[
Show Section Outline]
DESCRIPTION
- Oral hypoglycemic agents are used primarily in the treatment of type II diabetes mellitus.
- Substances include acetohexamide (Dymelor), carbutamide, chlorpropamide (Diabinese), gliclazide (Diamicron), glimepiride (Amaryl), glipizide (Glucotrol, Glucotrol XL), glybenclamide, glyburide (Micronase, DiaBeta, Glynase), glymidine, metahexamide, tolazamide (Tolinase, Tolamide), and tolbutamide (Orinase, Oramide).
- Metformin is discussed in a separate chapter.
FORMS AND USES
- Chlorpropamide. 100 mg orally every day up to 750 mg/day.
- Glipizide. 5 mg orally every day up to 40 mg/day.
- Glyburide. 2.5 mg orally every day up to 20 mg/day.
- Tolbutamide. 250 mg orally every day up to 3,000 mg divided twice a day.
TOXIC DOSE
One pill may cause hypoglycemia in a nondiabetic child or adult.
PATHOPHYSIOLOGY
- Sulfonylurea agents cause hypoglycemia by stimulating pancreatic insulin release and suppressing glucagon release.
EPIDEMIOLOGY
- Poisoning is common.
- Toxic effects are typically mild following accidental exposure, but may be severe after large, deliberate ingestion.
- Death is rare, occurring in untreated cases with severe hypoglycemia.
- Infants and children have smaller glycogen stores than adults and are prone to developing hypoglycemia.
CAUSES
- Poisoning is usually an accidental incident in a child.
- Therapeutic misadventures are common in adults.
- Child neglect should be considered if patient is less than 1 year of age, suicide attempt if patient is over 6 years of age.
RISK FACTORS
Conditions that decrease sulfonylurea elimination (hepatic and renal insufficiency) or that decrease glycogen stores (starvation, alcohol abuse, hepatic disease) predispose individuals to hypoglycemia.
DRUG AND DISEASE INTERACTIONS
- Hypoglycemia may be potentiated by cimetidine, ethanol, insulin, salicylates, phenylbutazone, sulfonamides, beta-blockers, enalapril, chloramphenicol, gemfibrozil, ranitidine, clofibrate, and warfarin.
- A disulfiram-like reaction may occur upon ingestion of alcohol.
PREGNANCY AND LACTATION
Glimepride
US FDA Pregnancy Category C. The drug exerts animal teratogenic or embryocidal effects, but there are no controlled studies in women, or no studies are available in either animals or women.
Acetohexamide, Chlorpropamide, Glyburide, Tolazamide, and Tolbutamide
- US FDA Pregnancy Category D. Evidence of human fetal risk exists, but benefits in certain situations (e.g., life-threatening situations or serious diseases) may make use of the drug acceptable despite its risks.
- Neonatal hypoglycemia may occur in a child born to a sulfonylurea-treated mother.
Section Outline:
[
Show Section Outline]
DIFFERENTIAL DIAGNOSIS
- Diseases or toxicants that present with hypoglycemia (without hepatic injury) include overdose with insulin or akee fruit, and intoxication with any type of alcohol, especially in children.
- Many medications cause hypoglycemia under certain conditions.
SIGNS AND SYMPTOMS
- Hypoglycemia may be delayed, prolonged, or recurrent.
- With severe hypoglycemia, anxiety, diaphoresis, tremors, tachycardia, lethargy, slurred speech, coma, and seizures may develop.
Vital Signs
Hypoglycemia initially causes tachycardia, tachypnea, and hypertension, followed by hypotension, hypothermia, and respiratory depression with severe prolonged hypoglycemia.
Dermatologic
Hypoglycemia commonly causes diaphoresis.
Pulmonary
Tachypnea and dyspnea occur initially; respiratory depression may occur during prolonged hypoglycemia.
Gastrointestinal
Hunger, nausea, and vomiting may occur as a result of hypoglycemia.
Hepatic
Cholestatic hepatitis has been reported with therapeutic use of acetohexamide or glyburide.
Fluids and Electrolytes
Hyponatremia and inappropriate secretion of antidiuretic hormone (SIADH) have been reported with chlorpropamide and tolbutamide use.
Neurologic
- Lethargy, slurred speech, paresthesia, anxiety, headache, tremors, weakness, and ataxia may occur early, followed by disorientation, agitation, coma, and seizures.
- Focal neurologic signs such as paraplegia are uncommon but may occur.
- Permanent neurologic impairment may follow prolonged hypoglycemia.
Endocrine
Recurrent, severe hypoglycemia that lasts for days may develop after large overdose.
PROCEDURES AND LABORATORY TESTS
Essential Tests
Serum or finger-stick glucose determination should be performed immediately and then hourly.
Recommended Tests
- ECG, serum acetaminophen and aspirin levels in overdose setting to detect occult overdose.
- Serum electrolytes, renal and hepatic function tests, lumbar puncture, and urine toxicology screen as needed to rule out other causes of altered mental status
- Serum insulin, proinsulin, C peptide levels, and urinary sulfonylurea level if surreptitious use of insulin is suspected
- Head CT as needed to rule out other causes of altered mental status.
