michael s
(Michael S)
#1
38 Are there benefits to switching from
sulphonylureas to insulin after coronary artery
bypass grafting?
Jonathan Unsworth-White
Sulphonylureas help to control blood glucose levels by binding
to adenosine-5-triphosphate(ATP)-sensitive potassium channels
(KAT P-channels) in the beta-cells of the pancreas. This inhibits
potassium flux across the cell membrane, leading to depolari-
sation of the plasmalemma and subsequently the release of
endogenous insulin. These same KAT P-channels are also found in
the myocardium and in vascular smooth muscle cells and are
therefore implicated in the regulation of the cardiovascular
system.
A fall in myocardial cytosolic levels of ATP and a rise in
extracellular adenosine opens the KAT P-channels during
myocardial ischaemia. This is thought to be a natural protective
action, related to the phenomena of preconditioning and
hibernation. Glibenclamide abolishes this effect at clinically
relevant doses and infarct size is increased in animal models of
myocardial ischaemia. These drugs also antagonise the
vasodilating effects of drugs like minoxidil and diazoxide and can
reduce resting myocardial blood flow. In contrast, sulphonylureas
might reduce the incidence of post-ischaemic ventricular
arrhythmias. By blocking KAT P-channels, they prevent the
tendency towards shortening of the action potential during
myocardial ischaemia secondary to potassium efflux through
opened channels.
Secondly, since type II diabetics are both insulin deficient and
insulin resistant, glycaemic control may be improved in some
individuals by combining oral medication with insulin or by
switching completely.
In summary there remain theoretical arguments for and
against changing from sulphonylureas following coronary
surgery. The position may be eased by the development of more
pancreas-specific drugs. For the time being at least, strict
glycaemic control by whatever means should remain the
primary aim, if necessary using short acting, low dose
sulphonylurea derivatives.
