Dyslipidemias

Front 1

Functions of lipoprotein lipase

Back 1

i. Mediates several key steps of the cholesterol cycle.
ii. Hydrolyzes triglycerides in chylomicrons to make free fatty acids available to peripheral tissues.

Front 2

How is a patient's triglyceride level affected with a genetic deficiency of LPL?

Back 2

Patients with a genetic deficiency of LPL have extreme hypertriglyceridemia.

Front 3

Describe the role of the LDL receptor in the cholesterol cycle.

Back 3

i. Primary mediator of LDL clearance from the plasma.
ii. Located in hepatic and peripheral tissues.
iii. Binds LDL and IDL from the plasma through ApoB-100, resulting in metabolism of these lipoproteins.
iv. The hepatic LDL-receptor is up-regulated by low levels of cholesterol in the liver resulting in more clearance of plasma LDL when hepatic cholesterol stores are low. Plasma LDL thus decreases.

Front 4

LDL goal for High Risk: CHD or CHD risk equivalent

Back 4

<100 mg/dL (optional goal: <70 mg/dL)

Front 5

LDL goal for moderately high risk: 2+ risk factors

Back 5

<130 mg/dL
(optional goal of 100 mg/dL)

Front 6

LDL goal for moderate risk: 2+ risk factors

Back 6

<130 mg/dL

Front 7

HDL goal:

Back 7

>40 mg/dL

Front 8

Triglyceride goal

Back 8

<150

Front 9

LDL goal for a lower risk (0 to 1 RF) pt

Back 9

<160

Front 10

What is the mechanism of action for stains?

Back 10

Statins inhibit HMG-CoA reductase. This enzyme catalyzes the rate limiting step of cholesterol synthesis.

Front 11

What are contraindications for statins?

Back 11

i. Active liver disease
ii. Pregnancy or lactation (Class X)
iii. Most statins have 1 or more drugs for which concurrent use is contraindicated. See below.

Front 12

What are important principles to notice regarding statins and drug interactions?

Back 12

1. Simvastatin has the most drug interactions.
2. Pravastatin has the least.
3. Concurrent use of gemfibrozil (Lopid®) and nearly every statin is either contraindicated or should result in a limited dose of the statin.

Front 13

What drugs are contraindicated with simvastatin?

Back 13

-Gemfibrozil (Lopid®) (CYP3A4 inhibitor)
-Amiodarone(Cordarone®), amlodipine (Norvasc®),--limit simvastain to 20 mg daily

Front 14

What drugs are interacts with rosuvastin?

Back 14

-Gemfibrozil (Lopid®)

Front 15

What are adverse side effects of statin?

Back 15

1. myopathy- -Simvastatin should not be dosed at 80 mg daily unless the patient has already received this dose for > 12 months. This was a FDA dose restriction change from June 2011.
2. Myalgia
3. liver enzyme elevation
4. rhabdomyolysis- life threatening and can cause acute renal failure

Front 16

What are risk factors for rhabdomyolysis with statin use?

Back 16

a. Renal insufficiency
b. Age > 65 years
c. Concurrent administration of gemfibrozil, niacin, or a drug that interacts with a statin resulting in statin accumulation.

**All statins have caused rhabdomyolysis, but it is rare

Front 17

How does rosuvastatin effect LDL levels?

Back 17

can lower 45%-55%

Front 18

How does atorvastatin effect LDL levels?

Back 18

37%- 51%

**

Front 19

What are other general ways statins effect lipid levels?

Back 19

1.All other statins effect LDL less than 50%
2. moderately increase HDL
3. moderately decrease triglycerides

Front 20

What are the clinical trial evidence of statins?

Back 20

i. Statins are the most studied drugs for dyslipidemia.
ii. Clinical studies have found the agents to reduce all-cause mortality, cardiovascular mortality, stroke, angina, and need for revascularization procedures.
1. Studies are predominantly for patients with various degrees of coronary artery disease. There is also a clear benefit in patients with diabetes.
2. Benefits directly associated with percent LDL reduction.
3. Drugs with endpoint data include: simvastatin, atorvastatin, pravastatin, and rosuvastatin.
4. It is likely there is a class effect is likely.

Front 21

What are the real world application points for statins?

