Mechanism of effect
Glucagon binds the glucagon receptor, a G protein-coupled receptor located in the plasma membrane, which then initiates a dual signaling pathway using both adenylate cyclase activation and increased intracellular calcium. Adenylate cyclase manufactures cAMP (cyclic AMP), which activates protein kinase A (cAMP-dependent protein kinase).
This enzyme, in turn, activates phosphorylase kinase, which, in turn, phosphorylates glycogen phosphorylase, converting into the active form called phosphorylase A. Phosphorylase A is the enzyme responsible for the release of glucose-1-phosphate from glycogen polymers. This yields glucose molecules to be released into the blood. Glucagon receptors are found in the liver, kidney, brain and pancreatic islet cells. The glucagon mediated signals lead to an increase in insulin excretion
Pharmacodynamic
Used in the treatment of hypoglycemia and in gastric imaging, glucagon increases blood glucose concentration and is used in the treatment of hypoglycemia. Glucagon acts only on liver glycogen, converting it to glucose through the release of insulin. It also relaxes the smooth muscles of the gastrointestinal tract.
Pharmacokinetics
Half-Life: 8-18 min IV; 45 min IM (apparent)
Peak Plasma Time: 13 min IM; 20 min SC
Bioavailability: IM: 30%
Vd: 0.2-0.25 L/kg
Metabolism: by blood, liver, & kidney
Onset
- Increase in glucose levels: 5-20 min IV; 30 min IM; 30-45 min SC
- Diagnostic effect: 1 min IV; 4-10 min IM
Duration
- Increase in glucose levels: 60-90 min (IV/IM/SC)
- GI relaxation: 9-25 min IV; 12-32 min IM
Clearance
- Renal: 19-21 mL/kg/min
- Total Body: 135 mL/min/kg
Dosage
Adult
Hypoglycemia
1 mg (1 unit) IM/SC/IV if no IV for dextrose
Repeat q15min once or twice; give dextrose as soon as it is available and if no response
Administer supplemental carbohydrate to replete glycogen stores
Radiography of GI
To inhibit motility of stomach and small bowel: 0.2-0.5 mg IV over time period of 1 min or 1 mg IM
To inhibit motility of colon: 0.5-0.75 mg IV over time period of 1 min or 1 mg IM
Bolus doses >1 mg administered IV may cause nausea and vomiting and are not recommended
Pediatric
Hypoglycemia
Administer oral glucose/IVdextrose to replete glycogen stores
GlucaGen
- <6 years: 0.5 mg SC/IM/IV; may repeat in 15 min if necessary
- >6 years: 1 mg SC/IM/IV; may repeat in 15 min if necessary
- Alternatively,
- <25 kg: 0.5 mg; may repeat in 15 min if necessary
- ≥25 kg: 1 mg; may repeat in 15 min if necessary
Glucagon Emergency Kit
- <20 kg: 0.5 mg SC/IM/IV q15min PRN, OR 0.02-0.03 mg/kg/dose SC/IM/IV; may repeat in 15 min if necessary
- ≥20 kg: 1 mg SC/IM/IV; may repeat in 15 min if necessary q20min PRN
Drug contraindications
HypersensitivityInteractions
Aclidinium , Phenindione , Enoxaparin , Indomethacin , Protamine sulfat , Heparin , Warfarin , Bivalirudin , Argatroban , Lepirudin , Dalteparin , Tinzaparin , Antithrombin alfa , fondaparinux , dichlorphenamide , UmeclidiniumAlerts
Generalized allergic reactions, including urticaria, respiratory distress, and hypotension reported; if symptoms occur discontinue and treat as indicated
Effective in treating hypoglycemia only if sufficient liver glycogen present
Because glucagon is of little or no help in states of starvation, adrenal insufficiency, or chronic hypoglycemia, hypoglycemia in these conditions should be treated with glucose
Increased blood pressure and heart rate in patients with cardiac disease reported; monitor patients with known cardiac disease
Awaken patient following administration to provide oral glucose if possible, otherwise IV dextrose is required to replete glycogen stores
Points of recommendation
Call your doctor after each time you use a glucagon injection.
Hypoglycemia should be treated as quickly as possible. Having low blood sugar for too long can cause seizure, coma, or death.
Glucagon is a powder medicine that must be mixed with a liquid (diluent) before using it. Prepare a dose only when you are ready to give an injection. Do not use if the medicine has changed colors or has particles in it. Mix a new dose, and call your doctor for instructions if the second dose also has particles after mixing.
Be sure you know how to give a glucagon injection before you need to use it. Use half of the adult dose if you are giving an injection to a child younger than 6, or to anyone who weighs less than 55 pounds.
After the injection, you should eat a fast-acting source of sugar (fruit juice, glucose gel, hard candy, raisins, or non-diet soda) and then eat a snack or small meal such as cheese and crackers or a meat sandwich.
Low blood sugar (hypoglycemia) can happen to everyone who has diabetes. Symptoms include headache, hunger, sweating, irritability, dizziness, nausea, fast heart rate, and feeling anxious or shaky. To quickly treat low blood sugar, always keep a fast-acting source of sugar with you such as fruit juice, hard candy, crackers, raisins, or non-diet soda.
Blood sugar levels can be affected by stress, illness, surgery, exercise, alcohol use, or skipping meals. Ask your doctor before changing your dose or medication schedule.
To keep from having severe hypoglycemia, follow your diet, medication, and exercise routines very closely.
Store glucagon powder and the diluent at cool room temperature away from moisture, heat, and light. Throw away any mixed medicine you have not used right away.
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