Antihyperlipidemi Drugs: Ezetimibe and Omega Fatty Acids

Question 1

The last category of lipid lower drugs is a cholesterol absorption inhibitor called Ezetimibe. What is the use?

Answer 1

Inhibits intestinal absorption of cholesterol and phytosterols
–lowers LDL

Question 2

What is the MOA for Ezetimibe?

Answer 2

Selective Inhibitor of NPC1L1 in jejunal enterocytes which takes up cholesterol from the lumen

• -reduces cholesterol absorption but however increases cholesterol synthesis (need to use a statin)
• -reduced delivery of the cholesterol to the liver leads to upregulation of LDL receptors which enhances LDL clearance.

Question 3

The actions of ezetimibe are complementary to those of statins. Therefore combined therapy does what?

Answer 3

Prevents enhanced cholesterol synthesis and the increase in cholesterol absorption.
–reduces LDL levels

Question 4

Ezetimibe is effective even in the absence of dietary cholesterol, how?

Answer 4

Inhibits reabsorption of cholesterol excreted in bile

Question 5

What are the uses of Ezetimibe?

Answer 5

Used in combo with a statin in patients unable to reach their LDL goal on statin monotherapy

Question 6

What are the adverse effects and drug interactions of Ezetimibe?

Answer 6

Adverse:
Low incidence of reversible impaired hepatic function
Drug Interactions:
Bile acid sequestrants inhibit absorption of ezetimibe. Therefore do not administer together

Question 7

Next drugs are the Omega 3 fatty acids, Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA). What is their role in lipid lowering?

Answer 7

Reduce plasma TG

• -reduce TG biosynthesis and increase fatty acid oxidation in the liver
• -long term may increase HDL

Question 8

What is the FDA approved omega 3 product ?

Answer 8

Lovaza

–indicated as an adjunct to diet to reduce triglyceride levels in adult patients with very high TG levels

Question 9

In summary what is the best drug for LDL lowering?

Answer 9

Statins

Question 10

Combination drug therapy is used in what situations?

Answer 10

1. Patients unable to reach their LDL goal in a single drug
2. Patients with combined hyperTAG and hypercholesterolemia that cannot be adequately controlled with a single drug
3. Patients with elevated LDL and low HDL levels

Question 11

What are the suggested drug therapy for dyslipidemias?

Answer 11

Elevated LDL: Initial Drug = Statin and Additions = Niacin, Resin and Ezetimibe
Elevated LDL and TG: Initial Drug= Statin and Additions = Niacin and Fibrate
Isolated low HDL: Initial Drug= Statin and Additions= Niacin
Isolated Severe HyperTAGs: Initial Drug = Fibrate and Additions = Statin

Question 12

Statins and Pregnancy?

Answer 12

Contraindicated

Question 13

Gemfibrozil and Fenofibrate and pregnancy?

Answer 13

Should be used in pregnancy only if the potential benefits justifies the potential risk to the fetus

Question 14

Niacin and Pregnancy?

Answer 14

Safety is unknown

Question 15

Cholestyramine and Colestipol and Pregnancy?

Answer 15

Interferes with absorption of important nutrients

Question 16

Colesevlam and Pregnancy?

Answer 16

Can be used during pregnancy

Question 17

Ezetimibe?

Answer 17

Skeletal defects in some animal studies