Chlorpropamide is a drug in the sulfonylurea class used to treat diabetes mellitus type 2. It is a long-acting first-generation sulfonylurea. Mechanism of action
Like other sulfonylureas, chlorpropamide acts to increase the secretion of insulin, so it is only effective in patients who have some pancreatic beta cell function. It can cause relatively long episodes of hypoglycemia; this is one reason why shorter-acting sulfonylureas such as gliclazide or tolbutamide are used instead. The risk of hypoglycemia makes this drug a poor choice for the elderly and patients with mild to moderate hepatic and renal impairment. Chlorpropamide is also used in partial central diabetes insipidus. Pharmacokinetics
Maximal plasma concentrations are reached 3 to 5 hours after quick and nearly complete (>90%) resorption from the gut. Plasma half life is 36 hours; the drug is effective for about 24 hours, longer than other sulfonylureas. A stable plasma level is only reached after three days of continuous application. 90% of the drug are bound to plasma proteins; at least two albumin binding sites exist. More than 99% of chlorpropamide are excreted unchanged via the kidneys. It is first filtrated in the glomeruli, then reabsorbed, and finally secreted into the tubular lumen. Cautions and contraindications
Chlorpropamide and other sulfonylureas encourage weight gain, so they are generally not favored for use in very obese patients. Metformin (Glucophage) is considered a better drug for these patients.
In New Guinea (origin of the term "pig-bel"), the disease is usually spread through contaminated meat (especially pork) and perhaps by peanuts. CNE was also diagnosed in post-World War II Germany, where it was known as Darmbrand or "bowel fire," and reached epidemic proportions. The causative agents of these CNE cases have since been described as Type C isolates of C. perfringens, which possessed genes for β-toxins and enterotoxins.In developed countries, CNE can also occur in people with diabetes, including children. This form of CNE is extremely rare: to demonstrate its scope, only three such cases have been reported in the United States up to 2002. Diagnosis
An abdominal x-ray shows multiple dilated loops of small bowel and gas. The abdomen can be tender, distended, and soft. A differential diagnosis can be an intussusception. Treatment
Treatment involves suppressing the toxin-producing organisms with antibiotics such as penicillin G or metronidazole. About half of seriously ill patients require surgery for perforation, persistent intestinal obstruction, or failure to respond to the antibiotics. An investigational toxoid vaccine has been used successfully in some developing countries but is not available outside of research. Antibiotic therapy — For all infants with suspected or established NEC, we suggest initiating broad-spectrum antibiotics after obtaining appropriate specimens for culture. The empiric antibiotic regimen should provide broad-spectrum coverage, including coverage for common causes of late-onset neonatal sepsis. The choice is also guided by the local susceptibility patterns (ie, the local antibiogram in a particular neonatal intensive care unit [NICU]).