[27]

History

In the 1920s, Kimball and Murlin studied pancreatic extracts, and found an additional substance with hyperglycemic properties. They described glucagon in 1923.[28] The amino acid sequence of glucagon was described in the late 1950s.[29] A more complete understanding of its role in physiology and disease was not established until the 1970s, when a specific radioimmunoassay was developed.

A nasal version was approved for use in the United States and Canada in 2019.[11][30][31][32][33]

On 10 December 2020, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Ogluo, intended for the treatment of severe hypoglycemia in diabetes mellitus.[34] The applicant for this medicinal product is Xeris Pharmaceuticals Ireland Limited. It was approved for medical use in the European Union in February 2021.[7]

References

  1. ^ "Glucagon Use During Pregnancy". Drugs.com. 16 October 2019. Retrieved 16 May 2020.
  2. ^ "Baqsimi Product information". Health Canada. Retrieved 30 March 2024.
  3. ^ "GlucaGen Hypokit 1 mg - Summary of Product Characteristics (SmPC)". (emc). 15 June 2015. Retrieved 16 May 2020.
  4. ^ a b c "Glucagon kit". DailyMed. Retrieved 27 February 2021.
  5. ^ "Baqsimi- glucagon powder". DailyMed. Retrieved 27 February 2021.
  6. ^ "Baqsimi EPAR". European Medicines Agency. 17 October 2019. Retrieved 27 February 2021.
  7. ^ a b "Ogluo EPAR". European Medicines Agency (EMA). 9 December 2020. Retrieved 27 February 2021.
  8. ^ "Ogluo Product information". Union Register of medicinal products. Retrieved 3 March 2023.
  9. ^
    ISBN 9780857111562
    .
  10. ^ a b c d e f g h "Glucagon". The American Society of Health-System Pharmacists. Archived from the original on 26 December 2016. Retrieved 8 December 2016.
  11. ^ a b "FDA approves first treatment for severe hypoglycemia that can be administered without an injection". U.S. Food and Drug Administration (FDA) (Press release). 24 July 2019. Retrieved 16 May 2020.
  12. ^ "Glucagon (GlucaGen) Use During Pregnancy". www.drugs.com. Archived from the original on 27 December 2016. Retrieved 27 December 2016.
  13. hdl:10665/325771
    . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  14. ^ "FDA Approves First Generic of Drug Used to Treat Severe Hypoglycemia". U.S. Food and Drug Administration (FDA) (Press release). 28 December 2020. Retrieved 28 December 2020.
  15. S2CID 34512730
    .
  16. PMID 14567487
    .
  17. PMID 18925301
    .
  18. PMID 19272219
    .
  19. PMID 21929913
    .
  20. ^
    PMID 22441787
    .
  21. PMID 21628009. Archived
    (PDF) from the original on 8 August 2013.
  22. PMID 23266207
    .
  23. PMID 5415418
    .
  24. ^
    PMID 25905350
    . Retrieved 6 April 2022.
  25. PMID 2822019
    .
  26. PMID 6327193
    .
  27. PMID 183209
    .
  28. doi:10.1016/S0021-9258(18)85474-6. Archived
    from the original on 29 September 2007.
  29. doi:10.1021/ja01568a038
    .
  30. ^ "Drug Approval Package: Baqsimi". U.S. Food and Drug Administration (FDA). 25 November 2019. Retrieved 17 May 2020.
  31. ^ "Ready for rescue: new nasally administered glucagon for severe hypoglycemia approved in Canada!". Diabetes Canada. 12 December 2019. Retrieved 16 May 2020.
  32. ^ "GLUCAGON NASAL POWDER (BAQSIMI — ELI LILLY CANADA INC)" (PDF). CADTH. 22 January 2020. Retrieved 16 May 2020.
  33. ^ "glucagon". CADTH.ca. 25 June 2019. Retrieved 17 May 2020.
  34. ^ "Ogluo: Pending EC decision". European Medicines Agency (EMA). 10 December 2020. Archived from the original on 1 January 2021. Retrieved 11 December 2020. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.

External links

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