A number of medications apart from the sulfonylureas can occasionally cause hypoglycemia. Common offenders include the fluoroquinolones such as gatifloxacin and levofloxacin, pentamidine, quinine, ACE inhibitors, salicylates and beta-adrenergic blocking agents. The fluoroquinolones, particularly gatifloxacin, have been associated with both hypoglycemia and hyperglycemia. It is thought that the drug acts on the ATP sensitive potassium channels in the beta cell. Hypoglycemia is an early event, and hyperglycemia occurs several days into therapy. Intravenous pentamidine is cytotoxic to beta cells and causes acute hyperinsulinemia and hypoglycemia followed by insulinopenia and hyperglycemia. Fasting patients taking noncardioselective beta-blockers can have an exaggerated hypoglycemic response to starvation. The beta-blockade inhibits fatty acids and gluconeogenesis substrate release and reduces plasma glucagon response. Therapy with ACE inhibitors increases the risk of hypoglycemia in patients who are taking insulin or sulfonylureas presumably because these drugs increase sensitivity to circulating insulin by increasing blood flow to the muscle. Some opioids cause hypoglycemia. Tramadol use has been associated with increased risk of hospitalization for hypoglycemia. Methadone overdose has also been reported to cause hypoglycemia and a rapid dose escalation of methadone in cancer patients can lower glucose levels.
Ethanol-associated hypoglycemia may be due to hepatic alcohol dehydrogenase activity depleting NAD. The resultant change in the redox state—increase in NADH to NAD+ ratio—causes a partial block at several points in the gluconeogenic pathway. With prolonged starvation, glycogen reserves become depleted within 18–24 hours and hepatic glucose output becomes totally dependent on gluconeogenesis. Under these circumstances, a blood concentration of ethanol as low as 45 mg/dL (9.8 mmol/L) can induce profound hypoglycemia by blocking gluconeogenesis. Neuroglycopenia in a patient whose breath smells of alcohol may be mistaken for alcoholic stupor. Prevention consists of adequate food intake during ethanol ingestion. Therapy consists of glucose administration to replenish glycogen stores until gluconeogenesis resumes.
When sugar-containing soft drinks are used as mixers to dilute alcohol in beverages (gin and tonic, rum and cola), there seems to be a greater insulin release than when the soft drink alone is ingested and a tendency for more of a late hypoglycemic overswing to occur 3–4 hours later. Prevention would consist of avoiding sugar mixers while ingesting alcohol and ensuring supplementary food intake to provide sustained absorption.