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Thiazolidinediones

An agonist of peroxisome proliferator activated receptors (PPARs), primarily gamma receptors, in the cell nucleus.

Thiazolidinediones are peroxisome proliferator-activated receptor gamma activators that enhance insulin sensitivity in peripheral tissues and reduce hepatic glucose production.

Thiazolidinediones, agonists of PPAR-gamma reduce hyperglycemia via enhanced fatty acid uptake by adipose tissue and improved beta-cell function and insulin sensitivity.

Achieves hypoglycemia through enhanced insulin stimulated glucose uptake.

They augment insulin signaling, leading to metabolic overload, and expose the myocytes to the delirious effects of glucoselipo toxicity.

Peroxisome proliferator-activated receptors (PPARs) regulate genes involved in lipid and energy metabolism.

Ligand activated nuclear transcription factors activate transcription genes that alter glucose and lipid metabolism.

Decrease blood glucose by reducing insulin resistance and improve peripheral glucose disposal.

Improves blood pressure, vascular reactivity and fibrinolysis seen in insulin resistance syndrome.

When used as monotherapy, especially at high dose, associated with weight gain.

Associated with fluid retention.

Thiazolidinediones (TZDs), which are peroxisome proliferator-activated receptor (PPAR)-gamma agonists, can cause dose-related fluid retention, particularly when used in combination with insulin. 

Decreases glycated hemoglobin levels by an average of about 1% point or less and increases body weight, adverse effects on lipids, fluid retention and anemia.

Include agents pioglitazone (Actos) and rosiglitazone (Avandia) which decrease blood glucose by reducing insulin resistance and improve peripheral glucose disposal.

Pioglitazone and rosiglitazone reduce inflammatory markers.

Pioglitazone produces greater increases in HDL and reduces triglycerides to a greater degree than rosiglitazone.

May act to slow beta cell failure.

May be associated with increased risk of cardiovascular events, such as congestive heart failure, acute myocardial infarction, and mortality when compared to other oral hypoglycemic agents.

Fluid retention may lead to or exacerbate heart failure. 

Patients treated with insulin, including Afrezza, and a PPAR-gamma agonist should be observed for signs and symptoms of heart failure. 

If heart failure develops, it should be managed according to current standards of care, and discontinuation or dose reduction of the PPAR-gamma agonist must be considered.

Not recommended for use in patients with a history of congestive heart failure.

Recommended as second and third line treatments in combination with other oral agents or insulin to achieve glycemic control.

Associated wiyh increased frequency of bone fractures, edema, heart failure and increaded risk of bldder cancer,

PPAR-gamma receptors are expressed in endothelial, renal, and retinal vessels.

Thiazolidinediones induce peripheral and pulmonary edema due to vasodilation, sodium reabsorption in the kidney and as direct effects on vascular endothelia; permeability.

May be an association with diabetic macular edema (Idris I et al).

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