Antidiabetic drugs sulfonylureas

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... 

When oral antidiabetic drug are combined with other antidiabetic drug (eg, sulfonylureas) or insulin, the hypoglycemic effect may be enhanced. Elderly, debilitated, or malnourished patients are more likely to experience hypoglycemia... 

The oral antidiabetic drugs are the sulfonylureas, metformin, acarbose, thiazolidinediones, and repaglinide. 

Mechanosynthetic protocol optimized for sulfonylureas was also applied to preparation of antidiabetic drug glibenclamide 216 (Scheme 3.55). Synthesis was carried out in two reaction steps first, coupling of benzoic acid derivative 212 and p-(2-aminoethyl)... 

There are about 15 million estimated diabetics in the USA, half of whom have been diagnosed with the disease. More than 1.5 million diabetics are treated with injected insulin and the rest with weight loss, diet, and oral antidiabetic drugs, e.g., sulfonylureas (Tolbutamide, Tolazamide, Chloro-propamide, Glipizide, Glyburid 16). 

Sulfonylureas represent the first class of oral antidiabetes agents approved for use in the United States. These drugs are classified as being either first- or second-generation agents. Both classes of sulfonylureas are equally effective when given at... 

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. 

G. Muller, The molecular mechanism of the insulin-mimetic/sensitizing activity of the antidiabetic sulfonylurea drug amaryl. Mol. Med., 2000, 6, 907-933. 

Of the 2,100,000 diagnosed diabetics in the United States today, 45% are on oral drugs, 33% are on insulin, and 22% are on diet alone. Approximately one million Americans take either tolbutamide or chlorpropamide every day as primary therapy for their diabetes mellitus. The sulfonylureas represent a very significant contribution to medical therapy. That guanidine bases depress blood sugar was first reported in 1918 by Watanabe (27). The real story of the antidiabetic sulfonamides began in 1942. 

Molecular modification of the azo dyes has led to the antibacterial sulfanilamide drugs. Further modification has led to the antidiabetic sulfonylureas. 

Fig. 6. (continued). In other cases, especially if a more potent drug is to be added, which relies on a similar mechanism (e.g., incretin-mediated insulinotropic activity), one of the previously used antidiabetic agents may need to be discontinued (e.g., when adding a sulfonylurea or an incretin mimetic to a patient previously treated with a DPP-4 inhibitor). Note that sufficient study results (see Fig. 5) are not available for all mentioned combinations to provide a sound scientific basis for their use outside clinical studies. 

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