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9780521704632c24 CUFX213A/Peck 9780521618168 December 29, 2007 15:7
24 Drugs used in DiabetesMechanism of action
Thiazolidinediones activate peroxisome proliferator-activated receptorγ(PPARγ–
situated within the cell nucleus) and thereby regulate a number of genes involved in
glucose and lipid metabolism. As a result they act to improve insulin sensitivity.Other effects
They may cause fluid retention and should not be given to those with significant
heart failure.Kinetics
Both drugs are extensively metabolized by hepatic cytochrome P450. Rosiglitazone
metabolites are essentially inactive and mainly excreted in the urine. Some of the
pioglitazone metabolites are active and are excreted in faeces and urine. Neither
drug appears to have interactions with other drugs utilising the cytochrome P450
system.Meglitinides
Repaglinide and metiglinide
Meglitinides are oral antidiabetic agents that may be of most use in treating patients
with erratic eating habits as they are relatively short acting. They are taken just before
meals.Mechanism of action
Meglitinides block the potassium channels in beta cells in the pancreas, closing the
ATP-dependent potassium channels and opening the cells’ calcium channels. The
resulting calcium influx causes the cells to secrete insulin.Kinetics
Repaglinide has an oral bioavailability of 50%, is 98% plasma protein bound and is
metabolized in the liver by CYP3A4 and therefore is potentially susceptible to drug
interactions. Its elimination half-life is 1 hour.Peri-operative care of the diabetic patient
Aregional technique is often more appropriate as the patient will be able to eat and
return to their normal drug regime more rapidly.
Ifageneral anaesthetic is indicated the aim is to minimize the metabolic derange-
ment by providing a balance of fluid, electrolytes, glucose and insulin. There is no
single best way to achieve this and the approach chosen will reflect the type of dia-
betes, medication and proposed operation.