True about pioglitazone are all except (AIIMS May 2011)
|A||Metabolized in the liver by CYP3A4.|
|B||Selective agonist for the nuclear peroxisome proliferator tor activated receptor gamma|
|C||It causes transcription of gene for carbohydrate and fat metabolism in the absence of insulin|
|D||It should be avoided in a patient with cardio- vascular disease|
(Ref. : Goodman and Gilman 12th /1260, Katzung 11th /742-743)
a. Thiazolidinediones require the presence of insulin for pharmacological activity and are not indicated to treat type 1 diabetes.
b. Thiazolidinediones (glitazones) sensitize peripheral tissues to insulin. They bind a nuclear receptor called peroxiSOOI proliferator-activated receptor gamma (PP AR-gamma) and affect the expression of a number of genes.
c. Two drugs of this class, rosiglitazone and pioglitazone are available for clinical use. Rosiglitazone is metabolized by the CYP 2C8 isoenzyme and pioglitazone is metabolized by CYP 2C8 and CYP 3A4.
d. Edema occurs in about 3-4 % of patients receiving monotherapy with rosiglitazone or pioglitazone. The edema occrs more frequently (10-15 %) in patients receiving concomitant insulin therapy and may result in congestive heart failure. The drugs are contraindicated in diabetic individuals with New York Heart Association class III and IV cardiac status.