1 - Lipid Disorders

Question 1

What causes atherosclerosis?

Answer 1

Elevated plasma cholesterol, primarily derived from LDL’s

Question 2

What are risk factors for increased LDL?

Answer 2

• Smoking
• Hypertension
• Diabetes mellitus
• Genetics

Question 3

Why should you control plasma cholesterol?

Answer 3

Can lead to atherosclerosis

Question 4

Why should you control plasma triglycerides?

Answer 4

Can lead to pancreatitis

Question 5

What causes pancreatitis?

Answer 5

Elevated triglycerides, primarily chylomicrons and VLDL’s

Question 6

What does the body do when it needs cholesterol?

Answer 6

Liver synthesized VLDL, which are similar to chylomicrons

Question 7

What is the function of lipoprotein lipase?

Answer 7

Hydrolyzes chylomicrons, producing free fatty acids

Question 8

What are some possible sites to decrease cholesterol?

Answer 8

• Decrease dietary intake
• Decrease absorption of cholesterol or reabsorption of bile acids
• Decrease endogenous cholesterol synthesis
• Decrease LDL levels by decreasing VLDL or increasing LDL receptors

Question 9

What are some non-pharm approaches to decrease cholesterol?

Answer 9

• Increase dietary fiber (100g each day)

- Increase omega-3 fatty acids

Question 10

What are statins?

Answer 10

HMG-CoA reductase inhibitors

Question 11

What are some examples of statins?

Answer 11

• Rosuvastatin
• Atorvastatin
• Simvastatin

Question 12

When are statins the 1st line therapy?

Answer 12

For most px w/ risk of coronary heart disease

Question 13

What do statins do?

Answer 13

• Decrease LDL levels
• Decrease triglyceride levels
• Decrease cardiac morbidity, mortality, and reduce incidence of stroke

Question 14

What is important about HMG-CoA reductase?

Answer 14

Rate limiting step of cholesterol synthesis

Question 15

Statins are best given in the _____

Answer 15

Evening

Question 16

Are statins safe in pregnancy?

Answer 16

No

Question 17

What are some adverse effects of statins?

Answer 17

Myalgia, muscle weakness

Question 18

What is contraindicated w/ statins and why?

Answer 18

• Statins undergo first pass metabolism by CYP 3A4

- Contraindicated w/ CYP 3A4 inhibitors (grapefruit juice) because will increase bioavailability of statin

Question 19

What a flat dose response for statins mean?

Answer 19

Increasing the dose doesn’t increase effect (majority of statin LDL efficacy is w/ the starting dose)

Question 20

What drug is a cholesterol absorption inhibitors?

Answer 20

Ezetimibe

Question 21

What does ezetimibe do?

Answer 21

• Inhibits dietary and biliary cholesterol absorption

- Inhibits cholesterol transport protein NPC1L1

Question 22

What is a side effect of ezetimibe?

Answer 22

Reflex increase in cholesterol synthesis

Question 23

Which drugs are bile acid binding resins?

Answer 23

• Cholestyramine

- Colestipol

Question 24

When are bile acid binding resins used?

Answer 24

• Mild to moderate elevated LDL

- Effective w/ statins or nicotinic acid in high LDL levels

Question 25

How do bile acid binding resins work?

Answer 25

Binds bile acids in intestinal lumen, preventing reabsorption

Question 26

What are some adverse effects of bile acid binding resins?

Answer 26

- May increase VLDL levels - Decrease absorption of fat soluble vitamins - Nausea, constipation, bloating - Absorption of drugs altered

Question 27

Why would statins and ezetimibe be combined?

Answer 27

- Ezetimibie decreases cholesterol uptake in gut, which causes a reflex increase in cholesterol synthesis in liver - Statins block this increased synthesis

Question 28

Why would statins and bile acid binding resins be combined? Are they commonly combined?

Answer 28

- Statin inhibits synthesis of cholesterol and bile acid binding resins prevent reabsorption of bile, causing increased excretion - Together they decrease LDL levels - Not generally used b/c bile acid binding resins are poorly tolerated

Question 29

What can cause a px to fail to achieve the LDL-C target?

Answer 29

- Poor adherence - High baseline LDL-C - High-cholesterol diet - High cholesterol absorption - Variable statin response - Inability to tolerate statins

Question 30

What is the newest therapy for px that can't meet target levels of LDL? What is the name of the drug?

Answer 30

- Target LDL receptor PCSK9 by injecting human monoclonal Ab to PCKS9 to increase LDL receptors on liver - Drug = evolocumab

Question 31

What are the problems w/ cholesterol lowering drugs?

Answer 31

- Variation in px sensitivity to HMG-CoA reductase inhibitors - Evidence that ezetimibe plus simvastatin may be no more beneficial in plaque regression than simvastatin alone

Question 32

What are the potential ways to decrease plasma triglycerides?

Answer 32

- Decrease dietary triglycerides - Increase lipoprotein lipase activity - Decrease VLDL secretion from liver

Question 33

What is a non-pharm to decrease dietary triglycerides? What is the problem w/ this?

Answer 33

- Dietary fiber (soluble better than insoluble) | - Problem = need large amounts of fiber and long term effect and safety unknown

Question 34

Which drugs are fibrates?

Answer 34

- Fenofibrate - Gemfibrozil - Clofibrate

Question 35

What do fibrates do?

Answer 35

- Don't change LDL levels, but decrease incidence of non-fatal MI and stroke - Primarily decrease triglycerides and may increase HDL - Increase VLDL clearance and decrease VLDL secretion

Question 36

What is important to note about clofibrate?

Answer 36

- Increased mortality due to malignant and GI disease | - Only used in extreme unresponsive cases

Question 37

What are some adverse effects of fibrates?

Answer 37

- Flu-like (muscle cramps, tenderness, weakness) | - Avoid in hepatic or renal dysfunction

Question 38

What does nicotinic acid do?

Answer 38

- Increases HDL levels at low dose - Decreases VLDL production via inhibition of fatty acid release from adipose tissue => decreases triglycerides at higher dose

Question 39

What are some adverse effects of nicotinic acid?

Answer 39

- Poor tolerability - Skin flushing and pruritus - Exacerbation of peptic ulcer