False about pioglitazone aEUR'
It acts on insulin gene and even in absence of insulin helps in metabolism of carbohydrate km * Pioglitazone belongs to Thiazolidinediones -Other drugs of this group are Troglitazone, Rosiglitazone It is an oral antihyperglycemic agent that acts primarily by decreasing insulin resistance. - Pioglitazone deceases insulin resistance in the muscles, adipose tissues and in the liver resulting in increased L insulin dependent glucose disposal and decreased hepatic glucose output. Mechanism of action Pioglitazone is a potent and higly selective agonist for peroxisome proliferator activated receptor gamma (PPAR - PPAR receptors are, found in tissues impoant. for insulin action such as adipose tissue, skeletal muscle and liver. - PPAR is .found in highest level in adipose tissue. - Activation of PPAR7 nuclear receptors modulates the transcription of a number of insulin responsive genes involved in the control of glucose and lipid metabolism. -Pioglitazone appears to reduce insulin resistance by enhancing fatty acids storage and possibly by increasing adinopectin levels. - In animal models of diabetes pioglitazone reduces the hyperglycemia, hyperinsulinemia and hyperiglyceridemia which are characteristic of insulin resistant states. Pioglitazone depends on the presence of insulin for its mechanism of action. - Since piogletazone acts by enhancing the effect of circulating insulin it does not lower blood glucose in persons that lack endogenous insulin, - Circulating insulin level decrease with the use of pioglitazone indicating decrease in insulin resistance. Thiazolidinediones are considered euglycemics. -The overall response is similar to sulfonylureas and biguanide monotherapy. - Because their mechanism of action involves gene regulation, the thiazolidinediones have a slow onset and offset of activity over weeks or even months. - Combination therapy with sulfonylurea or insulin may lead to hypoglycemia. Metabolism of Pioglitazone Pioglitazone is extensively metabolized in liver by hydroxylation and oxidation. aiims pgmee answers & explanations - May 2011 Multiple CYP isoforms are involved in the metabolism of pioglitazone. - The cytochromes p450 isoforms primarily invove are : -CYP2 C8 - CYP 3A4 (to a lesser degree) Liver function should be monitored in patients receiving thiazolidinediones even though pioglitazone and rosiglitazone rarely have been associated with hepatotoxicity. Originally three member of thiazolidinedione family were introduced - Pioglitazone - Rosiglitazone - Troglitazone (This was withdrawn from the market due to an increase incidence of drug induced hepatitis). The withdraw! of troglitazone has also led to concerns of other thiazolidinediones also increasing the incidence of hepatitis and potential liver failure. Because of this FDA, recommends two to three months checks of liver enzyme for the first year of thiazolidinedione therapy, to check for this rare but potentially catastrophic complication. - Till date newer thiazolidinediones have been free of this problem. Thiazolidinediones should not be used in patients with NewYork Hea association class III or IV failure. The main side effect of all thiazolidinediones is water retention leading to edema.Sometimes there is significant water retention leading to decompensation of potentially previously unrecognized hea failure. herefore thiazolidinediones should be prescribed with both caution and patient warnings about the potential ,for water retention/weight gain especially in patients with decreased ventricular function.
It PPARy agonist
>It metabolized in liver
>Not given in case of diastolic dysfunction
It acts on insulin gene and even in absence of insulin helps in metabolism of carbohydrate