Pharmacology: Thiazolidinediones(TZDs)

Question 1

describe the molecular mechanism of TZDs

Answer 1

they are PPARgamma ligands, they bind to the PPARgamma gene and results in formation of complex with a co-activator

Question 2

what effect do TZDs have on the target PPARgamma genes

Answer 2

increase transcriptional activation

Question 3

how many target genes are there for TZDs

Answer 3

100s, some beneficial some adverse

Question 4

what type of cells do TZDs mainly effect

Answer 4

adipocytes

Question 5

what is the net result of TZDs activity

Answer 5

increased insulin sensitivity

Question 6

describe the effect of TZDs on adipocytes

Answer 6

increase differentiation from pre-adipocytes to adipocytes, increases subcutaneous fat mass, increases adiponectin

Question 7

describe the action of adiponectin

Answer 7

acts on liver to increase insulin sensitivity

Question 8

describe what the action of ‘lipid steal’ is as part of TZDs actions

Answer 8

when free fatty acid uptake removes fat from liver and muscle, reducing lipotoxicity

Question 9

what are TZDs also known as

Answer 9

glitazones

Question 10

how potent are TZDs

Answer 10

quite potent 15-20mmol/mol HbAC1 reduction, esp in obese women

Question 11

what effect to TZDs have on weight and why

Answer 11

weight gain(2-3kg), due to increase fat mass and fluid retention

Question 12

what effect to TZDs have on BP

Answer 12

lower it, SBP by around 4.7 and DBP by around 3.8

Question 13

what is the only available TZD, and what dose is used

Answer 13

pioglitazone, 15-30mg od

Question 14

what side effects may be seen with TZD use

Answer 14

weight gain, fluid retention(eg peripheral oedema), fracture risk

Question 15

why is there an increased fracture risk with TZD use

Answer 15

increased fat accumulation in bone marrow and decreased bone density

Question 16

describe where TZDs are used in T2DM treatment pathway

Answer 16

second line(after first line metformin)
used when compelling need to reduce hypoglycaemia or when cost is major issue(very cheap)