This document discusses oral hypoglycemic toxicity from sulfonylureas. It notes that sulfonylureas are commonly prescribed to treat type 2 diabetes but can cause hypoglycemia from overdose. Symptoms of hypoglycemia include confusion, dizziness, and seizures. Treatment involves glucose administration via IV or glucagon injection. Patients may require glucose for hours to days depending on the drug and dose. Activated charcoal may help if ingestion was within an hour but has limited benefit for 1-2 tablet ingestions.

1. Oral
hypoglycemic
toxicity

2. sulfonylureas
• Oral 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 are frequently 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

3. • other agents besides sulfonylureas are used 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 agent

4. • A 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:
• Lethargy
• Confusion
• Irritability
• Unresponsiveness
• Dizziness
• Headache
• Blurred vision
• Psychotic behavior
• Emesis
• Delirium
• Feeding difficulties
• Diaphoresis
• Tachycardia
• Tachypnea
• Transient neurologic
deficit
• Seizure
• Cyanosis
• Coma
• Hypothermia

5. Work up
• Fingerstick and/or serum glucose test to detect hypoglycemia
(If hypoglycemia does not occur within the first 2-4 hours after
suspected ingestion/overdose, then other laboratory tests are
unnecessary.)
• Baseline CBC count (in symptomatic patients)
• Baseline electrolytes, especially potassium (in symptomatic
patients)
• Serum aspirin and acetaminophen concentrations, and urine
toxicological screening, if intentional ingestion/suicide attempt
is suspected
• Pregnancy test, if indicated
• Ethanol level, if indicated

6. Medical care
• intravenous administration of glucose rapidly resolves the
effects of hypoglycemia. Its onset is quicker than oral
administration of sugar, and it is safer in patients with a
depressed mental status who should not take anything by
mouth for fear of aspiration.
• Glucagon is helpful and can be administered intravenously,
intramuscularly, or subcutaneously. Glucagon is particularly
useful in the intramuscular mode when intravenous access
cannot be obtained immediately.
• one study suggest that because accidental ingestion of
sulfonylurea results in delayed and often prolonged
hypoglycemia, admission for at least 16 hours is
recommended, with frequent glucose monitoring.

7. • If a patient is lethargic, then oxygen, continuous cardiac
monitoring, and pulse oximeter are indicated. Until the
patient totally regains mental status, do not administer
anything by mouth.
• Depending on the amount of the drug and its half-life,
patients may require intravenous glucose administration
for anywhere from several hours to several days. If
patients do not respond to continuous glucose
administration with supplemental boluses, then octreotide
or diazoxide can be administered.

8. • Ipecac is not recommended because of the possibility of
aspiration in patients with a depressed mental status.
• Administer activated charcoal as soon as possible, preferably
within 1 hour of ingestion; however, most unintentional
pediatric exposure results in ingestion of 1 or 2 tablets of
sulfonylureas. No data indicate that gastric lavage or
administration of activated charcoal has any benefit in these
cases.
• Multiple doses of activated charcoal have been suggested in
patients with glipizide overdose because this hypoglycemic
agent has an enterohepatic circulation.
• Hemodialysis is not indicated because most sulfonylureas have
high protein binding.

9. metformin in the acute
overdose setting
• without hypoglycemia. When lactic acidosis occurs in patients
using therapeutic doses of metformin, it is considered life-
threatening because reported case series demonstrate a death
rate of approximately 50%.
• Hypoglycemia was only seen in patients with concurrent
ingestions of insulin or sulfonylureas.
• Other symptoms reported in scant case reports include lethargy
and disseminated intravascular coagulation (DIC).
• Patients who are not diabetic presented with symptoms of GI
complaints, headache, and dizziness.
• A single case series of children with reports of accidental
metformin exposure found no significant health risk of
hypoglycemia and no evidence of lactic acidosis.

10. • The mechanism thought related to metformin induced
lactic acidosis includes decreased gluconeogenesis from
alanine, pyruvate, and lactate leading to lactate
accumulation.
• The risk of metformin associated lactic acidosis is
increased with concurrent renal insufficiency and
therefore the drug should not be used in these patients.
• Lactic acidosis, associated with biguanide therapy, is
treated with sodium bicarbonate and hemodialysis,
resulting in rapid improvements in acid-base status and
removal of metformin from the blood.

11. Are the
thiolidinediones such as troglitazone,
piaglitazone, and rosiglitazone toxic?
• There is little information regarding overdose with the
thiolidinediones. Overdose information is derived from
adverse effects at therapeutic levels.
• Although infrequently reported, hypoglycemia can occur,
especially when used in a poly-drug regimen.
• Reports of hepatotoxicity occur after therapeutic
troglitazone therapy, but long-term studies especially on
the recently released agents are lacking.