Sulfonylureas, Meglitinides

Question 1

Sulfonylureas and Meglitinides are insulin secretagogues, what is their MOA?

Answer 1

Stimulate insulin production

Question 2

2nd generation sulfonylureas are more widely used and include which drugs?

Answer 2

Glipizide (Glucotrol)
Glyburide (Micronase, Diabeta)
Glimepiride (Amaryl)

(1st gen include: Tolbutamide (Orinase), Tolazimide(Tolinase), Chlorpropamide (Diabinese)

Question 3

Why are 2nd generation sulfonylureas more widely used and how are the two generations’ potency differ?

Answer 3

1st have more drug interaction and AE

2nd gen are 100x more potent, but no more effective

Question 4

MOA of Sulfonylureas: Main and minor

Answer 4

Main:
Stimulate release of insulin from pancreatic beta cells
Irrespective of glucose levels

Minor:
Enhance tissue sensitivity to insulin at peripheral sites, insulin made more effctive
Reduces hepatic glucose output

Question 5

Sulfonylureas are only useful in patients with some:

Answer 5

beta cell function (Type II diabetes)

Question 6

AE of Sulfonylureas:

Answer 6

**Hypoglycemia- exercise, missed meals, undernourished, longer acting sulfonylureas, alcohol
Nausea, fullness, heartburn
Pruritis, rash
Weight gain

Question 7

Use of sulfonylureas are CI when?

Answer 7

Patients with sulfonamide allergies

Question 8

When should sulfonylureas be taken and why?

Answer 8

30minutes before a meal

When taken w/o food absorption can be erratic

Question 9

How are sulfonylureas metabolized and why can this be harmful to some patients?

Answer 9

Metabolized by the liver to some active metabolites that may be renally excreted. Patients with renal failure may accumulate metabolites and lead to hypoglycemia

Question 10

Which sulfonylurea is better in patients with renal dysfunction and why?

Answer 10

Glipizde

Almost completely metabolized to inactive or weakly active products

Question 11

Why is the relatively short plasma half-life of a sulfonylurea misleading?

Answer 11

Although drug can be eliminated from the plasma it can still have a biologic effect

(Glyburide also has longer half life=dose once/day)

Question 12

How are glipizide and glipizide XL different?

Answer 12

Glipizide is usually BID (may be once in the elderly)

Glipizide XL is typically once a day and has less peaks/troughs

Question 13

Meglitinides, Repaglinide (Prandin) and Nateglinide (Starlix) MOA:

Answer 13

Stimulates insulin secretion from pancreatic beta cells

Exerts effects via different rc than sulfonylureas but efficacy is similar

Question 14

Which types of patients may meglitindes be a good choice for and why?

Answer 14

Patients with controlled fasting BG but uncontrolled postprandial hyperglycemia. Meglitinides reduce post-prandial hyperglycemia

Question 15

What is meglitinides onset and duration of action?

Answer 15

Quick onset and duration of action (concentrated around meal-time glucose)

Question 16

With meglitinides how is insulin release related to glucose levels?

Answer 16

Insulin release IS DEPENDENT upon existing glucose levels

if glucose lower, insulin release will be lower

Question 17

AE of Meglitinides: Repaglinide (Prandin) and Nateglinide (Starlix)

Answer 17

**Hypoglycemia
Heartburn, N/V/C/D
HA
Weight gain

Question 18

How is Meglitinides: Repaglinide (Prandin) and Nateglinide (Starlix) dosed?

Answer 18

Dosed 15-30mins before meals
Skip a meal, skip dose
Add meal, add dose

Question 19

Which Meglitinide is better for patients with renal impairment and why?

Answer 19

Repaglinidie, it is hepatically metabolized and 10% renally excreted
Nateglinide is hepatically metabolized to active metabolites that are renally excreted which may lead to accumulation and hypoglycemia in renal impairment