GLUCAGON

HYPOGLYCEMIA - Glucagon is used in the treatment of severe hypoglycemia in patients with adequate liver glycogen stores (Prod Info glucagon injection, 2005). Glucagon kits are available for emergency use and contain 1 vial containing 1 mg of glucagon {rDNA origin} for injection with a disposable syringe containing 1 mL of sterile water for reconstitution (Prod Info GLUCAGEN(R) HYPOKIT injection, 2004; Prod Info GLUCAGEN(R) HYPOKIT injection, 2004). It should be administered either by the intramuscular or subcutaneous route to patients that are unconscious or unable to swallow. Once the patient regains consciousness, an oral carbohydrate should be given to prevent secondary hypoglycemia and to partly restore potentially depleted hepatic glycogen stores. If no response to glucagon, seek medical help immediately (Pearson, 2008).
ANTIDOTE (BETA-ADRENERGIC and CALCIUM CHANNEL BLOCKERS) - Glucagon has been used in the treatment of beta blocker and calcium channel blocker overdose (Lee, 2004; Bailey, 2003; Papadopoulos & O'Neil, 2000). It has cardiac inotropic and chronotropic effects. There is also in vitro evidence that glucagon decreases conduction time (Seger, 2006).
In cases of symptomatic bradycardia and hypotension following a beta-blocker overdose, high-dose glucagon is considered first-line antidote therapy (Shepherd, 2006). The clinical effects following a calcium channel blocker overdose can be similar to a beta-adrenergic antagonist overdose, which can include hypotension, bradycardia, heart block, and myocardial depression. Animal studies have shown that glucagon can reverse the myocardial depression that is observed with nifedipine, diltiazem and verapamil toxicity (Howland, 2006).

CALCIUM CHANNEL BLOCKER - A 59-year-old man took a "handful" of 30-mg extended-release tablets and was admitted with hypotension. Despite pharmacologic support, blood pressure ranged from 55/40 to 77/53 mmHg. The patient was given 1 mg of glucagon IV every 3 minutes for a total of 4 doses; blood pressure increased to 127/78 mmHg and the patient became more alert. A glucagon drip was started and maintained for approximately 17 hours when the patient was weaned from norepinephrine. The patient completely recovered (Papadopoulos & O'Neil, 2000).

TRICYCLIC ANTIDEPRESSANTS (TCA) - TCAs, sodium channel blocking agents, can produce cardiotoxicity. In case reports of TCA cardiotoxicity, use of glucagon has been associated with improved hemodynamic function when used in conjunction with multiple other agents. It has been shown that glucagon improves action potential, which suggests that it can increase the movement of sodium ions into the cardiac cell and decrease conduction time (Seger, 2006; Sensky & Olczak, 1999).

CASE REPORT - A 36-year-old woman developed profound hypotension (persistent systolic hypotension of 50-60 mmHg), cardiac dysrhythmias, and seizures following a dothiepin overdose. Although the patient was receiving several inotropic agents, the administration of a 10 mg bolus of glucagon improved blood pressure to 90 mmHg. Several further doses of glucagon were given and the patient recovered fully by day 5. Heart rate was stable after the second dose of glucagon (Sensky & Olczak, 1999). The authors concluded that glucagon significantly contributed to the hemodynamic stabilization and improvement of this patient.

DIAGNOSTIC AID - Parenteral administration of glucagon can relax smooth muscle and diminish intestinal motility, therefore; it is useful in the radiologic examination of the stomach, duodenum, small bowel, and colon (Prod Info glucagon injection, 2005).(Maglinte & Chernish, 1992).
COMATOSE PATIENTS/NOT RECOMMENDED - Glucagon had been recommended in the past as an initial treatment for all comatose patients to treat suspected hypoglycemia; its use is NO longer recommended. Two disadvantages of its use: (1) a patient must have adequate glycogen stores, and (2) it takes time for it to act. Intravenous dextrose (0.5 to 1.0 g/kg of 50% dextrose) is the preferred agent to give to all patients that present with an altered mental status thought to be related to hypoglycemia. Glucagon can have a role in treating hypoglycemia in the home (ie, prepared Glucagon kits) when intravenous dextrose is not available. In patients with insulinoma, glucagon can produce a rebound hypoglycemia following a temporary rise in blood sugar (Howland, 2006).

FORMS

Glucagon Emergency Kit - Glucagon 1 mg (1 unit) with 1 mL of sterile water for reconstitution in a disposable syringe (Prod Info glucagon injection, 2005; Prod Info GLUCAGEN(R) HYPOKIT injection, 2004).

