Hypoglycaemia chlorpropamide

Two main effects occur here. First, change in the pH of urine—weak bases, such as pethidine, are more easily excreted in an acid urine while alkalinisation promotes excretion of weak acids, such as salicylates and phenobarbital. Second, drugs that compete for an active excretion mechanism will reduce each other s elimination—probenecid was used in the early days of penicillin to conserve the drug, while less desirable interactions also occur, e.g. chlorpropamide and phenylbutazone interact to give increased levels of chlorpropamide and a danger of hypoglycaemia. 

BORTEZOMIB ANTIDIABETIC DRUGS-CHLORPROPAMIDE Likely to t hypoglycaemic effect of chlorpropamide Unknown Watch for and warn patients about symptoms of hypoglycaemia - For signs and symptoms of hypoglycaemia, see Clinical Features of Some Adverse Drug Interactions, Hypoglycaemia... 

Chlorpropamide and tolbutamide are excreted in breast milk. Data on other sulphonylureas are not available. Because of the potential for hypoglycaemia in nursing infants, it has to be decided whether to discontinue nursing or to discontinue the drug. 

Data on relative safety suggest that chlorpropamide is the most toxic sulphonylurea (Ferner, 1988), but glyburide causes more dangerous hypoglycaemias than chlorpropamide. Glibenclamide has been shown to have a delayed effect on stimulating insulin secretion and this may be responsible for many unexpected severe hypoglycaemic episodes (Turner et al., 1987). 

Dicoumarol. A 67-year-old non-diabetic man taking chlorpropamide for Parkinson s disease developed severe hypoglycaemia about 3 months after starting dicoumarol. He had high chlorpropamide levels with a half-life of 80 to 90 hours. Dicoumarol was withdrawn, and 3 weeks later his chlorpropamide half-life was 30 hours. This observation prompted further study in 3 other patients and 2 non-diabetics. Dicoumarol doubled the serum chlorpropamide levels within 3 to 4 days and also more than doubled the half-life. ... 

Information is very limited. Only gliclazide has been implicated in severe hypoglycaemia with allopurinol and there seem to be no reports of either grossly enhanced hypoglycaemia with chlorpropamide and allopurinol, or a reduced effect with tolbutamide and allopurinol. More study is needed to find out whether any of these interactions has general clinical importance, but it seems unlikely. 

After taking fluconazole 100 mg daily for 7 days, the AUC of single 250-mg doses of chlorpropamide was increased by 28% in 18 healthy subjects but the maximum plasma levels and blood glucose levels were unchanged. There was no evidence of hypoglycaemia. ... 

Acebutolol appears to inhibit the effeets of glibenclamide, but has no effect on tolbutamide. Also, two isolated cases of hypoglycaemia have been seen with acebutolol, in one patient taking gliclazide and one patient taking chlorpropamide. ... 

A diabetic patient receiving insulin experienced postural syncope and hypoglycaemia, which required a reduction in insulin dose, when mebana-zine was also taken4 Other reports in diabetics indicate that mebanazine increases the blood glucose-lowering effects of insulin, tolbutamide and chlorpropamide, and improves diabetic control. " ... 

The blood glucose-lowering effects of acetohexamide, chlorpropamide, carbutamide, glymidine, glibenclamide yburide) and tolbutamide can be increased by phenylbutazone. Severe hy-poglycaemia has occurred in a few patients. Similarly, azapropa-zone can increase the effects of tolbutamide and cause severe hypoglycaemia. Oxyphenbutazone may be expected to behave similarly. Metamizole (dipyrone) and mofebutazone did not interact with glibenclamide. 

A patient taking chlorpropamide (initially 25 mg increased to 75 mg daily) developed marked hypoglycaemia 3 days after starting nortriptyline 125 mg daily. The chlorpropamide was stopped. ... 

Studies in diabetics have shown that chloramphenicol 2 g daily can increase the serum level and half-life of tolbutamide twofold, and two to threefold, respectively. Blood glucose levels were reduced by about 25 to 30%. Hypoglycaemia, acute in one case, developed in two other patients taking tolbutamide with chloramphenicol. In another study ehloram-phenicol 1 to 2 g daily caused an average twofold increase in the half-life of chlorpropamide.°... 

Chloramphenicol inhibits the liver enzymes concerned with the metabolism of tolbutamide, and probably chlorpropamide as well, leading to their accumulation in the body. This is reflected in prolonged half-lives, reduced blood glucose levels and occasionally acute hypoglycaemia. " ... 

There are several sulphonylureas hut there is no evidence for any difference in their effectiveness. Only chlorpropamide has appreciably more side effects, mainly because of its prolonged duration of action and the consecjuent hazard of hypoglycaemia (but also as a result of the common and unpleasant chlorpropamide-alcohol flush phenomenon). ... 

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