Sulfonylureas chlorpropamide

The oral antidiabetic drugs are contraindicated in patients with known hypersensitivity to tiie drugs, DKA, severe infection, or severe endocrine disease. The first generation sulfonylureas (chlorpropamide, tolazamide, and tolbutamide) are contraindicated in patients with coronary artery disease or liver or renal dysfunction. Other sulfonylureas are used cautiously in patients with impaired liver function because liver dysfunction can prolong the drug s effect. In addition, the sulfonylureas are used cautiously in patients with renal... 

The sulfonylureas appear to lower blood glucose by stimulating the beta cells of the pancreas to release insulin. The sulfonylureas are not effective if the beta cells of the pancreas are unable to release a sufficient amount of insulin to meet the individual s needs. The first generation sulfonylureas (, chlorpropamide, tolazamide, and tolbutamide) are not commonly used today because they have a long duration of action and a higher incidence of adverse... 

SULFONYLUREAS Acetohexamide (Dymelor), chlorpropamide (Diabinese), tolazamide (Tolinase), and tolbutamide (Orinase) are given with food to prevent gastrointestinal upset. However, because food delays... 

Allopurinol, aspirin, carbamazepine, chlorpropamide, clomipramine, clozapine, colchicine, desipramine, gold salts, imipramine, levodopa, penicillamine, phenothiazines, phenytoin, propylthiouracil, and sulfonylureas... 

Patients on other oral antidiabetic agents - No transition period is necessary when transferring patients to the extended-release tablets. Observe patients carefully (1 to 2 weeks) when being transferred from longer half-life sulfonylureas (ie, chlorpropamide) to the extended release tablets due to potential overlapping of drug effect. 

Lactation Chlorpropamide and tolbutamide are excreted in breast milk. It is not known if other sulfonylureas are excreted in breast milk. 

Sulfasalazine can inhibit the absorption of cardiac glycosides and folic acid. It may displace certain drugs, including warfarin, phenytoin, methotrexate, tolbutamide, chlorpropamide, and oral sulfonylureas, from their protein binding sites. Sulfasalazine can diminish the effectiveness of penicillins and estrogen-containing oral contraceptives. 

Due to potential for prolonged hypoglycemia, other sulfonylureas should be considered before trying chlorpropamide (especially in the elderly)... 

Tolazamide is comparable to chlorpropamide in potency but 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. 

Tolazamide, tolbutamide, chlorpropamide Older sulfonylureas, lower potency, greater toxicity rarely used ... 

Sulfonylureas [NE] Chlorpropamide is most likely to produce a disulfiram-like reaction acute alcohol intake may increase hypoglycemic effect (especially in fasting patients). 

Increased hepatic metabolism of tolbutamide and probably other sulfonylureas metabolized by the liver (including chlorpropamide). 

Mild hyponatremia has been reported with sulfonylureas, most commonly with chlorpropamide (72,73). The mechanism with chlorpropamide is secretion of ADH... 

Water retention with oliguria, uremia, and edema has been reported with gliclazide (76). Resistance to diuretics can be caused by chlorpropamide (77) or, to a lesser extent, tolbutamide. Changing to a sulfonylurea without an antidiuretic effect (glibenclamide) or to one that enhances water excretion (acetohexamide, glipizide, or tolazamide) (78) may be advisable. 

The most dangerous adverse reaction of sulfonylureas is agranulocytosis. Aplastic anemia (79), red cell aplasia (80), pure white cell aplasia (81), bone marrow aplasia, and hemolytic anemia have been described during treatment with chlorpropamide (82), glibenclamide (83), or tolbutamide (84). 

The risk of hepatotoxicity with the sulfonylureas varies with both the drug and the dosage. It has been described with chlorpropamide (95), tolazamide (96), tolbutamide (97), glipizide (98), and glibenclamide (99). Anicteric, cytolytic hepatitis has been described after glibenclamide (100). 

Hepatic granulomas have been reported as a hypersensitivity reaction to chlorpropamide (101). Cholestatic jaundice from sulfonylureas is also probably of allergic origin it is rare and has been described with glibencla-mide (102), also in combination with hepatorenal syndrome (103), acetohexamide (104), chlorpropamide (105), gliclazide (106), and tolazamide (107). 

Allergic skin reactions have been described with all sulfonylureas. They include pruritic rashes, erythema nodosum, urticaria, blisters (100), erythema multiforme, exfoliative dermatitis, Quincke s edema, erythroderma, and itching, while lichenoid drug reactions with ulceration have occurred after chlorpropamide and tolazamide (124). More generalized hypersensitivity reactions may prove fatal, but rarely. 

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