Diabetes Flashcards
Metformin mechanism
Increased insulin receptor sensitivity-more uptake from fat and muscle Inhibits hepatic gluconeogenesis Decreased glucose uptake from gut No action on beta cells Reduces HbA1c by 2%
Metformin
Biguanide
Metformin pharmacokinetics
Half life 4 hours
2 or 3 times daily dosing
Not metabolised
Total renal elimination
Metformin ADRs
GI symptoms
Potential for lactic acidosis
Not in renal, hepatic or respiratory failure
B12 deficiency
Gliclazide
Sulphonylurea
Half life 10-12 hours
Glimepiride
Sulphonylurea
Half life 18-24 hours
Glipizide
Sulphonylurea
Sulphonylureas mechanism
Stimulation of beta cells - closes potassium channel, causing depolarisation, calcium influx and insulin granule secretion.
Reduce HbA1c 1-2%
Sulphonylureas ADRs
Hypoglycaemia Weight gain (more insulin)
Repaglinide
Meglitinide
Nateglinide
Meglitinides
Meglitinides mechanism
Similar to Sulphonylureas but distinct binding site on potassium channel
Shorter half life so given before meals
Pioglitazone
Thiazolidinediones
Thiazolidinediones mechanism
Insulin sensitisers
Via nuclear peroxisome stimulation
Suppresses gluconeogenesis in liver
Reduce HbA1c 1-1.5%
Thiazolidinediones ADRs
Weight gain and oedema Fractures in post menopausal women Bladder cancers Increase LDLs and HDLs Use contraindicated in heart failure
GLP 1 mechanism
More insulin secretion from beta cells
Promotes satiety in brain.
Reduced hepatic glucose output
Slowed gastric emptying
Acarbose
Alpha glucosidase inhibitor.
Acarbose mechanism
Delayed glucose load into blood (overall absorption not affected)
Drug is excreted unchanged
Acarbose ADRs
Flatulence and diarrhoea
Increased AST at high doses
SGLT2 inhibitor mechanism
Glucose not re absorbed, excreted in urine.
SGLT2 inhibitor ADRs
Thrush
UTI
Dapagliflozin
SGLT2 inhibitor
Canaglifozin
SGLT2 inhibitor
Thiazolidinediones metabolism
Via liver
T1/2 around 7 hrs
99% protein bound
Tolbutamide
Sulphonylurea
DPP4 inhibitors
GLP1 is broken down by DPP4, so this increases the half life
