Pharmacology of Diabetes Flashcards
What are 4 drugs used in the treatment of diabets?
- Metformin
- DPP-4 inhibitors
- Sulphonylureas
- SGLT-2 inhibitors
What is the principle drug target for Metformin?
AMP activated protein kinase
What is the principle drug target for DPP-4 inhibitors?
Dipeptidyl peptidase-4 (DPP-4)
What is the principle drug target for Sulphonylureas?
ATP-sensitive K+ channels
What is the principle drug target for SGLT-2 inhibitors?
Sodium-glucose co-transporter-2
What is the drug target type for Metformin?
Enzyme
What is the drug target type for DPP-4 inhibitors?
Enzyme
What is the drug target type for Sulphonylureas?
Ion channels
What is the drug target type for SGLT-2 inhibitors?
Transport protein
What is the location for the actions of Metformin?
Hepatocyte mitochondria
What is the location for the actions of DPP-4 inhibitors?
Vascular endothelium
What is the location for the actions of Sulphonylureas?
Pancreatic beta cells
What is the location for the actions of SGLT-2 inhibitors?
Proximal convoluted tubule
What is the action of Metformin?
Decreased gluconeogenesis
What is the action of DPP-4 inhibitors?
Increased plasma incretin levels
What is the action of Sulphonylureas?
Insulin secretion
What is the action of SGLT-2 inhibitors?
Decreased glucose reabsorption
What are the 3 key steps to pharmacology?
- Identify the patient’s problem
- Specify the therapeutic objective
- Select a drug on the basis of comparative efficacy, safety, cost and sustainability
What does it mean if a drug is ionized?
Ionized = less lipid soluble
Less absorption, into blood
Good distribution, once in blood
What are the main side effects of Metformin?
GI effects
When is Metformin most effective?
In the presence of endogenous insulin, so with some residual functioning pancreatic islet cells.
What are the main side effects of DPP-4 inhibitors?
Upper respiratory tract infections
When are DPP-4 inhibitors only effective?
When some residual pancreatic beta-cell activity is present
What are the main side effects of Sulphonylurea?
- Weight gain
2. Hypoglycaemia
When is Sulphonylurea only effective?
When some residual pancreatic beta-cell activity is present
How can weight gain associated with sulphonylurea be mitigated?
The concurrent administration with Metformin
What is an example of a Sulphonylurea?
Gliclazide
What is an example of a DPP-4 inhibitor?
Sitagliptin
What is an example of a SGLT-2 inhibitor?
Dapaglifozin
What is gliclazide an example of?
Sulphonylurea
What is sitagliptin an example of?
DPP-4 inhibitor
What is dapaglifozin an example of?
SGLT-2 inhibitor
What are the main side effects of SGLT2 inhibitors?
- Uro-genital infections
- Slight decrease in bone density
- Can worsen beta-ketoacidosis (stop immediately)1
What can SGLT2 inhibitors cause?
- Weight loss
2. Reduction in BP
When is SGLT2 less effective?
Patients with renal impairment
