Oral Antidiabetic Agents - Luzimar Teixeira

394 Krentz & Bailey
caemia is more likely with longer-acting sulpho- patients receiving insulin therapy is orders of magninylureas
such as glibenclamide, with tolbutamide tude higher. However, this does not detract from the
holding the lowest place in the hierarchy of risk (see importance of sulphonylurea-induced hypoglyalso
section 1.1.6). Individuals with irregular eating caemia. Minor recurrent hypoglycaemia should
habits (see section 1.2.3) or excessive alcohol con- prompt a reassessment of the choice of agent and
sumption are at higher risk of sulphonylurea-in- consideration of an alternative secretagogue, for exduced
hypoglycaemia. As mentioned in section ample a rapid-acting insulin releaser (see section
1.1.3, hypoglycaemia is also more likely to occur in 1.2). The treatment schedule, the possibility of drug
patients with satisfactory glycaemic control, as indi- interactions (table IV) and relevant features of the
cated by an HbA1c concentration within, or just patient’s lifestyle, such as diet, meal patterns and
above, the non-diabetic reference range. These pa- alcohol use, should be reviewed. Severe episodes of
tients should always be questioned directly about sulphonylurea-induced hypoglycaemia mandate imrecent
symptoms of hypoglycaemia, although their mediate admission to hospital: treatment with a connonspecific
nature can raise problems of over-diag- tinuous intravenous infusion of dextrose may be
nosis; self-monitoring of capillary blood glucose required for several days. There is a tendency for
concentrations during suggestive episodes should hypoglycaemia to recur shortly after initial resuscihelp
to clarify this issue, although uncertainties may tation with intravenous dextrose; the patient should
not be completely dispelled. If there is continuing not be prematurely discharged after emergency
doubt, a temporary reduction in dose is usually treatment. Where accumulation of chlorpropamide
indicated. Estimates of the incidence of mild hypo- is suspected, renal elimination may be enhanced by
glycaemia, that is, not requiring assistance from forced alkaline diuresis. The vasodilator diazoxide
another individual, are often based on symptoms
and the somatostatin analogue octreotide [24] have
which have not necessarily been confirmed by conbeen
used successfully to reversibly inhibit insulin
temporaneous self-measurement of capillary blood
secretion in severe sulphonylurea-induced hypoglyglucose.
In the UKPDS, for example, about 20% of
caemia, thereby reducing intravenous dextrose resulphonylurea-treated
patients reported one or more
quirements. These drugs should be regarded as poepisodes
suggestive of hypoglycaemia annually;
tentially useful adjuncts to intravenous glucose in
other studies have suggested similar rates. [23] The
some patients; octreotide avoids the adverse haemotiming
of hypoglycaemia tends to reflect the
dynamic effects of diazoxide, an obsolete antihyperpharmacokinetics
of the sulphonylurea. Thus, glitensive
agent that may pose a hazard in the elderly
benclamide has a propensity to cause inter-prandial
patient with compromised cardiovascular reflexes.
hypoglycaemia whereas chlorpropamide tends to
induce hypoglycaemia in the pre-breakfast period. Other adverse events of sulphonylureas include
More severe hypoglycaemia (i.e. requiring assis- uncommon sensitivity reactions – usually cutaneous
tance) occurred in about 1% of sulphonylurea-treatrare.
– that are usually transient; erythema multiforme is
ed patients annually in the UKPDS. In general,
Fever, jaundice and blood dyscrasias are very
lower rates (approximately 0.2–2.5 episodes per rare; some sulphonylureas can reportedly precipitate
1000 patient-years) have been reported from adheyday,
acute porphyria in predisposed individuals. In its
verse event reporting to regulatory authorities or
chlorpropamide was notorious for causing
from physician-completed questionnaires. The morquantities
unpleasant facial flushing after consuming small
tality risk from severe sulphonylurea-induced hyporeported.
of alcohol; photosensitivity has also been
glycaemia has been calculated to be 0.014–0.033 per
Chlorpropamide could also increase renal
1000 patient-years. [23] Predictably, longer-acting sensitivity to antidiuretic hormone, occasionally
high-potency agents, such as glibenclamide, appear causing water retention with hyponatraemia. In con-
to carry the greater mortality risk. For comparison, trast, glibenclamide is credited with a mild diuretic
the occurrence of severe hypoglycaemia induced in action. Weight gain is regarded as a class effect of
© 2005 Adis Data Information BV. All rights reserved. Drugs 2005; 65 (3)