You are in: eMedicine Specialties > Pediatrics: Cardiac Disease and Critical Care Medicine > Toxicology Toxicity, Oral Hypoglycemic AgentsArticle Last Updated: Apr 3, 2006AUTHOR AND EDITOR INFORMATIONSection 1 of 10
  Author: David Tran, MD, Department of Emergency Medicine, NSUH-LIJ at Plainview David Tran is a member of the following medical societies: American Academy of Emergency Medicine and American College of Emergency Physicians Coauthor(s): Michael Lucchesi, MD, Chair, Associate Professor, Department of Emergency Medicine, State University of New York at Brooklyn Editors: Michael E Mullins, MD, Assistant Professor, Department of Emergency Medicine, Washington University School of Medicine; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc; Jeffrey R Tucker, MD, Assistant Professor, Department of Pediatrics, Division of Emergency Medicine, University of Connecticut and Connecticut Children's Medical Center; Paul D Petry, DO, FACOP, FAAP, Consulting Staff, Freeman Pediatric Care, Freeman Health System; Maureen Strafford, MD, Arnold P Gold Foundation Associate Professor, Departments of Anesthesiology and Pediatrics, Tufts University and Tufts-New England Medical Center Author and Editor Disclosure Synonyms and related keywords: oral hypoglycemic agents, sulfonylurea, glyburide, glipizide, glimepiride, tolbutamide, chlorpropamide, tolazamide INTRODUCTIONSection 2 of 10
  BackgroundOral hypoglycemic agents commonly are referred to as sulfonylureas, a class of compounds. Sulfonylurea compounds are among the most widely prescribed medications in the world. The drugs frequently are used to treat patients with type II diabetes. Wide availability of these medications increases potential for either intentional or unintentional overdose in pediatric and adult populations. First-generation sulfonylurea compounds became widely available in 1955. They are acetohexamide, chlorpropamide, tolazamide, and tolbutamide. First-generation agents have longer half-lives (eg, 49 hours for chlorpropamide). Second-generation sulfonylureas were introduced in 1984. Known as glipizide, glyburide, and glimepiride, second-generation sulfonylureas are more potent and have shorter half-lives than the first-generation sulfonylureas. Other agents besides sulfonylureas are employed to treat type II diabetes, including biguanides, alpha-glucosidase inhibitors, and troglitazone. Metformin (Glucophage in the United States) is one such agent. Even in excessive dosage, these agents do not decrease serum glucose below euglycemia; consequently, they are referred to appropriately as antihyperglycemic agents rather than hypoglycemic agents. PathophysiologySulfonylureas are sulfonamide derivatives, but they do not have any antibacterial activity. The exact mechanism of sulfonylureas' hypoglycemic effect remains to be elucidated. These drugs mainly are effective in patients with functional pancreatic beta cells. Sulfonylureas bind to receptors that are associated with potassium channels sensitive to adenosine triphosphate in beta-cell membrane. The binding inhibits efflux of potassium ions from the cells, resulting in depolarization, influx of calcium ions, and release of preformed insulin. Sulfonylureas also may cause the decrease of serum glucagon and potentiate the action of insulin at the extrapancreatic tissues. FrequencyUnited StatesThe American Association of Poison Control Centers' (AAPCC) National Data Collection System compiles an annual report of human poison exposure cases. The number of exposures to oral hypoglycemic agents increased steadily from 1989-1997. Most exposures are in the pediatric population and are due to unintentional ingestion (see Table 1). Table 1. The American Association of Poison Control Centers' National Data Collection System from 1989-1997
*Denotes patients aged 6-17 years
Overall mortality includes adult and pediatric cases RaceNo racial predilection has been reported. SexNo sex predilection exists. AgeToxicity can occur in all ages. Most hypoglycemic overdoses occur in persons aged 6-19 years. CLINICALSection 3 of 10
