L30- Antidiabetic Drugs II (insulin secretagogues)

Question 1

Sulfonylureas:

• (1) ultimate goal
• (2) MOA

Answer 1

1- effective reduction of fasting plasma glucose and HbA1c

2- binds to SUR1 subunit –> blocks ATP sensitive K+ channel –> stimulate β-cells

Question 2

1st generation Sulfonylurea = (1)

• (longer/shorter) 1/2 life than 2nd gen.
• (3) main AE / contraindication

Answer 2

1- chlorpropamide

2- longer (but less potent)

3- hypoglycemia: mostly in elderly, a contraindication

Question 3

Chlorpropamide

• (1) alcohol association
• potentiates action of (2) hormone

Answer 3

(1st gen. sulfonylurea)
1- hyperemic flush w/ alcohol ingestion; due to inhibition of aldehyde dehydrogenase

2- ADH (vasopressin), especially in SiADH

Question 4

list the 2nd generation Sulfonylureas

Answer 4

• glyburide (glibenclamide)
• glipizide
• glimepiride

Question 5

2nd generation Sulfonylureas advantages

Answer 5

-more potent than 1st gen.

-lacks 1st gen. AEs
essentially replaced 1st gen.

Question 6

2nd generation Sulfonylurea AEs

Answer 6

Glyburide (glibenclamide)- hypoglycemia (20-30% users)

Glipizide: short half-life, lower chance of hypoglycemia (10-15% users)

Glimepiride: hypoglycemia (9-14% users, once a day use)

Question 7

all Sulfonylurea drugs may cause ______ AEs

Answer 7

• hypoglycemia

- weight gain

Question 8

list the insulin secretagogues (indicate more effective drug)

Answer 8

• sulfonylureas* (reduces FPG and HbA1c more)

- meglitinides

Question 9

Meglitinides:

• (1) list drugs
• (2) MOA

Answer 9

1- repaglinide, nateglinide

2- binds SUR1 –> inhibits ATP sensitive K+ channel –> stimulates insulin release

Question 10

Meglitinides:

• (1) list drugs
• (2) onset speed and duration in comparison with sulfonylureas
• (3) main advantage with sulfonyurea intolerance
• (4) regimen schedule

Answer 10

1- repaglinide, nateglinide

2- rapid onset, short duration

3- no sulfur for allergic patients

4- postprandial glucose regulators –> taken before each meal (omit if meal is missed)

Question 11

Meglitinides AEs

Answer 11

weight gain

Repaglinide- hypoglycemia
Nateglinide- lower hypoglycemic risk