pharmacology of diabetes Flashcards
what is the purpose of metformin?
decrease glucose production y liver and increase insulin sensitivity of body tissues. Also has an anorexiant effect
what is meant by an ‘anorexiant effect’?
appetite suppression, thereby reducing caloric intake
what are the common side effects associated with metformin?
diarrhoea, nausea, abdominal pain, low blood glucose, high lactic acid levels
as Metformin is very polar, how does it move across body compartments?
through organic cation 1 (OCT-1) transporters
where is expression of OCT-1 transporters the highest?
liver hepatocytes, small intestinal enterocytes and renal proximal tubules
What is the primary drug target of metformin?
AMP activated protein kinase (enzyme)
what is the primary mechanism of action of Metformin?
activates AMPK in hepatocyte mitochondria. This inhibits ATP production. This blocks gluconeogenesis and subsequent glucose output. It also blocks adenylate cyclase which promotes fat oxidation
Where is the primary site of metformin action?
hepatocyte mitochondria
When is Metformin most effective?
in the presence of endogenous insulin so is most effective with so residual functioning islet cells
What is the drug target of Dipeptidyl-peptidase 4 (DPP-4) inhibitors such as sitagliptin?
DPP-4
Where is the primary site of action of DPP-4 inhibitors?
vascular endothelium
What is the primary mechanism of action of DPP-4 inhibitors?
inhibit DPP-4 reducing the metabolism of incretins. Incretins stimulate the production of insulin when it is needed.
What are the main side effects of DPP-4 inhibitors such as Sitagliptin?
upper respiratory tract infections. flu like symptoms.
What must be present for DPP-4 inhibitors to work?
only effective when some residual pancreatic beta-cell activity is present as act by augmenting insulin secretion
What is the primary effect of Sulphonylurea?
Inhibition of ATP sensitive potassium channels on pancreatic beta cells causing depolarization which stimulates calcium influx and subsequent insulin vesicle exocytosis
What is the drug target of Sulphonylurea?
ATP-sensitive potassium channel on the pancreatic beta cells
What are the main side effects caused by Sulphonylurea?
Weight gain and hypoglycaemia
What has to be present for Sulphonylurea to be effective?
As act by augmenting insulin secretion, must be some residual beta-cell activity present
How can the weight gain caused by Sulphonylurea be mitigated?
concurrent administration with metformin
What is the primary drug site for SGLT2 (sodium-glucose co-transporter) inhibitors?
SGLT2 transport protein in the proximal convoluted tubule
What is the primary mechanism of action for SGLT2 inhibitors?
Reversibly inhibits sodium-glucose co-transporters 2 in the renal proximal convoluted tubule to reduce glucose reabsorption and increase urinary glucose excretion
what are the main side effects associated with SGLT2 inhibitors?
Uro-genital infections due to increased glucose load. decrease in bone formation. can worsen diabetic ketoacidosis
In what patients will SGLT2 inhibitors be less effective?
patients with impaired renal function
