drug notes: thiazolidinesdiones Flashcards
what type of agonists are thiazolidinediones?
-are PPARgamma agonists
what is PPARgamma?
-a transcription factor
what do thiazolidinediones have to do with PPAR gamma ?
Activate PPAR-gamma receptor in adipocytes to promote adipogenesis and fatty acid uptake
- thiazolidinediones are agonists/ligands which bind to and activate PPARgamma
- ligand activation results in recruitment of coactivators
- there then is an increased transcriptional activation of PPARgamma target genes
- activation of PPARgamma causes insulin sensitization and glucose metabolism
what do TZDs mainly affect?
adipose tissue
what affect do TDZs have on adipose?
- increase differentiation from pre adipocytes to adipocytes
- increases fat mass (subcutaneous
- ‘lipid steal’ (FFA uptake removes fat from liver and muscle which reduces lipotoxicity)
- increases adinoponectin which acts on liver to increase insulin sensitivity
NET RESULT= INCREASED INSULIN SENSITIVTY
whats another name for thiazolidinediones?
glitazones
in summary- what do TZDs do?
Activate PPAR-gamma receptor in adipocytes to promote adipogenesis and fatty acid uptake
- they are PPARgamma agonists which switch on 100s of genes
- their net effect is to increase fat mass in subcutaneous depots and to ‘suck out’ fat from viscera (liver, pancreas) and muscle
- also increased adiponectin and reduced ‘inflammatory cytokines’ like TNFalpha and IL-6
what effects do TDZs have on weight?
they increase weight
what effects do TDZs have on blood pressure?
reduce blood pressure
what is the only available TDZ?
pioglitazone
what are side effects of TDZs?
- weight gain (usually 2-3kg)
- fluid retention
- fracture risk
effect of TDZs on CV risk?
-reduces risk of CVD!!
when are TDZs used?
-2nd line to metformin when either cost is a major issue or there is a need to minimise hypoglycaemia
