Glucagon (medication)

verifiedfields	changed
watchedfields	changed
verifiedrevid	461121086
drug name	Glucagon
tradename	Glucagen, Baqsimi, Gvoke, others
medlineplus	a682480
dailymedid	Glucagon
pregnancy au	B3
pregnancy au comment	‡R1R‡
routes of administration	Intranasal, intravenous (IV), intramuscular (IM), subcutaneous
atc prefix	H04
atc suffix	AA01
legal ca comment	Ethical‡R2R‡
legal uk	POM
legal uk comment	‡R3R‡
legal us	Rx-only
legal us comment	‡R4R‡‡R5R‡
legal eu	Rx-only
legal eu comment	‡R6R‡‡R7R‡
legal status	Rx-only
cas number	16941-32-5
pubchem	16132283
iuphar ligand	1136
drugbank	DB00040
chemspiderid	17288942
unii	76LA80IG2G
kegg	D00116
kegg2	C01501
chebi	5391
chembl	266481
iupac name	Glucagon
c	153
h	225
n	43
o	49
s	1
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Glucagon, sold under the brand name Baqsimi among others, is a medication and hormone.[8] As a medication it is used to treat low blood sugar, beta blocker overdose, calcium channel blocker overdose, and those with anaphylaxis who do not improve with epinephrine. It is given by injection into a vein, muscle, or under the skin. A version given in the nose is also available.

Common side effects include vomiting. Other side effects include low blood potassium and low blood pressure.[8] It is not recommended in people who have a pheochromocytoma or insulinoma. Use in pregnancy has not been found to be harmful to the baby.[9] Glucagon is in the glycogenolytic family of medications.[10]

Medical uses

Low blood sugar

An injectable form of glucagon may be part of first aid in cases of low blood sugar when the person is unconscious or for other reasons cannot take glucose orally or by intravenous.[13] The glucagon is given by intramuscular, intravenous or subcutaneous injection, and quickly raises 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 beta blockers; the likely mechanism of action is the increase of cAMP in the myocardium, in effect bypassing the β-adrenergic second messenger system.[14]

Anaphylaxis

Some people who have anaphylaxis and are on beta blockers are resistant to epinephrine.<!-- [15]

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").[16] There is little evidence for glucagon's effectiveness in this condition,[17][18] and glucagon may induce nausea and vomiting,[19] 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.[20][21]

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.[22]

Mechanism of action

Glucagon binds to the glucagon receptor, a G protein-coupled receptor, located in the plasma membrane. The conformation change in the receptor activates G proteins, a heterotrimeric protein with α, β, and γ subunits. When the G protein interacts with the receptor, it undergoes a conformational change that results in the replacement of the GDP molecule that was bound to the α subunit with a GTP molecule. This substitution results in the releasing of the α subunit from the β and γ subunits. The alpha subunit specifically activates the next enzyme in the cascade, adenylate cyclase.

Adenylate cyclase manufactures cyclic adenosine monophosphate (cyclic AMP or cAMP), which activates protein kinase A (cAMP-dependent protein kinase). This enzyme, in turn, activates phosphorylase kinase, which then phosphorylates glycogen phosphorylase b, converting it into the active form called phosphorylase a. Phosphorylase a is the enzyme responsible for the release of 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]

References

Glucagon Use During Pregnancy Drugs.com, 16 October 2019, retrieved 16 May 2020^

Baqsimi Product information Health Canada, retrieved 2024-03-30^

GlucaGen Hypokit 1 mg - Summary of Product Characteristics (SmPC) (emc), 15 June 2015, retrieved 16 May 2020^

Glucagon kit DailyMed, retrieved 27 February 2021^

Baqsimi- glucagon powder DailyMed, retrieved 27 February 2021^

Baqsimi EPAR European Medicines Agency, 17 October 2019, retrieved 27 February 2021^

Ogluo Product information Union Register of medicinal products, retrieved 3 March 2023^

British national formulary : BNF 69 British Medical Association, 2015^

Glucagon (GlucaGen) Use During Pregnancy www.drugs.com, retrieved 27 December 2016^

Glucagon The American Society of Health-System Pharmacists, retrieved 8 December 2016^

World Health Organization model list of essential medicines: 21st list 2019 World Health Organization, 2019^

FDA Approves First Generic of Drug Used to Treat Severe Hypoglycemia U.S. Food and Drug Administration (FDA), 28 December 2020, retrieved 28 December 2020^

CDC. Treatment of Low Blood Sugar (Hypoglycemia) Diabetes, 2024-06-05, retrieved 2024-07-27^

A review of potential cardiovascular uses of intravenous glucagon administration Journal of Clinical Pharmacology, May 1999^

--> In this situation glucagon intravenously may be useful to treat their low blood pressure.<ref name=Tang2003> A practical guide to anaphylaxis American Family Physician, October 2003^

Review of food bolus management Canadian Journal of Gastroenterology, October 2008^

Myth: glucagon is an effective first-line therapy for esophageal foreign body impaction CJEM, March 2009^

The management of oesophageal soft food bolus obstruction: a systematic review Annals of the Royal College of Surgeons of England, September 2011^

Safety and efficacy of glucagon for the relief of acute esophageal food impaction American Journal of Health-System Pharmacy, April 2012^

Management of ingested foreign bodies and food impactions Gastrointestinal Endoscopy, June 2011^

Management and endoscopic techniques for digestive foreign body and food bolus impaction Digestive and Liver Disease, July 2013^

Clinical safety and outcomes of glucagon use during endoscopic retrograde cholangiopancreatography (ERCP) Endoscopy International Open, April 2022^

Potentiation by glucagon of the hypoprothrombinemic action of warfarin Annals of Internal Medicine, March 1970^

Endotext MDText.com, Inc., 2000, retrieved 6 April 2022^

Role of fructose 2,6-bisphosphate in the control of glycolysis in mammalian tissues The Biochemical Journal, July 1987^

The role of fructose 2,6-bisphosphate in the regulation of carbohydrate metabolism Current Topics in Cellular Regulation, 1984^

Hormonal control of pyruvate kinase activity and of gluconeogenesis in isolated hepatocytes Proceedings of the National Academy of Sciences of the United States of America, August 1976^

Aqueous extracts of pancreas III. Some precipitation reactions of insulin J. Biol. Chem., 1923^

The amino acid sequence of glucagon V. Location of amide groups, acid degradation studies and summary of sequential evidence J. Am. Chem. Soc., 1957^

FDA approves first treatment for severe hypoglycemia that can be administered without an injection U.S. Food and Drug Administration (FDA), 24 July 2019, retrieved 16 May 2020^

Drug Approval Package: Baqsimi U.S. Food and Drug Administration (FDA), 25 November 2019, retrieved 17 May 2020^

Ready for rescue: new nasally administered glucagon for severe hypoglycemia approved in Canada! Diabetes Canada, 12 December 2019, retrieved 16 May 2020^

GLUCAGON NASAL POWDER (BAQSIMI — ELI LILLY CANADA INC) CADTH, 22 January 2020, retrieved 16 May 2020^

glucagon CADTH.ca, 25 June 2019, retrieved 17 May 2020^

Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. Ogluo: Pending EC decision European Medicines Agency (EMA), 10 December 2020, retrieved 11 December 2020^

Ogluo EPAR European Medicines Agency (EMA), 9 December 2020, retrieved 27 February 2021^

Glucagon (medication)

Medical uses

Low blood sugar

Beta blocker overdose

Anaphylaxis

Impacted food bolus

Endoscopic retrograde cholangiopancreatography

Adverse effects

Contraindications

Mechanism of action

History

External links

References