Diabetes Flashcards
Primary mech. of metformin
activates AMPK in hepatocyte mitochondria to inhibit ATP
blocks gluconeogenesis (and more glucose output)
blocks adenylate cyclase to help fat oxidation
= help restore insulin sensitivity
Metformin drug targets?
AMPK (5’- Activated protein kinase)
in hepatocyte mitochondria
Metformin side effects
GI (20-30% of patients)
Abdominal pain, low appetite, diarrhoea, vomiting)
esp in high doses
slowly increasing dose can help improve tolerability instead
How does metformin have therapeutic and side effects? (3 marks)
accumulates in liver (therapeutic) and in GI tract (side effect) as it needs organic-cation-transporter1 (OCT-1) to access tissues because its v polar (3 marks)
examples of DPP-4 inhibitors
Dipeptide Peptidase 4 inhibitors
=Sitagliptin
Prim mech of DPP-4 inhibitors?
inhibit DPP-4
present in vascular endothelium and metabolises incretins in plasma
basically stops incretic metabolism
what do incretins do
Incretins (e.g. GLP-1) are secreted by enteroendocrine cells and help stimulate the production of insulin when it is needed (e.g. after eating) and reduce the production of glucagon by the liver when it is not needed (e.g. during digestion). Incretins also slow down digestion and decrease appetite.
sitaglipin drug target
DPP-4 inhibitor
mainly in vascular endothelium
examples of sulphonylurea
Glicazide
Prim mech of sulphonylurea
inhibit KATP channel on pancreatic beta cells, causes depolarisation and Ca2+ influx causes insulin vesicle exocytosis
what does the KATP channel do?
the ATP-sensitive potassium (KATP) channel on the pancreatic beta cell. This channel controls beta cell membrane potential
Drug target of sulphonylurea
KATP channel in pancreatic beta cells
Glicazide side effects?
weight gain
hypoglycemia
When are sulphonylureas most effective?
The sulfonylureas act mainly by augmenting insulin secretion and consequently are effective only when some residual pancreatic beta-cell activity is present.
SGLT2 inhibitor example and full form?
Sodium-glucose co-transporter (SGLT2) inhibitors
Dapaglifozin