Management Of Type 2 Diabetes Flashcards
Why is Metformin usually first choice?
Improves outcome
Well tolerated
Cheap
Wheat are the defects in T2DM?
Beta cell dysfunction
Diminished incretin effect
Excess glucagon
Insulin resistance
Where does Metformin mainly work?
The liver and muscles
What type of drug is Metformin?
Biguanide
What does Metformin do?
Improve insulin sensitivity
How does Metformin improve insulin sensitivity?
Affects glucose production, decrease fatty acid synthesis
Improve receptor function
Inhibit gluconeogenic pathways
What is Metformin half life?
6 hours
What are the advantages of Metformin?
Improves CV outcomes and mortality in obese T2DM
Efficacious
Well tolerated
Not associated with weight gain
HbA1c 12-17% reduction
Used in pregnancy
Cheap
What are disadvantages of Metformin?
GI side effect
Risk of lactic acidosis by inhibiting lactic acid uptake by liver
-hypoxia
-renal failure
-hepatic failure
-alcohol abuse
Risk vit B12 malabsorption
What are sulphonylureas?
The gli…ides - glimepiride, gliclazide, glipizide
When to use sulphonylureas?
If osmotic symptoms or HbA1c increase rapidly titration based on home blood glucose monitoring
What does sulphonylureas do?
Increase insulin release
Where does sulphonylureas act?
On the pancreas
What is the mechanism of action of sulphonylureas?
Bind to sulfonylurea receptors (SUR-1) on functioning pancreatic beta cells
Binding closes the linked ATP- sensitive potassium channel
Decreased potassium influx depolarisation of the beta cell membrane
Voltage- dependent calcium channels open and result in an influx of calcium
Translocation and exocytosis of secretory granule of insulin to the cell surface
What are the advantages of sulfonylurea?
Rapid improvement of control
Rapid improvement if symptoms
Rapid titration
Cheap
Generally well tolerated
What a re the disadvantages of sulfonylurea/
Hypoglycaemia risk
Weight gain
Caution in renal and hepatic disease
CI in pregnancy and breast feeding
SE
-hypersensitivity and photosensitive reactions
-blood disorders
What are thiazolidinediones?
The …glitazones
What do thiazolidinedones do?
Improve insulin action
What do glitazones act on?
Muscle, liver and adipose tissue
What is a thiazolidinediones?
Pioglitazone
What is the mechanism of pioglitazone?
Selectively stimulates the nuclear receptor peroxisomes proliferator- activated receptor gamma and the a lesser extent PPAR-alpha
Modulates the transcription of insulin sensitive genes involved in the control of glucose and lipid metabolism in the muscle, adipose tissue and the liver
What does pioglitazone cause?
Reduce insulin resistance in the liver and peripheral tissues
Increase the expense of insulin dependent glucose
Decrease the withdrawal of glucose from liver
Reduce quantity of glucose, insulin and glycogen Haemoglobin in the bloodstream