FIRST-GENERATION SULFONYLUREAS
Tolbutamide is well absorbed but rapidly metabolized in theliver. Its
duration of effect is relatively short, with an elimination half-life of 4–5
hours, and it is best administered in divided doses. Because of its short
half-life, it is the safest sulfonylurea for elderly diabetics. Prolonged
hypoglycemia has been reported rarely, mostly in patients receiving certain
drugs (eg, dicumarol, phenylbutazone, some sulfonamides) that inhibit the
metabolism of tolbutamide.
Chlorpropamide has a half-life of 32 hours and is slowlymetabolized in the
liver to products that retain some biologic activity; approximately 20–30% is
excreted unchanged in the urine. Chlorpropamide also interacts with the drugs
mentioned above that depend on hepatic oxidative catabolism, and it is
contraindicated in patients with hepatic or renal insufficiency. Dosages higher
than 500 mg daily increase the risk of jaundice. The average maintenance dosage
is 250 mg daily, given as a single dose in the morning. Prolonged hypoglycemic
reactions are more common in elderly patients, and the drug is contraindicated
in this group. Other adverse effects include a hyperemic flush after alcohol
ingestion in genetically predisposed patients and dilu-tional hyponatremia.
Hematologic toxicity (transient leukopenia, thrombocytopenia) occurs in less
than 1% of patients.
Tolazamide is comparable to chlorpropamide in potencybut has a shorter
duration of action. Tolazamide is more slowly absorbed than the other
sulfonylureas, and its effect on blood glucose does not appear for several
hours. Its half-life is about 7 hours. Tolazamide is metabolized to several
compounds that retain hypoglycemic effects. If more than 500 mg/d are required,
the dose should be divided and given twice daily.
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