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                         Drug action

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Drug action in diabetes

         

Pancreas, the center of insulin production 

 

Sugar metabolism and pancreas.

On consumption of food including sugars, the insulin secretion is triggered on from pancreas to titrate the blood sugar levels at constant levels with in a narrow range. A deficiency of insulin secretion and / or resistance to action of secreted insulin leads to increased blood sugar levels, in response to meals and also in fasting state. In a patient of diabetes both insulin resistance and defects of insulin release are present to varying degree.

 

One can intervene at various levels to control blood sugar levels in a patient of diabetes.

 

1. Decrease load on Pancreas

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Diet control

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Exercise.

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Inhibitors of Carbohydrate digestion.

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Inhibitors of Carbohydrate absorption.

 

2. Increasing Insulin secretion from Pancreas

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Secretagogues

3. Increase Insulin action.  (Insulin sanitizers.)

4. Decreasing production of glucose (gluconeogenesis) by the liver.

5. Increasing peripheral utilization of glucose by muscle, adipose tissue (fat

    tissue).

 

 

Intervention for diabetic control

 

 Decrease load on pancreas.

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This is the most crucial step in management. Taking off the load of sugar metabolism from pancreas means, less secretion of insulin is required by failing pancreas .This can be achieved by:

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Dietary restriction of sugars in any form. Limiting total calorie intake to desired levels.   

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Certain drugs (Inhibitors of Carbohydrate digestion or absorption) when taken with major meals prevent sugar absorption to certain extent, and /or delay the absorption of sugars from intestine to blood stream, thereby putting less load on pancreas at any given time. These drugs can be safely combined with all other medication .                                     

 

Mechanism of Drug action.

 

Inhibitors of Carbohydrate digestion or absorption.

  1. Inhibitors of Carbohydrate digestion.

       (Alpha Glucosidase Inhibitors.)

  1. These agents can slow the rate of glucose breakdown and hence absorption and thus reduce post Prandial excursions of hyperglycemia.

  2. These agents inhibit or block digestive enzymes of carbohydrate in brush border of intestine, thereby delaying break down of carbohydrates

  3. The effect of these agents (Acarbose, Miglitol, Voglibose) is enhanced by good dietary compliance and by consumption of the drug with meals.

  1. Inhibitors of Carbohydrate absorption.

        (Non digestible plant fibers.)

  1. Non digestible plant fibers entrap carbohydrate within their matrix. This reduces the rate of carbohydrate digestion and impedes interaction of carbohydrate with digestive enzymes of brush border.

  2. They reduce post Prandial hyperglycemia

  1. Insulin analogues. (providing insulin derivatives from outside)

  2. Gene therapy.

  3. Insulin delivery routes. (insulin delivery via nasal, oral mucosa; small intestine and rectum; as an aerosol spray.)

  4. Insulin Secretagogues. (drugs stimulating insulin secretion by pancreas)

 

 

Insulin Secretagogues
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act by stimulating beta cells of pancreas to release insulin.

 

Sulfonylureas 

  1. Second generation Sulfonylureas 

  1. Glibenclamide

  2. Glipizide

  3. Gliclazide

  1. Third generation Sulfonylureas 

  1. Glimiriperide

  1. Meglitinides

  1. Repaglinide

  2. Netiglinide

 

Increase Insulin action.

 

 

Insulin sensitizers.

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Newer group of medicines which act by increasing sensitivity to insulin.

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These are crucial as insulin resistance is a major contributor in NIDDM (non insulin dependent diabetes mellitus)

 

Classification of Insulin sensitizers.

 

Biguanides

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Decrease blood sugar levels by two mechanisms.

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act on liver to reduce glucose production.

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act as insulin sensitizer, and thus increased insulin action in peripheral tissues like muscle, fat and liver.

 

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Metformin

 

Thiazolidinediones

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Newer class of drugs which act as insulin sensitizer.

 

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Rosiglitazone.

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Pioglitazone.

 

Secretagogues with Insulin sensitizing effect.

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Glimiperide.

 

                                    Glucose metabolism & interventions

                                                                          Dietary Carbohydrate.

                                                                           

                                               Digestion.      Alpha Glucosidase Inhibitors

                                                                  

                                                      Absorption       Dietary fiber supplement     

                                                            

                                                     Blood glucose.

                                                                 

                                                   Insulin secretion.   Insulin Secretagogues.

                                                                           

                                            Insulin action.    Insulin senitizer or potentiators.

                                   

                                                                                         

                                    Increased Glucose utilization.      Decreased Hepatic( liver) glucose output.

      

                                                                               

                               

                                                Insulin analogues.

 

 Mechanism of Drug action in controlling Hyperglycemia 

                                

                                                        (High blood sugar)

                                                        

                                                                            

                                                                           Stomach

                                                    Delays carbohydrate absorption

                                                (Acarbose-Alpha Glucosidase Inhibitors.)

                                                   

                                                                              

                                            Reduced hyperglycemia        

                               Liver                                                                              Pancreas             

                                                             

                                                                                                             

      Reduce excessive hepatic glucose output                                  Stimulates impaired insulin secretion 

           (Metformin, Thiazolidinediones)                                           (Sulfonylureas)                                             

                                                                         

                                                 Peripheral tissues like Muscles

                       Reduce peripheral insulin resistance with better utilization of glucose by muscles etc.

                                                  (Metformin, Thiazolidinediones) 

 

 

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