 ORAL HYPOGLYCEMIC AGENTS
Oral hypoglycemic agents are usually required in managing people with Type II diabetes, when diet and exercise alone fail to optimize the blood glucose levels. However, if the patient is very symptomatic, or if the blood glucose values are very high ( fasting levels around 250mg% or more), OHAs, alone or in combination with insulin, should be started along with diet and exercise from the start. Later when the blood glucose levels are under control, efforts can be made to reduce the OHA and/or insulin doses and see if the patient can be maintained with diet and exercise alone.
The use of OHAs should be as an addition to diet and exercise and not as a substitute.
- Pathophysiologic Basis of OHA Therapy
- Main Groups of OHAs
- OHA's: Special Aspects
- OHA's: Side effects
- When to start OHA therapy?
- Which OHA is the drug of choice?
- General guidelines when using OHAs :
- initiating therapy
- adjusting the dose
- review therapy if expected effect not seen
- maximum dose advisable
- Conditions which can interfere with the action of OHAs
- CLINICAL SCENARIOS :
- OHA Therapy in a non obese Type II patient: ALGORITHM
- OHA Therapy in an Obese Type II patient: ALGORITHM
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- Contra-Indications for the use of OHAs
- OHA Failure
- Drug interactions
- Use of Fixed dose OHA combinations
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Pathophysiologic Basis of OHA Therapy
Until a few years back, the types of OHAs available for use was limited. In recent times, a number of new molecules have come into the market and their correct use must be based on an understanding of their mode of action.
Thus it becomes essential to understand the pathophysiology leading to hyperglycemia. Individual characteristics also play a role whilst choosing the best OHA for a person with diabetes. Type II diabetes is characterized by three basic abnormalities that contribute to the development of hyperglycemia:
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Impaired insulin secretion by the pancreas
Excessive glucose production by the liver
Peripheral insulin resistance mainly in the skeletal muscle.
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Main Groups of OHAs
Sulfonylureas
Sulfonylureas work primarily by stimulating pancreatic insulin secretion, which in turn reduces hepatic glucose output and increases peripheral glucose disposal.
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The sulfonylureas are often classified as belonging to the first or second generation.
The First generation sulfonylureas:
- Acetohexamide
- Chlorpropamide
- Tolazamide
- Tolbutamide.
The second generation sulfonylureas are:
- Glibenclamide
- Glyburide
- Glipizide
- Glicazide
- Glimepiride
The first generation sulfonylureas are rarely used now.
Biguanides
Two drugs in this category are phenformin and metformin.
Biguanides work mainly by
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Suppressing excessive hepatic glucose production
- Increasing glucose utilization in peripheral tissues to a lesser degree.
- Possibly reduce food intake and thus reduce intestinal glucose absorption
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As the biguanides do not stimulate endogenous insulin secretion, hypoglycemia does not occur when they are used alone and therefore they are sometimes called anti-hyperglycemic agents rather hypoglycemic agents.
The use of phenformin has decreased considerably and it is usually metformin that is now used when a biguanide is prescribed.
Alpha-Glucosidase Inhibitors
Acarbose is an alpha-glucosidase inhibitor that slows down the breakdown of disaccharides and polysaccharides and other complex carbohydrates into monosaccharides. The enzymatic generation and subsequent absorption of glucose is delayed and the postfood blood glucose values, which are characteristically high in patients with type II diabetes, are reduced.
Meglitinides
A very recent addition to the OHA group. It is a ultra short acting drug which acts directly on the the beta cells of the pancreas and increases the secretion of insulin. It also corrects the problems with the pulsatile release of insulin which is seen in Type II diabetes.
Thiazolinediones
Thiazolidinediones are a new class of oral antidiabetic agents (commercially known as glitazones) that enhance insulin sensitivity in peripheral tissues. Troglitazone was the first glitazone introduced to the market, and though widely used, it has now been withdrawn from the market as its use has been linked with hepatocellular injury and death secondary to liver failure.
Rosiglitazone and Pioglitazone are now available for clinical use and are extremely potent in reducing peripheral insulin resistance.
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