Diabetes Core Drugs Flashcards
(27 cards)
What is the primary mechanism of metformin?
- Primary effect – metformin activates AMPK in hepatocyte mitochondria
- This inhibits ATP production
- This blocks gluconeogenesis and subsequent glucose output
- Also blocks adenylate cyclase which promotes fat oxidation
- Both help to restore insulin sensitivity
What is the target of metformin and primary site of action?
- 5′-AMP-activated protein kinase (AMPK)
2. Primary site of metformin action is the hepatocyte mitochondria
What are the main side effects of metformin?
GI side effects (20-30% of patients)
e.g. Abdominal pain, decreased appetite, diarrhoea, vomiting)
How can you reduce the side effects of metformin?
- Particularly evident when very high doses are given
- A slow increase in dose may improve tolerability
What does metformin need to access tissues and why?
- Metformin is highly polar
- Requires organic cation transporter-1 (OCT-1) to access tissues
- Explains why it can accumulate in the liver (therapeutic effect) and gastrointestinal tract (side effects)
When is metformin most effective?
in the presence of endogenous insulin so is most effective with some residual functioning pancreatic islet cells
In 2020 in West London how commonly were these drugs prescribed?
- Metformin: 4th
- Sitagliptin: 49th
- Gliclazide: 15th
- Dapaglifozin: 127th
What is an example of a Dipeptidyl-peptidase 4 (DPP-4) inhibitor?
Sitagliptin
What is the primary mechanism of action for DPP-4 inhibitors?
- Primary effect - Work by inhibiting the action of DPP-4
- This enzyme is present in vascular endothelium and can metabolise incretins in the plasma.
- Incretins (e.g. GLP-1) are secreted by enteroendocrine cells and help stimulate the production of insulin when it is needed (e.g. after eating) and reduce the production of glucagon by the liver when it is not needed (e.g. during digestion)
- Incretins also slow down digestion and decrease appetite.
What is the drug target of DPP4 inhibitor and primary site of action?
- DPP-4
- primary site of DPP-4 inhibitor action is the vascular endothelium
What are the main side effects of DPP4 inhibitors?
Upper respiratory tract infections (5% of patients) Flu-like symptoms e.g. headache, runny nose, sore throat
What are the. less common but serious side effects of DPP4 inhibitors?
Serious allergic reactions/ avoid in patients with pancreatitis
What is better about DPP4 inhibitors than other anti-diabetic drugs but metformin do?
not appear to cause weight gain.
When are DPP4 inhibitors most effective?
DPP-4 I’s act mainly by augmenting insulin secretion and consequently are effective only when some residual pancreatic beta-cell activity is present
What is an example of a sulphonylurea?
Gliclazide
How do sulphonylureas work?
- Primary effect – 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 the target for sulphonylureas and where is primary site of action?
- ATP-sensitive potassium channel
- The primary site of SUs inhibitor action is the pancreatic beta cell
What are the main side effects of sulphonylureas?
- Weight gain is a likely side effect
2. Hypoglycaemia (2nd most common)
When are sulphonylureas most effective?
The sulfonylureas act mainly by augmenting insulin secretion and consequently are effective only when some residual pancreatic beta-cell activity is present
How is weight gain mitigated with sulphonylureas?
by the concurrent administration with metformin
Why is the risk. of hypoglycaemia important with sulphonylureas?
The risk of hypoglycaemia associated with sulfonylureas should be discussed with the patient, especially when concomitant glucose-lowering drugs are prescribed
What is an example of Sodium-glucose co-transporter (SGLT2) inhibitors?
Dapaglifozin
What is the primary mechanism action of SGLT-2 inhibitors?
- Reversibly inhibits sodium-glucose co-transporter 2 (SGLT2) in the renal proximal convoluted tubule
- to reduce glucose reabsorption and increase urinary glucose excretion
What is the drug target and primary site of action of SGLT-2 inhibitors?
-SGLT2
-The primary site of SGLT2 inhibitor action is the proximal convoluted tubule
