Lipid Lowering Drugs

Question 0

HMG CoA Reductase Inhibitor

Answer 0

Atorvastatin (Lipitor)

Question 1

Required Lipid Lowering drugs

Answer 1

1) Atorvastatin Calcium
2) Fenofibrate
3) Colesevelam
4) Niacin
5) Ezetimibe

Question 2

Atorvastatin has a long/short half life and is metabolized how?

Answer 2

Long, 3A4 and 2C9

Question 3

MOA of Atorvastatin

Answer 3

• Completely inhibit HMG CoA reductase- blocking rate limiting step in cholesterol synthesis.
  a) Increase synthesis of hepatic LDL receptors and increase removal of LDL particles from circulation.
  b) Enhance clearance of LDL precursors (VLDL and IDL)
  c) May also decrease VLDL

Question 4

Statin effects on plasma lipids and lipoproteins (Atorvastatin)

Answer 4

• Lower LDL (20-55%)
• Trig concentration decreased (20%)
• HDL increase (5-10%)

Question 5

First line treatment for hypercholesterolemia?

Answer 5

Statin- Atorvastatin

Question 6

What other potential effects can statin have?

Answer 6

Cardioprotective effects. ie: Lowering CRP levels, anti-inflammatory, etc.

Question 7

Pharmacokinetics of Statins

Answer 7

Given orally, usually in evening.

• 1st pass metabolism by liver. Half life varies from 3-20 hours.
• Statins are excreted by the liver into the bile

Question 8

Adverse effects of Statins

Answer 8

1) GI irritation, headache, rash
2) Hepatotoxicity
3) Myopathy
* Usually in 1st 6 mos.

Question 9

Precautions and contraindications with Statins

Answer 9

1) Pregnancy and lactation

2) Liver disease

Question 10

Name a fibric acid

Answer 10

Fenofibrate (Tricor, Trilpix)

Question 11

MOA of fibric acids (Fenofibrate)

Answer 11

-Agonists at peroxisome proliferator activated receptor-a (PPAR-a)- Increases fatty acid oxidation.

Question 12

Bile Acid Binding resins

Answer 12

Colesevelam (Welchol)

Question 13

Fibric acids effects on plasma lipids and lipoproteins

Answer 13

• Lower VLDL concentration, thus lowering trig concentrations.
• Plasma HDL increases
• Variable effects on LDL levels
• Increase LP lipase

Question 14

MOA of Bile Acid Binding resins (Colesvelam)

Answer 14

_Bind bile acid in the intestine and prevent their reabsorption.

• This decreases the feedback inhibition of the enzyme converting cholesterol to bile acids and results in increased breakdown of hepatic cholesterol.
• Increased catabolism of cholesterol leads to an increased number of LDL receptors, similar to statins. However, this is somewhat offset by an increase in HMG CoA reductase activity.

Question 15

Effects on Plasma lipids and lipoproteins for Bile Acid Binding resins(Colesevelam)

Answer 15

• Lower LDL levels (10-20%)
• Small increase in HDL (5%)
• No net effects on VLDL levels

Question 16

Niacin (Nicotinic Acid) MOA:

Answer 16

A) In adipose tissue, niacin inhibits the lipolysis of TGs by hormone-sensitive lipase, which reduces transport of free fatty acids to the liver and decreases hepatic TG synthesis.
B) In the liver, reduces TG synthesis by inhibiting both the synthesis and esterification of FA’s-lower VLDL
C) Raises HDL levels by decreasing the fractional clearance of HDL-apoA-I rather than by enhancing HDL synthesis.

Question 17

Niacin effect on plasma lipids and lipoproteins

Answer 17

• Rapidly lowers TG levels by lowering VLDL (35-50%)
• More slowly lowers LDL (25%)
• Increases HDL (15-30%)

Question 18

Ezetimibe (Zetia) MOA:

Answer 18

1) Inhibits the intestinal absorption of cholesterol and

2) Inhibits reabsorption of cholesterol excreted in the bile. Inhibits cholesterol transport protein, NPC1L1

Question 20

Ezetimibe Effect on Plasma lipids and lipoproteins

Answer 20

-Primary effect is to reduce LDL levels (18-25%)

Question 21

Therapeutic use of Fibric Acids (Fenofibrate)

Answer 21

Patients with elevated Trigs

Question 22

Adverse effects of Fibric Acids (Fenofibrate)

Answer 22

GI, Myositis (with statins)

Question 23

Bile Acid Binding Resins (Colesevelam) uses

Answer 23

-Best used with statins

Question 24

Bile Acid Binding Resins (Colesevelam) Adverse effects

Answer 24

GI (bloating, dyspepsia, and constipation).

-Mild steatorrhea

Question 25

Niacin therapeutic uses

Answer 25

Patients with hypertriglyceridemia and elevated LDLs.

-Especially useful in pts with hyper trigs and low HDL

Question 26

Niacin adverse effects

Answer 26

1) Intense cutaneous flush and pruritis with initial doses.
2) GI disturbances
3) More severe, less frequent include hepatic toxicity, activation of peptic ulcer, hyperglycemia, and decreased glucose tolerance, and hyperuricemia.

Question 27

Ezetimibe uses

Answer 27

Adjunct with statins to reduce LDL levels. Used alone if patients intolerant to statins.

Question 28

Adverse effects of Ezetimibe

Answer 28

Diarrhea, low incidence of reversible impaired hepatic function.