Back 21

i. Statins have been proven to reduce mortality and other major clinical endpoints in several patient groups. They should be used first line for LDL reduction unless the triglycerides (TGY) > 500 mg/dL or if the patient has a contraindication to their use.
ii. The degree of benefit statins have on reducing clinical endpoints appears to be dependant on the degree of LDL lowering.
iii. They lower LDL more than any other class of lipid lowering therapy.
iv. Patients taking simvastatin, lovastatin, fluvastatin, or pravastatin should take their daily dose in the evening.
v. Patients taking atorvastatin, pitvastatin, or rosuvastatin may take their dose without regard to time of day.
vi. Be careful about drug interactions with other lipid drugs and drugs that inhibit the CYP 450 system.
vii. Monitor for efficacy 6 weeks following titration.
viii. Monitor for liver function tests (LFT’s) at baseline and then as clinically relevant.
ix. Myalgias are the most common adverse effect.
x. Rhabdomyolysis is rare, but life-threatening. Measure a CPK if they report muscle aches. Raise your index of suspicion for rhabdomyolysis if the patient has renal insufficiency, is older than 65 years, or if they are taking drugs that interact.

Front 22

What is the mechanism of action for niacin?

Back 22

i. Physiologically functions in the NAD-NADP oxidation-reduction system in tissue respiration.
ii. the MOA is not well understood, there are possible/likely outcomes

aka Nicotonic Acid, Vitamin B-3

Front 23

How does Niacin affect LDL, HDL, and triglyceride levels?

Back 23

↓ 5-25% (LDL) ↑ 15-35% (HDL) ↓ 20-50% (Tri)

Front 24

What are contraindications for Niacin?

Back 24

i. Liver disease
ii. Severe gout
iii. Active peptic ulcer
iv. Arterial bleeding

Front 25

What are precautions when choosing niacin for tx?

Back 25

i. Diabetes
ii. History of liver disease
iii. High alcohol consumption
iv. Renal disease
v. Predisposition to gout
vi. Pregnancy class C

Front 26

What are the drug interactions for niacin?

Back 26

1. Statins
2. Bile acid sequestrants
3. antihyperglycemic agents

Front 27

What are the adverse effects of Niacin?

Back 27

1. flushing
2. hyperglycemia
3. hepatic dysfunction
4. hyperuricemia
5. upper GI distress
6. Cardiac Arrhythmia in patients experiencing an acute coronary syndrome

Front 28

What are real world applications of Niacin?

Back 28

i. There are no strong studies showing niacin independently reduces mortality, cardiovascular mortality, or other clinically significant endpoints.
ii. Niacin is the best agent at increasing HDL.
iii. Most broad spectrum of lipid profile benefits.
iv. Flushing is a common reason for discontinuation. Pre-treatment with aspirin helps.
v. When switching from immediate to long-acting niacin, dose the long-acting niacin at 50% of the immediate release dose.
vi. Generally start Niaspan® at 500 mg daily and increase by no more than 500 mg increments at intervals of 4 weeks or more.
vii. Immediate release must be dosed three times daily for full efficacy.

Front 29

What is the mechanism of action for cholesterol absorption inhibitors?

Back 29

i. Ezetimibe inhibits the absorption of cholesterol at the brush border of the small intestine from bile and dietary intake. The result is reduced hepatic cholesterol stores and increases cholesterol clearance from the blood. Ezetimibe does not affect synthesis.

Front 30

What drugs are classified as cholesterol absorption inhibitor?

Back 30

1.Ezetimide
2. Ezetimibe/simvastatin

Front 31

How does ezetimibe affect lipid levels?

Back 31

↓ 20% (LDL) ↑ 0-5% (HDL) ↓ 5-11% (TGY)

Front 32

What are contraindications for ezetimibe?

Back 32

active liver disease (when combined with liver disease)

Front 33

What are the precautions for using ezetimibe?

Back 33

moderate to severe hepatic insufficiency

Front 34

What are the drug interactions for for ezetmibe?

Back 34

1. Cyclosporine
2. Fibrates

Front 35

What are the real world applications for ezeimibe?