HistoryA single tablet of sulfonylurea has been reported to produce hypoglycemia in a child. Glipizide has been reported to produce hypoglycemia within 5 minutes of ingestion in an adult. A child can become hypoglycemic after ingestion of 1 glipizide 5-mg tablet. Patients usually become symptomatic within 2 hours of ingestion. Symptoms of hypoglycemia may be delayed if food is taken with the oral hypoglycemic agents. Symptoms may include the following:
PhysicalPatient presentation depends upon the severity and duration of hypoglycemia. In the nondiabetic individual, signs and symptoms of hypoglycemia may not occur until serum glucose is less than 40 mg/dL. Signs may include the following:
CausesSulfonylurea compounds are widely available, contributing to unintentional exposures to oral hypoglycemic agents in the pediatric population. DIFFERENTIALSSection 4 of 10
Adrenal Insufficiency Carnitine Deficiency Fructose 1-Phosphate Aldolase Deficiency (Fructose Intolerance) Galactose-1-Phosphate Uridyltransferase Deficiency (Galactosemia) Glycogen-Storage Disease Type I Growth Hormone Deficiency Hyperinsulinemia Toxicity, Ethanol Toxicity, Salicylate
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| Drug Name | Dextrose (D-glucose) |
|---|---|
| Description | Used to promptly elevate serum glucose. Monosaccharide absorbed from intestine and then distributed, stored, and used by tissues. Parenterally injected dextrose is used in patients who are unable to sustain adequate oral intake. Direct oral absorption results in a rapid increase in blood glucose concentrations. Effective in small doses. No evidence suggests that it may cause toxicity. Concentrated dextrose infusions provide higher amounts of glucose and increased energy intake in a small volume of fluid. |
| Adult Dose | 10-25 g (40-100 mL of 25% dextrose) IV bolus; may follow with continuous IV infusion according to patient requirements |
| Pediatric Dose | Symptomatic hypoglycemia: 0.5-1 g/kg (2-4 mL/kg of 25% dextrose) IV bolus Dextrose solution should be 25% dextrose for children and 10% dextrose for neonates; symptomatic patients need continuous IV infusion of 10% dextrose; rate of infusion can be adjusted to a fingerstick glucose, which should be maintained >100 mg/dL or to the patient's state of euglycemia |
| Contraindications | Anuria; diabetic coma (if blood sugar levels are extremely high); hepatic coma; glucose-galactose malabsorption syndrome; use with caution in patients who are severely dehydrated; do not administer concentrated solution if intraspinal or intracranial hemorrhage is present |
| Interactions | Caution when administering parenteral fluids to patients who are receiving corticosteroids or corticotropin, especially if the solution contains sodium ions |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | May cause nausea, which also may occur with hypoglycemia; IV dextrose solutions may result in dilution of serum electrolyte concentrations or overhydration when fluid overload occurs; use with caution in patients who are suffering from congested states or pulmonary edema; hypertonic dextrose that is administered peripherally may cause thrombosis (administer through central venous catheter instead); caution in subclinical diabetes mellitus or carbohydrate intolerance; increased risk of inducing significant hyperglycemia or hyperosmolar syndrome if solution is administered rapidly, especially in patients with chronic uremia or carbohydrate intolerance; do not administer concentrated solutions SC or IM; rates of dextrose infusion >0.5 g/kg/h may produce glycosuria; at infusion rates of 0.8 g/kg/h the incidence of glycosuria is 5%; monitor fluid balance, electrolyte concentrations, and acid-base balance closely; may produce vitamin B-complex deficiency; large IV boluses of 50% dextrose can cause seizure, hyperosmolar coma, and death in children |
| Drug Name | Glucagon |
|---|---|
| Description | Extracted from beef and pork pancreas. Chemically unrelated to insulin, glucagon is a single-chain polypeptide with 29 amino acid residues and a molecular weight of 3,483. In patients with insulinoma, IV administration of glucagon produces an initial increase in blood glucose; however, because of glucagon's insulin-releasing effect, it may cause the insulinoma to release its insulin and subsequently cause hypoglycemia. Glucagon increases blood glucose concentration and is used to treat hypoglycemia. It is effective in small doses, and no evidence of toxicity has been reported with its use. Glucagon acts only on liver glycogen, converting it to glucose. Parenteral administration of glucagon produces relaxation of the smooth muscle of the stomach, duodenum, small bowel, and colon. The half-life of glucagon in plasma is approximately 3-6 min, similar to that of insulin. |
