Oral hypoglycemics 1 - slides 1-17

Question 1

What is the treatment order for T2DM after diagnosis?

Answer 1

Life style changes (weight loss)
If glucose isn’t well controlled after lifestyle changes, add monotherapy (one oral med - usually metformin)
If still not controlled, add another oral drug
Then last would be adding another oral drug or adding insulin to the 2 drug regimen

Question 2

T2DM is marked by _____________ and _____________

Answer 2

Blunted insulin response
Inadequate glucagon suppression after meals

Too much glucagon, not enough insulin

Question 3

What drugs stimulate the pancreas to make more insulin?

Answer 3

Sulfonylureas
Meglitinides
(Oral hypoglycemics)

Question 4

What drugs re-sensitize the body to insulin and/or control hepatic glucose production?

Answer 4

Thiazolidinediones
Biguanides
(Oral antihyperglycemics)

Question 5

What drugs slow the absorption of starches?

Answer 5

Alpha glucosidase inhibitors

Question 6

What drugs suppress glucagon, decrease gastric emptying, and decrease food intake (increase satiety)?

Answer 6

Incretins (glucagon like peptides)

DPP4 inhibitors

Question 7

What drugs inhibit sodium reabsorption in the proximal tubule?

Answer 7

Sodium-glucose transport 2 inhibitors

Question 8

What are the first generation sulfonylureas? second generation? Whats the difference?

Answer 8

1st gen: Chlorpropamide, tolazamide, tolbutamide
2nd gen: Glimepride, Glipizide, Glyburide

2nd generation are 100x more potent, have less side effects

Question 9

How do sulfonylureas work?

Answer 9

They are ATP dependent K+ channel modulators

They block the channels on beta-cells in the pancreas, which causes depolarizaiton/opening of Ca++ channels to cause insulin release

Question 10

Effect of sulfonylureas?

Answer 10

They decrease basal hepatic glucose production, decrease gluconeogenesis and glycogenolysis
Increase insulin receptor sensitivity and receptor number
Decrease glucagon levels (secondary to increased insulin and somatostatin release)

Question 11

How are sulfonylureas metabolized?

Answer 11

Almost all extensively metabolized in the liver, there are some active metabolites
Excreted in the urine
Highly protein bound

Question 12

Cautions with sulfonylureas?

Answer 12

Use cautiously in renal or hepatic insufficiency

Caution in pregnancy bc it can cross the placenta, may deplete insulin from fetal pancreas

Question 13

Which drug has a disulfuram like reaction with alcohol?

Answer 13

Chlorpropamide

Question 14

Which drugs are the most likely to produce hypoglycemia?

Answer 14

Chlorpopamide and glyburide

Question 15

Describe chlorpopamide

Answer 15

Long acting, has the highest rate of side effects

Avoid in elderly

Question 16

How does glimepiride work, besides the normal sulfonylurea mechanism?

Answer 16

May enhance sensitivity of peripheral tissues to insulin
More rapid glucose control
May enhance hypoglycemia

Question 17

How is glimepiride administered?

Answer 17

Once per day

Question 18

Can glimepiride be used with insulin?

Answer 18

Yes - it can decrease the dose of insulin required

Question 19

How is glipizide administered?

Answer 19

Orally, 30 mins before meal
Short duration, so you have less hypoglycemia risk
There is also an extended once daily formulation

Question 20

How is glyburide administered?

Answer 20

Once daily dosing

Question 21

Cautions with glyburide?

Answer 21

Most frequent hypoglycemia (20-30%)
May suppress glucose inhibition of insulin release
Glyburide is also associated with increased CV risk

Question 22

Which sulfonylurea is associated with increased CV risk?

Answer 22

Glyburide

Question 23

Adverse effects of sulfonylureas?

Answer 23

Hypoglycemia (enhanced by alcohol)
Weight gain
Constipation, nausea, diarrhea
Rash, pruritus, increased sensitivity to sunlight
Leucopenia, thrombocytopenia, aplastic anemia (rare)
Resistance may develop with time
Glyburide may increase CV risk

Question 24

Contraindications for sulfonylureas?

Answer 24

Diabetic ketoacidosis with or without coma
Type 1 diabetes (can’t release insulin that isn’t there)
Pregnancy, breast feeding

Question 25

Drug interactions for sulfonylureas?

Answer 25

Protein binding
Hyperglycemic drugs decrease effectiveness
Disulfuram like reactions (Chlorpropamide)

Question 26

How do Meglitinides work?

Answer 26

They are also K+ atp channel modulators
They block the K+ channels in the beta cells to increase insulin secretion
Insulin is released relative to glucose levels!

Question 27

How are sulfonylureas and meglitinides different?

Answer 27

Sulfonylureas release insulin independent of glucose levels

Meglitinides release insulin relative to glucose levels

Question 28

Pharmacokinetics of meglitinides?

Answer 28

Highly protein bound, hepatic metabolism

R is CYP3A4, N is 2C9

Question 29

How are meglitinides dosed?

Answer 29

Take before meals
Repaglinide = 30 mins
Nateglinide = 1 to 10 mins

Question 30

Pharmacodynamics of meglitinides?

Answer 30

Peak effectiveness 1 hour, duration 3 to 4 hours

Question 31

True or False: Meglitinides work well combind with other drugs

Answer 31

True and false…

OK to be combined with metformin, not other drugs!

Question 32

True or false: Never miss a dose of Meglitinides

Answer 32

False - if you miss a meal, skip the dose

Question 33

Adverse effects of Meglitinides?

Answer 33

Upper respiratory infections
Hypoglycemia (moreso with Repaglinide)
Weight gain
Headache
Nausea
Joint pain
Use with caution in liver problems