-CLINICAL EFFECTS

GENERAL CLINICAL EFFECTS

USES: Glucagon is indicated for the treatment of severe hypoglycemia, and to treat beta blocker overdose and less commonly calcium channel blocker overdose. It may also be used as a diagnostic aid and to treat esophageal foreign bodies.

PHARMACOLOGY: Glucagon induces liver glycogen breakdown, releasing glucose from the liver. Hepatic stores of glycogen are needed for glucagon to produce an antihypoglycemic effect. Binding of glucagon to receptors on the heart stimulates conversion of DTP to cyclic AMP, which increases heart rate and strength of contraction.

EPIDEMIOLOGY: Overdose is uncommon.

WITH POISONING/EXPOSURE

MILD TO MODERATE TOXICITY: Symptoms of nausea, vomiting, gastric hypotonicity and diarrhea would be expected following overdose. Toxicity is anticipated to be an extension of adverse events reported and may include: hyperglycemia or hypoglycemia, hypokalemia, and an increase in blood pressure.
SEVERE TOXICITY: Based on its short half-life, significant protracted overdose effects are not expected to develop.

WITH THERAPEUTIC USE

ADVERSE EFFECTS: Nausea and vomiting may be expected. Severe reactions are not anticipated. Reactive hypoglycemia can develop following the administration of glucagon. Hypokalemia may also occur. Acute allergic reactions (including urticaria, respiratory distress, and hypotension) have been reported rarely following intravenous administration.

Editor's Note: An ERG guide with information appropriate to this material does not exist.

-FIRST AID

FIRST AID AND PREHOSPITAL TREATMENT

Decontamination is not necessary. Glucagon is administered parenterally, and can be a potent emetic. Following inadvertent ingestion, decontamination is not indicated because glucagon, a polypeptide, is rapidly destroyed in the gastrointestinal tract.

Consider activated charcoal only if a mixed ingestion is suspected; protect airway as necessary.

-RANGE OF TOXICITY

MINIMUM LETHAL EXPOSURE

A minimum lethal dose in humans has not been established.

ANIMAL DATA: In mice and rats, the median lethal intravenous dose is approximately 300 mg/kg and 38.6 mg/kg, respectively (Prod Info glucagon injection, 2005).

MAXIMUM TOLERATED EXPOSURE

A maximum tolerated dose in humans has not been established.

ANTIDOTE FOR CARDIAC TOXICITY: Glucagon is a first-line antidotal therapy for beta-blocker overdose (Shepherd, 2006). An initial bolus of 50 to 150 mcg/kg (usually about 10 mg in an adult) over 1 minute; followed by a continuous IV infusion of 50 to 100 mcg/kg/hr (DeWitt & Waksman, 2004).

Carcinogenicity Ratings for CAS16941-32-5 :

ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
EPA (U.S. Environmental Protection Agency, 2011): Not Listed
IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): Not Listed
NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
MAK (DFG, 2002): Not Listed
NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

TOXICITY AND RISK ASSESSMENT VALUES

EPA IRIS

EPA Risk Assessment Values for CAS16941-32-5 (U.S. Environmental Protection Agency, 2011):

Not Listed

-STANDARDS AND LABELS

WORKPLACE STANDARDS

ACGIH TLV Values for CAS16941-32-5 (American Conference of Governmental Industrial Hygienists, 2010):

Not Listed

AIHA WEEL Values for CAS16941-32-5 (AIHA, 2006):

Not Listed

NIOSH REL and IDLH Values for CAS16941-32-5 (National Institute for Occupational Safety and Health, 2007):

Not Listed

OSHA PEL Values for CAS16941-32-5 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):

Not Listed

OSHA List of Highly Hazardous Chemicals, Toxics, and Reactives for CAS16941-32-5 (U.S. Occupational Safety and Health Administration, 2010):

Not Listed

ENVIRONMENTAL STANDARDS

EPA CERCLA, Hazardous Substances and Reportable Quantities for CAS16941-32-5 (U.S. Environmental Protection Agency, 2010):

Not Listed

EPA CERCLA, Hazardous Substances and Reportable Quantities, Radionuclides for CAS16941-32-5 (U.S. Environmental Protection Agency, 2010):

Not Listed

EPA RCRA Hazardous Waste Number for CAS16941-32-5 (U.S. Environmental Protection Agency, 2010b):

Not Listed
Editor's Note: The D, F, and K series waste numbers and Appendix VIII to Part 261 -- Hazardous Constituents were not included. Please refer to 40 CFR Part 261.

