Diabetes Flashcards
(24 cards)
What is the primary mechanism of action of metformin?
activates AMPK in hepatocyte mitochondria
this inhibits ATP production
this blocks gluconeogenesis and subsequent glucose output
Blocks adenylate cyclase which promotes fat oxidation
this restores insulin sensitivity
What is the drug target of metformin?
5-AMP-activated protein kinase - AMPK
primary site of metformin action is the hepatocyte mitochondria
What are the side effects of metformin?
Abdominal pain
Decreased appetite
Diarrhoea
Vomiting
When is metformin most effective?
Presence of endogenous insulin so is most effective with some residual functioning pancreatic islet cells
What transporter does metformin require to access tissues?
OCT-1, so it can accumulate in liver (therapeutic effect) and gastrointestinal tract (side effect)
What is an example of dipeptidyl-peptidase 4 inhibitor?
Sitagliptin
What class of drugs does sitagliptin belong to?
DPP-4 inhibitor
What is the primary mechanism of action of DPP4 inhibitors?
Inhibit DPP4
What is DPP-4?
An enzyme present in vascular endothelium and can metabolise incretins in the plasma. Incretins are secreted by enteroendocrine cells and help stimulate the production of insulin, and reduce the production of glucagon by the liver when it is not needed.
What are incretins?
Incretins are secreted by enteroendocrine cells and help stimulate the production of insulin, and reduce the production of glucagon by the liver when it is not needed.
What is an example of an incretin?
GLP-1
What is the primary site of DPP4 inhibitor action?
The vascular endothelium - where DPP4 is located
What are the side effects of DPP4 inhibitors?
Upper respiratory tract infection Flu like symptoms Headache Runny nose Sore throat
Why isn’t sitagliptin administered to patients with pancreatitis?
It’s associated with a higher risk of pancreatitis
Give an example of a sulphonylurea
Gliclazide
What is the primary mechanism of action of sulphonylurea?
Inhibits the ATP-sensitive potassium channel on the pancreatic beta cell
This channel controls beta cell membrane potential.
inhibition causes depolarisation
which stimulates Ca2+ influx
and subsequent insulin vesicle exocytosis
What is the primary site of action of sulphonylureas?
Pancreatic beta cells - ATP sensitive potassium channel
What are side effects of sulphonylurea?
Hypoglycaemia
Weight gain
How to mitigate weight gain when administering sulphonylurea?
Concurrently administer with metformin
Give an example of sodium glucose co transporter inhibitors (SGLT2)
Dapaglifozin
What is the primary mechanism of action of SGLT2 inhibitors?
Reversibly inhibits sodium glucose co transporter 2 in the renal proximal convoluted tubule
to reduce glucose reabsorption and
increase urinary glucose excretion
What is the drug site of SGLT2 inhibitor action?
SGLT2 on the proximal convoluted tubule
What are the side effects of SGLT2?
Urogenital infections Decrease in bone formation Worsens diabetic ketoacidosis Weight loss Blood pressure reduction
Which drug class used to treat diabetes is less effective in patient with renal impairment?
SGLT2 inhibitor
