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Agenda

  Agenda:

  1. TZDs Overview
  2. Pioglitazone and Diabetes
  3. Rosiglitazone and Diabetes
  4. Pioglitazone vs. Rosiglitazone
  5. TZDs Fracture Data
  6. TZDs and Cancer
  7. Summary.

 

  1. Pioglitazone [Actos] :  15/30/45 mg
  2. Rosiglitazone [Avandia]:  4mg/bid
  3. Troglitazone (Rezulin) : Withdrawn from the U.S market in 2000 due to hepatotoxicity.
  4. Action: Decrease in insulin resistance at peripheral sites and in the liver that results in increased insulin-dependent glucose disposal and decreased hepatic glucose output.
  5. Peak Concentration : 2 to 4 hours
  6. Initial Response :  4 weeks
  7. Selective binding at the  peroxisome proliferator activated receptor- gamma (PPAR-g),which is found in adipose tissue, skeletal muscle, pancreatic beta-cells, vascular endothelium ,macrophages and the liver.

 

  1. Troglitazone and Rosiglitazone : purely PPAR-g agonists
  2. Pioglitazone : some PPAR-a effects  expressed mostly in liver, heart, skeletal muscle and vascular walls.This may account for the different effects on lipids.
  3. Dual PPAR (a&g)agonists: Muraglitazar(FDA-approved ; Cardiac Safety?)
  4. Reported Adverse Effects:
    1.    Weight gain : dose-dependent and time-dependent

                                     fluid retention & proliferation of new adipocytes

    1.    Fluid retention : more prominent with concomitant insulin therapy

         PPAR-gamma stimulation of sodium reabsorption by the collecting tubule cells

   Decreased bone density,Hepatotoxicity ,Macular edema  and Eczema.