Back 35

i. The drug is not as potent as other agents, but it has few side effects and drug interactions.
ii. Complementary mechanism of actions to statins. It is frequently used to lower LDL when the maximum appropriate dose of a statin has not resulted in achieving the LDL target.
iii. Ezetimibe dose: 10 mg daily, with or without meals

Front 36

MOA for fibric acid derivatives

Back 36

Activates peroxisome proliferator activated receptor alpha (PPAR-alpha)

Front 37

Lipid profile effects of fibric acid derivatives (aka fibrates)

Back 37

i. LDL: variable: ↓ 5-20% in many patients, but usually LDL increases in patients with very high triglycerides (i.e. >300 mg/dL).
ii. HDL: ↑10-35%
iii. Triglycerides: ↓ 20-50%

Front 38

Contraindications for fibric acid derivatives (aka fibrates)

Back 38

i. Pre-existing gallbladder disease
ii. Hepatic dysfunction
iii. Severe renal impairment

Front 39

Precautions for fibric acid derivatives (aka fibrates)

Back 39

i. Cholelithiasis
ii. Concomitant use of statins

Front 40

Drug interactions for fibric acid derivatives (AKA fibrates)

Back 40

i.Statins
ii.Ezetimibe (Zetia®)
iii.Glyburide (Micronase®, Diabeta®) and repaglinide (Prandin®)

Front 41

Adverse effects for fibric acid derivatives (AKA fibrates)

Back 41

i. Gallstones
ii. Myopathy
iii. Increased LFT’s

Front 42

Real world application for fibric acid derivatives

Back 42

i. Fibrates are first line therapy for treatment of high triglycerides. No agent lowers triglycerides more than fibrates. Niacin can lower them comparably.
ii. Caution must be used if these agents are combined with statins.
iii. Trilipix® (delayed release fenofibrate) was approved in December 2008 with an indication to be used with a statin.
iv. Administration: gemfibrozil twice daily with meals, fenofibrate once daily without regard to meals.
v. Watch for increases in LDL following initiation, especially in patients with very high triglycerides at baseline.

Front 43

MOA for bile acid sequestrants

Back 43

i. Bile acids, metabolites of cholesterol, are normally largely reabsorbed in the jejunum and ileum. They are then returned to the cholesterol cycle. Bile acid sequestrants are resins that complex with these bile acids preventing reabsorption. A negative feedback loop in the liver recognizes a decreased amount of bile acids resulting in increased hepatic uptake and catabolism of LDL, and thus lower levels of LDL.

Front 44

Lipid profile effects of bile acid sequestrants

Back 44

i. ↓ LDL 15-30%
ii. ↑ HDL 3-5%
iii. ↑ Triglycerides 0 to ~10%

Front 45

Contraindications for bile acid sequestrants

Back 45

i. Bowel obstruction
ii. Complete biliary obstruction
iii. Hypersensitivity

Front 46

Precautions for bile acid sequestrants

Back 46

i. Malabsorption disorders (particularly disorders of fat soluble vitamin absorption)
ii. Chronic constipation
iii. Triglycerides > 200 mg/dL

Front 47

Drug interactions for bile acid sequestrants

Back 47

i. BAS’s bind many/most drugs (too many to list) and impair absorption to varying degrees. Cholestyramine and colestipol are highly charged and have a strong binding affinity to anionic drugs. Colesevelam is not highly charged and appears to impair absorption of other drugs considerably less (or none at all).
ii. The effect is most clinically relevant for drugs that have a narrow therapeutic window, such as warfarin.
iii. The solution to this effect is to separate dosage of BAS’s from other drugs. This means other drugs should be taken 1 hr before or 4-6 hrs after a BAS. BAS drugs are administered 1-2 times/day.

Front 48

Adverse reactions for bile acid sequestrants

Back 48

i. Constipation/flatulence/bloating (infrequent with colesevelam)
ii. Steatorrhea
iii. Increased triglyceride concentration
iv. Malabsorption of fat soluble vitamins

Front 49

Real world info for bile acid sequestrants

Back 49

i. Side effects, drug interactions, and tablet burden result in the infrequent use of this class of agents.
ii. Colesevelam is preferred, due to less frequent drug interaction and reduced frequency of adverse effects.
iii. These drugs can be used in combination with statins.
iv. Have some glycemic reduction properties and are being used in some diabetics for this purpose.

Front 50

How often should monitoring be done?

Back 50

1. Every 6 weeks until goals are met for the lipid profile and dose titration
2. Every 4-6 mo once target goals are reached to monitor response and adherence to tx