| Adult Dose | 1 mg/dose IV/IM/SC |
| Pediatric Dose | <20 kg: 0.5 mg/dose IV/IM/SC or dose equal to 20-30 mcg/kg; not to exceed 1 mg/dose >20 kg: Administer as in adults Glucagon can be administered by IV/IM/SC; if no response occurs within 15 min, glucagon can be repeated up to 2 additional doses |
| Contraindications | Documented hypersensitivity; pheochromocytoma |
| Interactions | Effects of anticoagulants may be enhanced by glucagon (although onset may be delayed); monitor prothrombin activity and for signs of bleeding in patients receiving anticoagulants; adjust dose accordingly |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | Helpful only if liver glycogen is available; can cause hypoglycemia in patients with insulinoma; may lead to elevated blood pressure from stimulation of catecholamine release |
Insulin secretion may be altered by various mechanisms. Diazoxide inhibits pancreatic secretion of insulin, stimulates glucose release from the liver, and stimulates catecholamine release, which elevates blood glucose levels. It causes a false-negative insulin response to glucagon.
Octreotide is a peptide with pharmacologic action similar to somatostatin, which inhibits insulin secretion.
| Drug Name | Diazoxide (Proglycem, Hyperstat) |
|---|---|
| Description | Increases blood glucose by inhibiting pancreatic insulin release and possibly through an extrapancreatic effect. Hyperglycemic effect begins within an hour and usually lasts a maximum of 8 h with normal renal function. |
| Adult Dose | 3-8 mg/kg/d IV divided bid/tid q8-12h Refractory hypoglycemia may require higher dosages |
| Pediatric Dose | Hyperstat: 1-3 mg/kg slow IV over 30 min and up to qid |
| Contraindications | Documented hypersensitivity; aortic coarctation; pheochromocytoma; arteriovenous shunts; aortic aneurysm |
| Interactions | May decrease serum hydantoins, possibly resulting in decreased anticonvulsant effects; thiazide diuretics may potentiate hyperuricemic and antihypertensive effects of diazoxide |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Hypotension and sodium retention may occur; patients with diabetes mellitus may require treatment for hyperglycemia; when administered prior to delivery, may produce fetal or neonatal hyperbilirubinemia, thrombocytopenia, altered carbohydrate metabolism, and other adverse reactions |
| Drug Name | Octreotide (Sandostatin) |
|---|---|
| Description | Acts primarily on somatostatin receptor subtypes II and V. A somatostatin analogue, which activates G-protein K channel. Hyperpolarization of the beta cell results in inhibition of Ca influx and insulin release. Octreotide is also used for acromegaly, carcinoid tumors, and Vipomas. |
| Adult Dose | 50 mcg SC tid; adjust dose according to blood glucose |
| Pediatric Dose | 1 mcg/kg SC q12h; in severe refractory cases, continuous IV infusion can be started at 15 ng/kg/min and titrated to response; typically, no further treatment is necessary of a single dose of octreotide |
| Contraindications | Documented hypersensitivity |
| Interactions | May reduce effects of cyclosporine; patients on insulin, oral hypoglycemics, beta-blockers, or calcium channel blockers may need dosage adjustments |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | Experience with octreotide administration in children is limited; adverse effects mainly involve the GI tract and include diarrhea, vomiting, steatorrhea, and abdominal distension; because of alteration in counter-regulatory hormones (eg, insulin, glucagon, GH), hypoglycemia or hyperglycemia may be observed; bradycardia, cardiac conduction abnormalities, and arrhythmias have been reported; due to inhibition of TSH secretion, hypothyroidism may occur; use with caution in patients with renal impairment (decrease dose); cholelithiasis may occur |
Toxicity, Oral Hypoglycemic Agents excerpt
Article Last Updated: Apr 3, 2006