Not Recommended Tests
Serum levels of sulfonylureas are not clinically useful in overdose.
Section Outline:
[
Show Section Outline]
- Immediate administration of glucose and appropriate airway management are critical.
- Dose and time of exposure should be determined for all substances involved.
DIRECTING PATIENT COURSE
The health-care provider should call the poison control center when:
- Hypoglycemia or other severe effects are present.
- Toxic effects are not consistent with oral hypoglycemic poisoning.
- Coingestant, drug interaction, or underlying disease presents an unusual problem.
The patient should be referred to a health-care facility when:
- Attempted suicide or homicide is possible.
- Patient or caregiver seems unreliable.
- A child or nondiabetic patient has ingested sulfonylurea or any individual has received a sulfonylurea overdose.
- Toxic effects are not consistent with oral hypoglycemic poisoning.
- Coingestant, drug interaction, or underlying disease presents an unusual problem.
Admission Considerations
Inpatient management for serial glucose determinations is warranted for nondiabetic patients who ingest one pill or more.
DECONTAMINATION
Out of Hospital
- Emesis should not be induced.
- The patient should ingest a glucose-containing food or drink (soda or juice with added sugar) immediately if any symptoms of hypoglycemia develop.
In Hospital
- Gastric lavage should be performed in pediatric (tube size 24-32 French) or adult (tube size 36-42 French) patients presenting within 1 hour of a large ingestion or if serious effects are present.
- One dose of activated charcoal (1-2 g/kg) should be administered without a cathartic if a substantial ingestion has occurred within the previous few hours.
ANTIDOTES
Dextrose is a specific antidote.
- Indications are symptoms of hypoglycemia following oral hypoglycemic overdose or glucose less than 60 mg/dl; routine administration of dextrose to a patient with a normal glucose level is not recommended.
- Method of administration
- Adult. 50 ml of D50W (25 grams) by bolus intravenous infusion.
- Child. 1 to 2 ml/kg of D25W.
- Neonate. 1 to 2 ml/kg of D10W.
- Dextrose dose is repeated until blood glucose is greater than 100 mg/dl.
- Blood glucose is followed hourly to guide further therapy.
- Continuous infusion of 5%, 10%, or 20% dextrose is initiated as needed if recurrent hypoglycemia develops.
- Infusion of D20W requires a central venous line to avoid venous injury.
ADJUNCTIVE TREATMENT
Octreotide Acetate
- Indications. Hypoglycemia resistant to glucose administration following sulfonylurea overdose
- Contraindications. Octreotide allergy.
- Method of administration. Continuous infusion of 30 ng/kg/min for approximately 12 to 18 hours, longer if needed due to recurrent hypoglycemia.
- For adults, a dose of 100 µg subcutaneously every 8 hours has been recommended.
- Potential adverse effects. Steatorrhea.
Diazoxide
- Indications. Hypoglycemia resistant to glucose administration following sulfonylurea overdose.
- Contraindications. Diazoxide allergy.
- Method of administration. Adult dose is 300 mg intravenously over 60 minutes, repeated as necessary.
- Potential adverse effects: Hypotension.
Not Recommended Treatment
- Glucagon is not recommended.
- Multiple-dose activated charcoal has been recommended for glipizide, but has not been shown to affect outcome and is not routinely recommended.
- Although the half-life of chlorpropamide is reduced by urinary alkalinization, this has not been shown to affect outcome and is not routinely recommended.
Section Outline:
[
Show Section Outline]
EXPECTED COURSE AND PROGNOSIS
- After significant ingestion, hypoglycemia usually develops within 12 to 16 hours, may last for days and may recur when glucose is weaned.
- Full recovery is expected if prolonged hypoglycemia does not occur.
- Permanent neurologic injury may result from prolonged hypoglycemia.
DISCHARGE CRITERIA/INSTRUCTIONS
- From the emergency department. Asymptomatic patients may be discharged after gastrointestinal decontamination and psychiatric evaluation, when appropriate, and when their serial blood glucose levels are greater than 60 mg/dl without dextrose treatment during an observation period of 12 to 16 hours.
- From the hospital. Asymptomatic patients may be discharged when they are tolerating food and are euglycemic without supplemental dextrose administration for at least 6 hours following psychiatric evaluation, if needed.
Section Outline:
[
Show Section Outline]
DIAGNOSIS
Early infusion of D5W in an asymptomatic patient with a history of ingestion of oral hypoglycemia agents may maintain normal blood glucose and delay diagnosis of serious ingestion.
TREATMENT
Hypoglycemia may recur despite dextrose infusion.
Section Outline:
ICD-9-CM 977Poisoning by other and unspecified drugs and medicinal substances.
See Also: SECTION III, Dextrose chapter; and SECTION IV, Insulin and Metformin chapters.
RECOMMENDED READING
Palatnick W, Meatherall RC, Tenenbein M. Clinical spectrum of sulfonylurea overdose and experience with diazoxide therapy. Arch Intern Med 1991;151:1859-1862.
McLaughlin SA, Crandall CS, McKinney PE. Octreotide: An antidote for sulfonylurea-induced hypoglycemia Ann Emerg Med. In Press.
Author: Lada Kokan
Reviewer: Katherine M. Hurlbut