Diabetes Flashcards
What are the four main classes of drugs used to treat Diabetes?
Metformin
DPP-4 Inhibitor
Suphonylurea
SGLT-2 Inhibitor
Describe the mechanism of action for Metformin
Activates AMP Kinase which blcoks ATP production
hence gluconeogenesis is inhibited
Also Inhibits Adenylate cyclase which promotes fat oxidation
What is the drug target of Metformin?
5’ - AMP activated protein Kinase = ENZYME DRUG TARGET
Where is the drug target of Metformin located?
hepatocyte mitochondria
what are the side effects of Metformin?
GI Side effects = Abdo pain, nausea, diarrhoea, vomiting
Why does metformin accumulate in the liver and the GI Tract?
The drug is highly polar and requires organic cation transporter-1 to access tissues
What is the main example of a DPP4 Inhibitor?
Sitagliptin
Describe the mechanism of action of Sitagliptin
Work by inhibiting the action of DPP-4.
This enzyme is present in vascular endothelium and can metabolise incretins in the plasma.
Therefore more incretins present, so more insulin produced
What is the drug target of sitagliptin and where is this target found?
DPP-4, found in the vascular endothelium
What are the side effects of Sitagliptin?
Upper respiratory tract infections
Flu-like symptoms
Serious allergic reactions
Why might sitagliptin be chosen over other Diabetes drugs?
Unlike others, doesn’t cause weight gain
What does sitagliptin need to be effective?
Since it works by augmenting insulin secretion, they are therefore only effective when some residual beta cell activity is present
What is the mechanism of action for sulphonylurea?
Inhibit 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 an example of a sulphonlyurea?
Gliclazide
What is the drug target of Gliclazide and where is it found?
ATP sensitive K+ channels
In the pancreatic beta cells
