Sulphonylureas Flashcards
Indications
Type 2 diabetes mellitus: As a single agent to control blood glucose and reduce complications where metformin is contraindicated or not tolerated. In combination with metformin (and/or other hypoglycaemic agents) where blood glucose is not adequately controlled on a single agent.
Mechanisms of action
Sulphonylureas lower blood glucose by stimulating pancreatic insulin secretion. They block ATP-dependent K+ channels in pancreatic β-cell membranes, causing depolarisation of the cell membrane and opening of voltage-gated Ca2+ channels. This increases intracellular Ca2+ concentrations, stimulating insulin secretion. Sulphonylureas are only effective in patients with residual pancreatic function. As insulin is an anabolic hormone, stimulation of insulin secretion by sulphonylureas is associated with weight gain. Weight gain increases insulin resistance and can worsen diabetes mellitus in the long term.
Adverse effects
Dose-related side effects such as gastrointestinal upset (nausea, vomiting, diarrhoea, constipation) are usually mild and infrequent. Hypoglycaemia is a potentially serious adverse effect, which is more likely with high treatment doses, where drug metabolism is reduced (see Warnings) or where other hypoglycaemic medications are prescribed (see Important interactions). Sulphonylurea-induced hypoglycaemia may last for many hours and, if severe, should be managed in hospital. Rare hypersensitivity reactions include hepatic toxicity (e.g. cholestatic jaundice), drug hypersensitivity syndrome (rash, fever, internal organ involvement) and haematological abnormalities (e.g. agranulocytosis).
Warnings
Gliclazide is metabolised in the liver and has a plasma half-life of 10–12 hours. Unchanged drug and metabolites are excreted in the urine. A dose reduction may therefore be required in patients with hepatic impairment and blood glucose should be monitored carefully in patients with renal impairment. Sulphonylureas should be prescribed with caution for people at increased risk of hypoglycaemia, including those with hepatic impairment (reduced gluconeogenesis), malnutrition, adrenal or pituitary insufficiency (lack of counter-regulatory hormones) and the elderly.
Interactions
Risk of hypoglycaemia is increased by co-prescription of other antidiabetic drugs including metformin, thiazolidinediones (e.g. pioglitazone) and insulin. The efficacy of sulphonylureas is reduced by drugs that elevate blood glucose, e.g. prednisolone, thiazide and loop diuretics.
Prescription
There are several sulphonylureas to choose from. Those with a shorter duration of action and hepatic metabolism (e.g. gliclazide) are the easiest to use, particularly in elderly patients with impaired renal function. Sulphonylureas are prescribed for oral administration only.
Administration
Sulphonylureas should be taken with meals (e.g. once daily at breakfast or twice daily at breakfast and evening meal).
Communication
Advise patients that a sulphonylurea has been prescribed to control the blood sugar level and reduce the risk of diabetic complications, such as heart attacks. Explain that tablets are not a replacement for lifestyle measures and should be taken in addition to a calorie-controlled diet and regular exercise. Warn them about hypoglycaemia, advising them to watch out for symptoms, such as dizziness, nausea, sweating and confusion. If hypoglycaemia develops, they should take something sugary (e.g. glucose tablets or a sugary drink) then something starchy (e.g. a sandwich), and seek medical advice if symptoms recur.
Monitoring
Assess blood glucose control by measuring glycated haemoglobin (HbA1c) (target <58 mmol/mol). Blood glucose monitoring is not routinely required, although measurement may be helpful to determine if any unusual symptoms are due to hypoglycaemia. Measurement of renal and hepatic function before treatment can determine need for caution or identify contraindications to treatment.
