DM Drugs Toxicity


Sulfonylureas
Agents include
  • Glipizide
  • Glyburide

MECHANISM/TOXICITY

  • Secretion of preformed insulin from pancreatic Beta-cells → hypoglycemia (primary mechanism).
  • Hepatic or renal impairment and drug interactions may be inciting event.

SYMPTOMS/EXAM

  • Most agents require 8 hours to reach peak effect.
  • Symptoms of hypoglycemia
    • Mental status changes, agitation
    • Headache
    • Focal neurologic deficits or seizures
    • Tachycardia, hypertension
    • Diaphoresis
    • Nausea

DIFFERENTIAL

  • Other causes of hypoglycemia including insulin excess, sepsis, hepatic dysfunction.

DIAGNOSIS

  • Usually clear from patient's history and exam
  • Rapid finger-stick glucose can confirm diagnosis of hypoglycemia.

TREATMENT

  • Correct hypoglycemia via dextrose administration.
  • Activated charcoal if recent ingestion and protected airway
  • All patients who become symptomatic should be admitted for 24 hours of observation regardless of response to treatment.
  • Antidote = Octreotide.
    • Long-acting synthetic analog of somatostatin, which inhibits the release of insulin from the pancreas
    • Decreases dextrose requirements and further episodes of hypoglycemia
  • Antidote = diazoxide (3-8mg/kg/day PO divided doses q8-12h, - [50/mL susp]).
    • Antihypertensive/vasodilator, which also inhibits the release of insulin from the pancreas
    • Neither as effective nor as safe as octreotide
    • Reserved for patients who don't respond to octreotide

COMPLICATIONS

  • Disulfiram reactions (headache, flushing, N/V) are possible with all sulfonylureas
    following exposure to alcohol.
Other Antihyperglycemic Agents
Table 6.17 lists other diabetic agents that may present with acute toxicity in
overdose.

 
ANTIHYPERGLYCEMIC CLASS MECHANISM OF ACTION SYMPTOMS/EXAM
Biguanides (metformin) ↑ Peripheral glucose use
↓ Hepatic production and intestinal absorption of glucose.
Lactic acidosis → N/V, malaise, tachypnea.
Does NOT cause hypoglycemia
Glinide derivatives Release of insulin Hypoglycemia (similar to sulfonylureas)
Alpha-Glucosidase inhibitors Delays breakdown of complex carbohydrates in small intestines. No reported toxicity in acute overdose.
Thiazoladinediones ↑ Insulin sensitivity No reported toxicity in acute
overdose