Recurrent hypoglycemia secondary to drug-dispensing error.

We present three patients who developed hypoglycemia due to inadvertent dispensing of sulfonylurea drugs. Each patient had a similar clinical course characterized by hypoglycemia that remitted during hospitalization and recurred after discharge. The cause of the hypoglycemia was determined only after close inspection of the patients' medications, not the label on the container. Our experience suggests that hypoglycemia due to drug-dispensing error may be more common than is generally recognized.

Chlorpropamide-induced hypoglycemia: successful treatment with diazoxide.

A healthy adolescent boy was treated on two occasions for an overdose of chlorpropamide (Diabinese). Glucose therapy alone was not sufficient to control the hypoglycemia, but the administration of glucose plus diazoxide raised the blood sugar to supranormal levels. A bolus of intravenous glucagon briefly raised the blood sugar level to within normal limits, increased the blood ketones but also augmented insulin secretion. An overdose of sulfonylurea may cause prolonged and fatal hypoglycemia. Rational therapy, both in diabetic and normal persons, is glucose plus an "insulin antagonist." The administration of diazoxide was effective in our patient, substantially reducing the plasma insulin level; this agent may be the "insulin-antagonist" of choice for use in sulfonylurea-induced hypoglycemia.

Hyperinsulinaemic hypoglycaemia due to chlorpropamide-induced nesidioblastosis.

A 25 year old woman suffering from recurrent attacks of hypoglycaemia underwent a laparotomy for suspected insulinoma. No tumour was found, but histology showed islet cell hyperplasia and nesidioblastosis. Although these changes have been reported as a cause of hypoglycaemia in infants, they are only rarely the cause of hypoglycaemia in adults; in the present case they were found to be the result of covert sulphonylurea administration. The fact that sulphonylureas can cause nesidioblastosis is not well recognised by either physicians or pathologists and it should be considered before "cryptogenic nesidioblastosis" is deemed the cause of hypoglycaemia in adults.

Diazoxide in the management of chlorpropamide overdose.

Three cases of chlorpropamide overdose are reported. Plasma levels of chlorpropamide, diazoxide, glucose, and insulin are presented for each patient during treatment. The simultaneous analysis of chlorpropamide, hydrochlorothiazide, and diazoxide in plasma by high pressure liquid chromatography (HPLC) is also reported. Although all three cases presented at hospital with potentially lethal plasma levels of chlorpropamide, each was successfully treated with intravenous diazoxide and glucose. Plasma diazoxide concentrations between 50-100 microgram/mL appear to be optimal in achieving therapeutic control of chlorpropamide induced hypoglycemia.

Dispensing error causing fatal chlorpropamide intoxication in a nondiabetic.

A 38-year-old nondiabetic female developed fatal hypoglycemia when chlorpropamide (Diabinese) was accidentally substituted for acetaminophen (Tylenol) with codeine no. 3 in a pharmacy dispensing error. When found, the patient's serum glucose was less than 20 mg/dL. The serum chlorpropamide level on hospital admission was 124 micrograms/mL. The possibility of dispensing error should be considered whenever unexpected drug effects are encountered. In cases of suspected drug overdose, labels and contents of medicine vials found at the scene should be checked for discrepancy.

The interaction between alcohol, chlorpropamide and phenformin in a severe combined poisoning: case report.

A young non-diabetic woman ingested 2.5-3.7 g of chlorpropamide and 0.6-0.9 g of phenformin together with a large dose of alcohol, nitrofurantoin and promethazine in a suicidal attempt. She developed severe metabolic acidosis, hypokalemia, polyuria and prolonged hypoglycemia in the absence of typical hypoglycemic symptoms. These unusual clinical features were in part explained on the basis of the interactions between alcohol and the other drugs.

Treatment of chlorpropamide overdose with diazoxide.

A patient who took a chlorpropamide overdose was treated for several hours with concentrated glucose solutions, with little success in maintaining adequate serum glucose concentrations. Intravenous diazoxide administration was begun with the hope of decreasing pancreatic insulin release. After diazoxide was begun, glucose requirements decreased dramatically, and serum glucose was supranormal for most of the period of diazoxide administration. The case was complicated by the fact that the patient had taken three agents that can cause hypoglycemia--chlorpropamide, alcohol, and aspirin. Drug interactions potentiating the hypoglycemic effect of the chlorpropamide were also possible. Glucose infusion is the mainstay of therapy for a sulfonylurea overdose. However, glucose acts as a further stimulus of insulin release from a sulfonylurea-primed pancreas. Administration of concentrated glucose solutions is technically difficult because of damage to veins. Metabolic consequences of high rates of glucose infusion to hyperinsulinemic patients include hypokalemia and hypophosphatemia. Diazoxide appeared to decrease the glucose requirement in this patient, as it did in three other reported cases. Diazoxide is approved for certain hypoglycemic, hyperinsulinemic conditions. Sulfonylurea overdose represents a hypoglycemic, hyperinsulinemic condition; diazoxide appears to be an effective treatment.

Chlorpropamide toxicity with survival despite 27-day hypoglycemia.

CASE REPORT: In the past 5 years at our institution, 12 cases involving the ingestion of chlorpropamide 3-15 g were fatal. We report a 23-year-old woman with an estimated ingestion of chlorpropamide 5-10 g. Initial cardiovascular collapse, attributed to the blockade of potassium channel transport, responded to intensive support including 3 days of cardiac pacing. Urinary excretion of chlorpropamide and hypoglycemia persisted until day 27. The toxic mechanisms and high risk of chlorpropamide are summarized. A fatal therapeutic dose ratio as low as 4:1 has made this antidiabetic agent obsolete.

Chlorpropamide overdose in renal failure: management with charcoal hemoperfusion.

A potentially lethal chlorpropamide overdose in a patient with chronic renal failure on long-term hemodialysis was treated by two courses of charcoal hemoperfusion. Hemoperfusion shortened the half-life clearance of the drug from a mean value of 93.6 to 3.4 hours. Calculation of the fractional extraction indicated that hemoperfusion reduced the body burden of the drug by 24% and 19% (mean values) during the first and second hours of treatment, respectively. We conclude that charcoal hemoperfusion should be considered a definitive therapeutic option in such cases.

Case report. Computed tomography of the brain in severe hypoglycaemia.

Computed tomographic (CT) findings in a case of extreme hypoglycaemia induced by an overdose of chlorpropamide are described. Brain lesions tend to be preferentially localized along the boundary zones ("watersheds") between the territories of the main cerebral arteries. In our case, generalized brain damage occurred during severe hypoglycaemic coma. Neuropathological changes in this condition have been the subject of previous studies in experimental animals. Computed tomography allows follow-up studies of the human brain damaged by hypoglycaemic coma. Abnormalities revealed by CT probably represent reparative tissue reactions that indirectly reflect the extent of neuronal destruction.