What are the undesirable effects of sulfonylureas

The most important undesirable effect is hypoglycaemia, which is usually manifested after the omission of a meal or generally from the inability to eat food for various reasons. Old age and various coexisting diseases (like Addison's disease) are aggravating factors for the manifestation of hypoglycaemia and should be taken into account. Situations that prolong the excretion of the medicine's metabolites (renal or hepatic insufficiency) or other medicines that augment their actions can cause hypoglycaemia. However, studies regarding the safety of second generation sulfonylureas show, for this point, conflicting results. It should also be noticed that glimepiride causes noticeable fewer and milder episodes of hypoglycaemia compared to glibenclamide. This is due to the proportionally smaller insulin secretion that glimepiride causes.

The management of severe episodes of hypoglycaemia in patients treated with sulfonylureas is done in hospital and the patients should be monitored for 48-72 hours. Injections of repeated boluses of glucose solution 35 percent as well as iv infusions of 10 or 20 percent glucose solution are performed. The administration of glucocorticoids may also be required (see Chapter 5).

An increase of body weight, mainly because of blood sugar control and the restriction of glucosuria, is observed after the reception of most sulfonylureas, with differences that are likely due to the bigger or smaller insulin secretion. For this reason, glimepiride is considered preferable in overweight individuals compared to glibenclamide.

Other undesirable effects, however infrequent, are nausea, vomiting and non-specific gastrointestinal disturbances, as well as rashes. Very seldom, haemolytic anaemia, agranulocytosis (for first generation sulfonylureas), jaundice/cholestasis or granulomatous hepatitis and allergy have been reported. Most undesirable effects are expressed in the first 2-3 months of reception of the medicine.

Chlorpropamide has been reported as causing water retention and hyponatraemia (antidiuretic action), and also flushing after alcohol ingestion, a phenomenon that infrequently can also be caused by glibenclamide.


An 85 year old man, a nursing home resident, was transported to the emergency room because of communication disturbances and the inability to receive food and water. This had been observed for the previous 12 hours and had worsened gradually up to the point of coma. During the previous week, the patient had received bromazepam tablets (Lexotanil) because of insomnia. The patient suffered from Type 2 DM, treated for the last ten years with three doses of glibenclamide 5 mg daily. The last dose had been received in the morning of the same day, six hours before his presentation to the hospital, and the previous evening, together with glibenclamide, he had received two aspirin tablets because of lumbago. At the same time he was being treated with anticoagulants and allopurinol. Before the arrival of the ambulance, the nursing home personnel measured the blood glucose level which was found to be 'Low', (too low to measure). They tried to give him a solution of sugar by mouth, without success.

In the emergency room, the patient opened his eyes and reacted to pain but could not speak. His body weight was 60 kg (132.3 lb) and he was afebrile. The blood glucose meter showed a capillary blood glucose level of 55 mg/dl (3.05 mmol/L), and he was already receiving an infusion of glucose solution 10 percent. Five ampoules of 35 percent, 10 ml, glucose solution were injected intravenously. The serum creatinine was 3.2 mg/dl (282.9 mmol/L). Twenty minutes after the beginning of the infusion, the plasma glucose was 36 mg/dl (2.0 mmol/L). He was given 1 mg glucagon intravenously with a temporary response of his consciousness level and increase of the blood glucose to 90 mg/ dl (5.0 mmol/L). During the next 24 hours, repeated blood glucose measurements showed levels between 60 mg/dl (3.3 mmol/L) and 90 mg/dl (5.0 mmol/L). The infusion of the 10 percent glucose solution was continued and at the end of the second day his blood sugar level ranged between 130 mg/dl (7.2 mmol/L) and 160 mg/dl (8.9 mmol/L). His consciousness was restored and he was given frequent carbohydrate-containing meals.

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