Treatment Of DM2

Question 1

Insulin Secretagogues:

• Sulphonylureas - Glibenamide, Glicazide, Glimeperide, Glipizide, Tolbutamide
• M.O.A
• A.E’s

Answer 1

M.O.A - bind to sulphonylurea rec (SUR1) on surface on pancreatic B cells - close K-ATP channels, which causes depolarization, which opens Ca channels, influx of Ca, which stimulates exocytosis of insulin

A.E’s - hypoglycaemia, weight gain, GI disturbance

Question 2

Insulin Secretagogues: Meglitinides - Repaglinide and Nateglinide

• M.O.A
• A.E’s

Answer 2

M.O.A - Nateglinide binds SUR1, Repaglinide binds to a site nearby - both stimulate insulin release the same as sulphonylureas

Question 3

Insulin Sensitisers: Biguanides - Metformin

• M.O.A
• A.E’s

Answer 3

M.O.A - unknown, but does involve activation of Adenosine Monophosphate Protein Kinase (AMPK) in hepatocytes - key regulator in fat and protein metabolism

• increases glucose uptake, increases glycolysis, decreases gluconeogenesis
• also improves lipid profile by decreasing lipogenesis and increasing HDL production

A.E’s - GI upset, lactic acidosis so c/i in renal insufficiency

Question 4

Insulin Sensitisers: Thiazolidinediones/ Glitazones - Pioglitazone, Rosiglitazone

• M.O.A
• A.E’s

Answer 4

M.O.A - bind to peroxisome proliferator- activated receptor y (PPAR-y) in cell nucleus - causes activation of transcription of several genes whose products are important in insulin signaling - increases insulin sensitivity

A.E’s - weight gain, oedema, hepatotoxicity, HF

Question 5

Drugs affecting incretins: DPP-4 inhibitors - all end in “-gliptin”

• What are incretins?
• M.O.A
• A.E’s

Answer 5

Incretins - released from intestinal mucosal cells into the bloodstream in response to food ingestion - cause a glucose-induced insulin response

M.O.A - inhibit Dipeptidylpeptides 4 (DPP-4), which inhibits GLP-1, which causes increased insulin release and decreased glucagon release

A.E’s - assoc with development of acute pancreatitis, nausea, nasopharyngitis

Question 6

Drugs affecting incretins: GLP-1 receptor agonists - Exenatide, Liraglutide, Lixisenatide

• M.O.A
• A.E’s

Answer 6

M.O.A - mimic endogenous GLP-1 activity

A.E’s - nausea, GI disturbance, hypoglycaemia

Question 7

SGLT-2 Inhibitors - all end in “-gliflozin”

• M.O.A
• A.E’s

Answer 7

M.O.A - inhibit SGLT-2, which decreases glucose reabsorption and increases urinary excretion of glucose

Question 8

Glucosidase Inhibitors; Acarbose

• M.O.A
• A.E’s

Answer 8

M.O.A - inhibit intestinal brush border enzyme a-glucosidase, which decreases absorption of glucose

A.E’s - GI disturbance