pharmacology of diabetes

Question 1

what is the purpose of metformin?

Answer 1

decrease glucose production y liver and increase insulin sensitivity of body tissues. Also has an anorexiant effect

Question 2

what is meant by an ‘anorexiant effect’?

Answer 2

appetite suppression, thereby reducing caloric intake

Question 3

what are the common side effects associated with metformin?

Answer 3

diarrhoea, nausea, abdominal pain, low blood glucose, high lactic acid levels

Question 4

as Metformin is very polar, how does it move across body compartments?

Answer 4

through organic cation 1 (OCT-1) transporters

Question 5

where is expression of OCT-1 transporters the highest?

Answer 5

liver hepatocytes, small intestinal enterocytes and renal proximal tubules

Question 6

What is the primary drug target of metformin?

Answer 6

AMP activated protein kinase (enzyme)

Question 7

what is the primary mechanism of action of Metformin?

Answer 7

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

Question 8

Where is the primary site of metformin action?

Answer 8

hepatocyte mitochondria

Question 9

When is Metformin most effective?

Answer 9

in the presence of endogenous insulin so is most effective with so residual functioning islet cells

Question 10

What is the drug target of Dipeptidyl-peptidase 4 (DPP-4) inhibitors such as sitagliptin?

Answer 10

DPP-4

Question 11

Where is the primary site of action of DPP-4 inhibitors?

Answer 11

vascular endothelium

Question 12

What is the primary mechanism of action of DPP-4 inhibitors?

Answer 12

inhibit DPP-4 reducing the metabolism of incretins. Incretins stimulate the production of insulin when it is needed.

Question 13

What are the main side effects of DPP-4 inhibitors such as Sitagliptin?

Answer 13

upper respiratory tract infections. flu like symptoms.

Question 14

What must be present for DPP-4 inhibitors to work?

Answer 14

only effective when some residual pancreatic beta-cell activity is present as act by augmenting insulin secretion

Question 15

What is the primary effect of Sulphonylurea?

Answer 15

Inhibition of ATP sensitive potassium channels on pancreatic beta cells causing depolarization which stimulates calcium influx and subsequent insulin vesicle exocytosis

Question 16

What is the drug target of Sulphonylurea?

Answer 16

ATP-sensitive potassium channel on the pancreatic beta cells

Question 17

What are the main side effects caused by Sulphonylurea?

Answer 17

Weight gain and hypoglycaemia

Question 18

What has to be present for Sulphonylurea to be effective?

Answer 18

As act by augmenting insulin secretion, must be some residual beta-cell activity present

Question 19

How can the weight gain caused by Sulphonylurea be mitigated?

Answer 19

concurrent administration with metformin

Question 20

What is the primary drug site for SGLT2 (sodium-glucose co-transporter) inhibitors?

Answer 20

SGLT2 transport protein in the proximal convoluted tubule

Question 21

What is the primary mechanism of action for SGLT2 inhibitors?

Answer 21

Reversibly inhibits sodium-glucose co-transporters 2 in the renal proximal convoluted tubule to reduce glucose reabsorption and increase urinary glucose excretion

Question 22

what are the main side effects associated with SGLT2 inhibitors?

Answer 22

Uro-genital infections due to increased glucose load. decrease in bone formation. can worsen diabetic ketoacidosis

Question 23

In what patients will SGLT2 inhibitors be less effective?

Answer 23

patients with impaired renal function