Sulphonylureas

Introduction

The Sulphonylureas act mainly by augmenting insulin secretion and consequently are effective only when some residual pancreatic beta cells activity is present; during long term administration they also have extra-pancreatic actions. All may cause hypoglycemia but this is uncommon and usually indicates excessive dose. Followings are the common drugs;

1. Tolbutamide
2. Chlorprapamide
3. Glibenclamide
4. Glipizide


Mechanism of action

They bind with potassium channels on the cell membrane of beta cells and reduce the potassium permeability. Therefore cell membrane becomes depolarized. Thus calcium will influx to the cell. This will result insulin secretion.

Mode of actions

1. increase insulin secretion
2. increase peripheral sensitivity for insulin
3. extra-pancreatic functions are;

I. reduce hepatic glucose production
II. reverse post receptor defect in insulin action
III. increase number of insulin receptors

Pharmacokinetics

Oral absorption is good and it achieves peak plasma concentration within 2-4 hours after the ingestion. Sulphonylureas bind strongly with albumin therefore they implicate with other drugs which have an affinity towards albumin such as salicylate and sulfonamide. These drugs are excreted via urine therefore extra precautions should be taken when prescribing for a patient with renal failure. Sulphonylureas are contraindicated during pregnancy as they cross the placenta (except glibenclamide).

Adverse drug reactions

1. They cause hypoglycemia. This effect is highest with chlorprapamide and glibenclamide and lowest with tolbutamide.
2. They increase appetite therefore increases the weight gain.
3. 3% of patients experience gastrointestinal disturbances.
4. They can cause allergic skin reaction
5. Bone marrow suppression is a dreaded drawback of these drugs but it occurs rarely.

Drug interaction

1. following drugs can augment the hypoglycemic effect of Sulphonylureas by replacing them from albumin

I. Non-steroidal anti-inflammatory drugs(Diclofenac sodium)
II. Uricosuric drugs(Sulfinpyrazone)
III. Alcohol
IV. Mono Amine Oxidase inhibitors (Phenalzine)
V. Antibacterial agents (sulfonamide, trimethoprime, chloramphenicol)
VI. Antifungal agents (imidazole)

2. Following drugs reduce the effects of Sulphonylureas

I. Thiazide diuretics (HCT)
II. Corticosteroids

Clinical uses

1. Useful in early stages of type 2 diabetes mellitus
2. They can be combined with Metformin or Glitazones.
3. Sulphonylureas are given ½ hour prior to the meal
4. Glibenclamide should not be given to elderly patients and patients with renal failure.