Pharmacology of Diabetes Flashcards
Metformin Dipeptidyl-peptidase 4 (DPP) inhibitors Sulphonylurea Sodium glucose co-transporter (SGLT2) inhibitors
What is metformin used for?
- Glycemic control in type 2 diabetes mellitus
- For insulin resistance in polycystic ovary syndrome (PCOS)
What is the primary drug target of metformin?
- 5’-AMP-activated protein kinase (AMPK)
What is the drug target type of metformin?
- Enzyme antagonist
What is the location of action of metformin?
- Hepatocyte mitochondria (Therapeutic effects)
- Gastrointestinal mitochondira (Adverse effects)
What are the mechanism of action of metformin?
- Metformin is uptaken into the hepatocytes by organic cation transporter-1 (OCT1)
- Metformin inhibits mitochondrial complex I → preventing the production of mitochondrial ATP → increase cytoplasmic ADP:ATP & AMP:ATP ratios
- These changes activate 5’-AMP-activated protein kinase (AMPK), an enzyme that plays an important role in the regulation of glucose metabolism
- Increases in AMP:ATP ratio inhibit fructose-1,6-bisphosphatase enzyme → inhibition of gluconeogenesis
- Increases in AMP:ATP ratio inhibit fructose-1,6-bisphosphatase enzyme → inhibition of adenylate cyclase & decreasing the production of cyclic adenosine monophosphate (cAMP)
- Activated AMPK phosphorylates two isoforms of acetyl-CoA carboxylase enzyme → inhibiting fat synthesis → fat oxidation → reducing hepatic lipid stores & increasing liver sensitivity to insulin
What are the main adverse effects of metformin (1)?
-
GI side effects (Abdominal pain / Decreased appetite / Diarrhoea / Vomiting)
- Presence of OCT-1 in the gastrointestinal tract
When is metformin most effective?
- Most effective in the presence of endogenous insulin, so it’s most effective with some residual functioning pancreatic islet cells
What is DPP-4 inhibitors used for?
- Management of type 2 diabetes mellitus
What is the primary drug target of DPP-4 inhibitors?
- Dipeptidyl peptidase-4
What is the drug target type of DPP-4 inhibitors?
- Enzyme antagonist
What is the mechanism of action of DPP-4 inhibitors?
- DPP-4 inhibitor inhibit DDP-4
- Decrease in metabolism of incretins (GLP-1) in the plasma
- Increase in GLP-1
- Increase in insulin when needed
- Decrease glucagon when not needed & slow down digestion and appetite
What is the location of action of DPP-4 inhibitors?
- Vascular endothelium
What are the main adverse effects of DPP-4 inhibitors (2)?
- Upper respiratory tract infections (headache / runny nose / sore throat)
- Serious allergic reaction (less common)
When is DPP-4 inhibitors most effective?
- Most effective in the presence of endogenous insulin, so it’s most effective with some residual functioning pancreatic islet cells
What is the benefit of DPP-4 inhibitors over the other antidiabetic drugs?
- It does not appear to cause weight gain
What is sulfonylurea used for?
- Management of type 2 diabetes mellitus
What is the primary drug target of sulfonylurea?
- ATP-sensitive potassium channel (KATP)
What is the mechanism of action of sulfonylurea?
- Inhibit KATP
- Leads to depolarisation of membrane
- Ca2+ influx
- Increase in insulin vesicle exocytosis
What is the drug target type of sulfonylurea?
- Ion channel antagonist
What is the location of action of sulfonylurea?
- Pancreatic beta cell
What are the main adverse effects of sulfonylurea (2)?
- Weight gain
- Hypoglycaemia
What are sodium glucose co-transporter (SGLT2) inhibitors used for?
- Management of type 1 diabetes mellitus
What is the mechanism of action of SGLT2 inhibitors?
- Inhibits SGLT2
- Decrease glucose reabsorption
- Increase urine glucose secretion
What is the primary drug target of SGLT2 inhibitors?
- Sodium glucose co-trasporter (SGLT2)
