Pharm - Diabetets Flashcards
What are the 4 classes of diabetes drugs?
Metformin
Dipeptidyl-peptidase 4 inhibitors
Sulphonylurea
Sodium-glucose co-transporter inhibitors
What is the primary effect of metformin?
- Inactivates AMPK in hepatocyte mitochondria
- Stops ATP production
- Blocks gluconeogenesis and HGO
- Blocks adenylate cyclase which promotes fat oxidation
- Therefore restores insulin sensitivity
Where is the target for metformin?
5’-AMPK activated protein kinase
Where does metformin act?
Hepatocyte mitchondria
What are the main side effects of metformin?
GI:
- Abdominal pain
- Decreased appetite
- Diarrhoea
- Vomiting
How common are metformin side effects?
20-30% of patients
What affects tolerability of metformin?
When a slow increase in dose is given there is better tolerability - a very high dose causes side effects
What explains metformin accumulating in the liver and GIT?
Metformin is highly polar and requires organic cation transporter 1 (OCT-1) to access tissues
When is metformin most effective?
In the presence of endogenous insulin therefore in residual functioning pancreatic islet cells
What is an example of a DPP-4 inhibitor?
Sitagliptin
What is the primary effect of DPP-4 inhibitors?
Inhibit DPP4
What does DPP-4 do?
Metabolises incretins in the plasma
What do incretins e.g. GLP-1 do?
- Secreted by enterendocrine cells and help stimulate the production of insulin when it is needed
- Reduce production of glucagon by the liver when it is not needed
- Slow down digestion and decrease appetite
What is the target for DPP4 inhibitors?
DPP-4
Where is the effect of DPP4 inhibitors?
DPP-4 is found in the vascular endothelium
What are the common side effects of DPP4 inhibitors?
Upper respiratory tract infections Flu-like symptoms: -Runny nose -Sore throat -Headache
What are the uncommon effects of DPP4 inhibitors?
Serious allergic reactions - avoid in patients with pancreatitis
DPP4 = Don’t with Pancreatitis Patients
Do DPP4 inhibitors cause weight gain?
No
(DPP = Doesn’t Pig People)??
When are DPP4 inhibitors only really effective?
When some residual pancreatic beta-cell activity is present, as they work by augmenting insulin production
What is an example of sulphonylurea?
Gliclazide
What is the primary effect of sulphonylurea?
Inhibits ATP sensitive potassium channel (KATP)
What is the role of KATP?
Controls beta cell membrane potential - therefore sulphonylurea causes depolarisation stimulating calcium ion influx to beta cells and thus insulin vesicle exocytosis
What is the target of sulphonylurea?
ATP- sensitive potassium channel
Where does sulphonylurea act?
Pancreatic beta cells
What are the side effects of sulphonylurea?
Weight gain
Hypoglycaemia
When are sulphonylureas only really active?
When some residual pancreatic beta-cell activity is present, as they work by augmenting insulin production
How do we mitigate weight gain from sulphonylurea?
Concurrent administration with metformin
What is an example of SGLT2 inhibitors?
Dapaglizofin
What is the primary effect of SGLT2 inhibitors?
Reversibly inhibits SGLT-2 in the kidney to reduce glucose reabsorption and increase its excretion in the urine
What is the target of SGLT2 inhibitors?
SGLT-2
Where is the effect of SGLT2 inhibitors?
Renal proximal convoluted tubule
What are the side effects of SGLT2 inhibitors?
Uro-genital infections due to increased glucose load
Slight decrease in bone formation
What can be worsened by SGLT2 inhibitors?
Diabetic ketoacidosis
What can SGLT2 inhibitors cause?
Weight loss and reduction in blood pressure
What influences SGLT2 inhibitors?
Normal renal function is needed for SGLT-2 action therefore less effective in patients with renal impairment