EPA SARA Title III, Extremely Hazardous Substance List for CAS16941-32-5 (U.S. Environmental Protection Agency, 2010):

Not Listed

EPA SARA Title III, Community Right-to-Know for CAS16941-32-5 (40 CFR 372.65, 2006; 40 CFR 372.28, 2006):

Not Listed

DOT List of Marine Pollutants for CAS16941-32-5 (49 CFR 172.101 - App. B, 2005):

Not Listed

EPA TSCA Inventory for CAS16941-32-5 (EPA, 2005):

Not Listed

LABELS

NFPA

NFPA Hazard Ratings for CAS16941-32-5 (NFPA, 2002):

Not Listed

-PERSONAL PROTECTION

SUMMARY

Editor's Note: An ERG guide with information appropriate to this material does not exist.

PROTECTIVE CLOTHING

CHEMICAL PROTECTIVE CLOTHING. Search results for CAS 16941-32-5.

Specific recommendations and test data for this chemical were not found in the available manufacturers' product literature. A complete list of consulted manufacturers and references is presented below.

-PHYSICAL HAZARDS

FIRE HAZARD

SUMMARY

Editor's Note: An ERG guide with information appropriate to this material does not exist.

FLAMMABILITY CLASSIFICATION

NFPA Flammability Rating for CAS16941-32-5 (NFPA, 2002):

Not Listed

FIRE CONTROL/EXTINGUISHING AGENTS

Editor's Note: An ERG guide with information appropriate to this material does not exist.

NFPA Extinguishing Methods for CAS16941-32-5 (NFPA, 2002):

Not Listed

EVACUATION PROCEDURES

SUMMARY

Editor's Note: An ERG guide with information appropriate to this material does not exist.

AIHA ERPG Values for CAS16941-32-5 (AIHA, 2006):

Not Listed

DOE TEEL Values for CAS16941-32-5 (U.S. Department of Energy, Office of Emergency Management, 2010):

Not Listed

AEGL Values for CAS16941-32-5 (National Research Council, 2010; National Research Council, 2009; National Research Council, 2008; National Research Council, 2007; NRC, 2001; NRC, 2002; NRC, 2003; NRC, 2004; NRC, 2004; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; United States Environmental Protection Agency Office of Pollution Prevention and Toxics, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; 62 FR 58840, 1997; 65 FR 14186, 2000; 65 FR 39264, 2000; 65 FR 77866, 2000; 66 FR 21940, 2001; 67 FR 7164, 2002; 68 FR 42710, 2003; 69 FR 54144, 2004):

Not Listed

NIOSH IDLH Values for CAS16941-32-5 (National Institute for Occupational Safety and Health, 2007):

Not Listed

CONTAINMENT/WASTE TREATMENT OPTIONS

SUMMARY

Editor's Note: An ERG guide with information appropriate to this material does not exist.

SMALL LEAK/SPILL

Editor's Note: An ERG guide with information appropriate to this material does not exist.

LARGE LEAK/SPILL

Editor's Note: An ERG guide with information appropriate to this material does not exist.

-PHYSICAL/CHEMICAL PROPERTIES

MOLECULAR WEIGHT

3483 (Prod Info GlucaGen(R) subcutaneous injection, intramuscular injection, intravenous injection, 2015)

DESCRIPTION/PHYSICAL STATE

GlucaGen is a sterile lyophilized white powder that is soluble in water (Prod Info GlucaGen(R) subcutaneous injection, intramuscular injection, intravenous injection, 2015).

2.5 to 3.5 (Prod Info GlucaGen(R) subcutaneous injection, intramuscular injection, intravenous injection, 2015)

-REFERENCES

GENERAL BIBLIOGRAPHY

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40 CFR 372.65: Environmental Protection Agency - Toxic Chemical Release Reporting, Community Right-To-Know, Chemicals and Chemical Categories to which this part applies. National Archives and Records Association (NARA) and the Government Printing Office (GPO), Washington, DC. Final rules current as of Apr 3, 2006.

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62 FR 58840: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 1997.

65 FR 14186: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2000.

65 FR 39264: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2000.

65 FR 77866: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2000.

66 FR 21940: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2001.

67 FR 7164: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2002.

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69 FR 54144: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2004.

AIHA: 2006 Emergency Response Planning Guidelines and Workplace Environmental Exposure Level Guides Handbook, American Industrial Hygiene Association, Fairfax, VA, 2006.

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Classification | Information to evaluate chemical incidents

Information to evaluate chemical incidents

Information to evaluate chemical incidents

Information to evaluate chemical incidents