Core Drugs Of Diabetes Flashcards
What are 4 drugs used to treat diabetes?
Metformin
Dipeptidyl-peptidase 4 inhibitors (DPP-4) inhibitors
Sulphonylurea
Sodium glucose co-transporter inhibitors (SGLT2 inhibitors)
What is the mechanism of action of metformin?
Activates AMPK in hepatocyte mitochondria.
This inhibits ATP production
This blocks gluconeogenesis and subsequent glucose output
It also blocks adenylate Cyclase which promotes fat oxidation (breakdown)
Both of these help to restore insulin sensitivity
What is the drug target of metformin?
5’-AMP-activated protein kinase (AMPK)
In the hepatocyte mitochondria
What are the main side effects of metformin?
GI side effects in 20-30% of patients - abdominal pain, decreased appetite, diarrhoea, vomiting
Particularly present when high doses are given. Slow increases in dose may increase tolerability
What features of Metformin allow it to have its effects?
Highly polar (so can’t cross plasma membranes easily)
Requires organic cation transporter-1 (OCT-1) to access tissues
Explains why it can accumulate in the liver (therapeutic effects) and GI tract (side effects)
When is metformin most effective?
In the presence of endogenous insulin.
So when there are still some pancreatic beta islet cells working
What is an example of a DPP-4 inhibitor?
Sitagliptin
What is the mechanism of action of DPP-4 inhibitors?
Inhibitions the action of DPP-4, an enzyme present in vascular endothelium and can metabolism incretins in the plasma
Incretins (eg. GLP-1) are secreted By enteroendocrine cells and help stimulate the production of insulin when it’s needed (eg. After eating) and reduce the production of glucagon but the liver when it isn’t needed (eg. During digestion)
They also slow down digestion and decrease appetite
What is the drug target of DPP-4 inhibitors
DPP-4
On the vascular endothelial
What are the main side effects of DPP-4 inhibitors?
Upper respiratory tract infections (5% of patients)
Flu like symptoms (headache, runny nose, sore throat)
Less common: severe allergic reactions
Avoid in patients with pancreatitis
What is a pro of metformin and DPP-4 that other diabetes drugs don’t have?
They do not cause weight gain
When are DPP-4 Is most effective?
When there are some residual pancreting beta islets functioning and producing insulin
As they augment insulin secretion
What is an example of a sulphonylurea
Gliclazide
What is the mechanism of action of sulphonylurea?
Inhibits the ATP-sensitive potassium (KATP) 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 drug target of sulphonylurea?
ATP- sensitive potassium channel
In the pancreatic beta cell
What are the side effects of sulphonylurea?
Weight gain
Hypoglycaemia
When are sulphonylureas most effective?
They augment insulin secretion
So work best when there are still some functioning beta cells
(The weight gain caused by sulphonylurea can be counteracted by giving metformin too)
What is an example of an SGLT2 inhibitor?
Dapaflifozin
What is the mechanism of action of SGLT2 inhibitors?
Reversibly inhibits sodium glucose co-transporter -2 in the renal Proximal convoluted tubule
This reduces glucose reabsorbtion and increases urinary glucose secretion
What is the drug target of SGLT2 inhibitors?
Sodium glucose co-transporter 2
In the proximal convoluted tubules of the kidney
What are the side effects of SGLT2 inhibitors?
Uro genital infection due to increased glucose load
Slight decrease in bone formation
Can worsen diabetic ketoacidosis (stop immediately)
They also cause weight loss and a reduction in BP
When would SGLT2 inhibitors be less effective?
They rely on normal renal function
So in patients with renal impairment they would be less effective
