Diabetes Oral Antidiabetic Drugs: Sulphonylureas

Sulphonylureas work by increasing the sensitivity of the beta islet cells of the pancreas to glucose so that they release more insulin in response to the presence of a particular level of blood glucose. They also stimulate the uptake of glucose from the blood by peripheral and muscle tissues and they lower hepatic (liver) production of glucose. Sulphonylureas can only work in people who still have some operational beta cells that are able to produce insulin. There are a number of drugs within the group which act metabohcally in slightly different ways.

One of the principal differences between them is the length of time for which they remain detectable in blood plasma (known as the half-life of the drug), which is a reflection of the length of time for which they remain active. In general, those with a longer half-life pose a greater threat of a more prolonged hypoglycaemia, which is the most severe potential side-effect of these drugs and which in rare cases can cause serious neurological damage or death. All the sulphonylureas remain active, that is, produce glucose-lowering effects, for a longer period than their half-life, although there are differences between them. Some of this group of drugs were developed a long time ago and have been in use for many years.

These are called the first-generation sulphonylureas. Others, termed second-generation, have been developed more recently and generally have greater potency, although they are not necessarily more effective in achieving better glycaemic control. The rate of absorption and hence activity of some of the sulphonylureas is delayed by the presence of food and this has implications for when the tablets have to be taken. Most need to be taken half an hour before meals so that absorption is not delayed and the beta cells can be stimulated to deal with the intake of food. Some of the drugs within the group are eliminated (i.e. excreted) by the kidneys, either unchanged or else as metabolized products which remain active.

Some, on the other hand, are changed or metabolized into inactive compounds by the liver, before being eliminated. People with diabetic nephropathy or any other from of kidney impairment cannot be treated with sulphonylureas which are excreted in an active form. Many clinicians prefer to avoid using these drugs altogether in these circumstances and recommend insulin treatment instead. This may also be the case for elderly people, who are more likely to have altered renal function, particularly a high renal threshold for glucose, and who are also considered to be at greater risk of severe, sulphonylurea-induced hypoglycaemia.

Drugs that have been implicated include:

• alcohol: less likely with modest intake but alcohol can have other side-effects {see below)
• aspirin and other salicylates: familiar painkillers and blood-thinning drugs
• azapropazone (Rheumox): a non-steroidal anti-inflammatory drug (NSAID) used for rheumatoid arthritis, severe gout, ankylosing spondylitis
• cimetidine (Algitec, Dyspamet, Galenamet, Tegamet, Zita): used for digestive disorders, e.g. acid reflux, acid
• chloramphenicol: antibiotic used in various preparations to combat bacterial infections
• clofibrate (Atromid-S): used to treat hyperlipidaemia (raised blood levels of lipids or fats)
• co-trimoxazole: combined antibiotic preparation used in the treatment of urinary tract infections
• cyclophosphamide (Endoxana): used in chemotherapy (more details on chemotherapy here) to treat some malignant conditions
• fluconazole (Diflucan): antifungal agent used to treat fungal infections
• miconazole: antibacterial and antifungal agent used in various preparations to treat infections
• monoamine oxidase inhibitors: various drugs used in special circumstances to treat severe depression, anxiety or phobia
• phenylbutazone (Butacote): an NSAID used only in hospital to treat severe arthritis and other serious inflammatory conditions
• probenecid (Benemid): used to treat gout and sometimes combined with antibiotic therapy
• ranitidine (Zantac): used to treat ulcers in the stomach and gut
• rifampicin (Rifadin, Rifater, Rifinah, Rimactane, Rrimactazid): antibiotic used to treat serious bacterial infections, especially tuberculosis and, in other preparations, as a protection against meningitis
• sulphinpyrazone (Anturan): used to treat gout
• sulphonamides: prevent bacterial growth and used to control infections
• tetracyclines: a large group of antibiotics used to treat infections
• trimethropim: antibacterial agent used in various preparations to treat infections
• warfarin and other drugs containing coumarin: blood-thinning agents used to prevent and treat heart and circulatory disorders.

Get more information about other diabetes oral antidiabetic drugs