Sulfonylureas administration

The most common adverse effect associated with sulfonylurea administration is hypoglycemia, which may be provoked by inadequate calorie intake (e.g., skipping a meal), or increased caloric needs (e.g., increased physical activity). Collectively, sulfonylureas also tend to cause weight gain, which is undesirable in individuals... 

Used in sulfonylurea and quinine intoxication (secondary after glucose administration)... 

Short-term administration Short-term administration of sulfonylureas may be sufficient during periods of transient loss of control in patients usually well controlled on diet. 

Loss of blood glucose control When a patient stabilized on any diabetic regimen is exposed to stress such as fever, trauma, infection, or surgery, a loss of control may occur. At such times, it may be necessary to discontinue the drug and give insulin. Disulfiram-like syncframe. A sulfonylurea-induced facial flushing or breathlessness reaction may occur when some sulfonylureas are administered with alcohol. Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) Water retention and dilutional hyponatremia have occurred after administration of sulfonylureas to type 2 diabetes patients, especially those with CHF or hepatic cirrhosis. 

Sulfonylureas inhibit neoglucogenesis and glycogenolysis. Sulfonylureas are rapidly absorbed from the gastrointestinal tract after oral administration and are more than 90 percent bound to plasma proteins and excreted unchanged in urine. 

Long-term administration of sulfonylureas to type 2 diabetics reduces serum glucagon levels, which may contribute to the hypoglycemic effect of the drugs. The mechanism for this suppressive effect of sulfonylureas on glucagon levels is unclear but appears to involve indirect inhibition due to enhanced release of both insulin and somatostatin, which inhibit alpha-cell secretion. 

Pramlintide is approved for concurrent mealtime administration in individuals with type 2 diabetes treated with insulin, metformin, or a sulfonylurea who are unable to achieve their postprandial glucose targets. Combination therapy results in a significant reduction in early postprandial glucose excursions mealtime insulin or sulfonylurea doses usually have to be reduced to prevent hypoglycemia. 

Repaglinide possesses the same mechanism of action as the sulfonylureas but differs in chemical structure. After oral administration, the effect develops rapidly and fades away quickly. Therefore, repaglinide can be taken immediately before a meal. 

There have been several reports of hepatotoxicity of iodipamide, variously characterized by epigastric pain, nausea and vomiting, jaundice, pyrexia, and tenderness over the liver, with abnormal liver function tests. Biopsy has shown centrilobular necrosis (154). The incidence of abnormal liver function tests may be as high as 18% after a dose of 40 ml, and the quantity given should be as small as possible. Prior administration of glucocorticoids or sulfonylureas impairs hepatic excretion of ioglycamide. Both iodoxamate and iotroxate can affect liver function tests in a small series of cases, the degree of intrahepatic cholestasis appeared to be relatively more marked after iodoxamate than after iotroxate (SED-12, 1168) (155). 

The administration of total parenteral nutrition for periods greater than 1 week induces cholestatic changes and nonspecific enzyme elevations in some patients. Patients with low serum albumin concentrations may be at greater risk than patients with normal serum albumin concentrations. This reaction also has been reported to occur rarely with sulfonamides, sulfonylureas, erythromycin estolate and ethylsuccinate, captopril, fisinoprU, and other phenothiazines. ... 

Although a less potent inducer of CYPs than rifampin, rifabutin does induce hepatic microsomal enzymes, with its administration decreasing the half-life of a number of different compounds, including zidovudine, prednisone, digi-toxin, quinidine, ketoconazole, propranolol, phenytoin, sulfonylureas, and warfarin. It has less effect than does rifampin on serum levels of indinavir and nelfinavir. 

Toxicity Common adverse effects include bone marrow suppression and toxie effects on the skin and gastrointestinal mucosa (mucositis). The toxic effects of methotrexate on normal cells may be reduced by administration of fohnie aeid (leucovorin) this strategy is called leucovorin rescue. Long-term use of methotrexate has led to hepatotoxieity and to pulmonary infiltrates and fibrosis. Salicylates, NSAlDs, sulfonamides, and sulfonylureas enhance the toxicity of methotrexate. 

A report by Lebowitz and Feinglos (41) Indicates that, during chronic administration, part of the hypoglycemic action of the sulfonylureas Is extra pancreatic. Peripheral tissues may become more sensitive to a fixed dose of an administered hormone possibly due to an Increase In the number of insulin receptors. 

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