Lipid Lowering Agents

Question 1

Most effective drugs for lowering LDL

Answer 1

HMG-CoA Reductase

Inhibitors (Statins)

Question 2

• Nonlipid beneficial cardiovascular actions of statins

Answer 2

– Promote plaque stability
– Reduce the risk for cardiovascular (CV)
events

Question 3

Statins can show

Answer 3

• Reduction of LDL cholesterol
• Elevation of HDL cholesterol
• Reduction of triglyceride levels

Question 4

Statin MOA

Answer 4

Mechanism of
action:
-Competitive
inhibitors of
hydroxymethylgluta
ryl (HMG) CoA
reductase, the ratelimiting step in
cholesterol
biosynthesis.

***Increase the # of
LDL receptors on
hepatocytes.

Question 5

Statins should be adminstered in the

Answer 5

evening – cholesterol synthesis

normally increases during the night

Question 6

Statins have a significant

Answer 6

first pass effect

Question 7

Lovastatin absorption is increased

Answer 7

food

Question 8

statin ADR

Answer 8

Common – headache, rash,
GI disturbances
• Rare AE: myopathy/rhabdomyolysis,
hepatotoxicity.

Question 9

Stain interactions

Answer 9

Drug interactions

– With other lipid-lower drugs, drugs that inhibit CYP3A4.

Question 10

Statin routine monitoring of

Answer 10

f serum creatine

kinase (CK) levels is not recommended.

Question 11

Check baseline aminotransferase levels

prior to initiating

Answer 11

statin therapy; do not

routinely monitor when on statins

Question 12

Recheck lipid panel

Answer 12

6 to 8 weeks after

initiation or change of treatment

Question 13

Hepatic Dysfunction

in statin therapy - Clinical studies -

Answer 13

0.5 to 3.0 percent occurrence of
persistent elevations in aminotransferases,
primary in the first 3 months, dose dependent.
• Rare – severe liver injury (typically 3 to 4 months
after initiation).

Question 14

statin previous ____

Answer 14

LFT prior to initiation (routine monitoring

of LFT now not necessary).

Question 15

ALT level more than 3x the upper level of
normal, confirmed on two occasions.
– Use different

Answer 15

statin, dose reduction, alternative day

therapy

Question 16

Statin can cause

Answer 16

muscle adverse events

Question 17

mild muscle injury

Answer 17

muscle aches, tenderness, or
weakness can localize to certain muscle
groups or be diffuse.

Question 18

myositis

Answer 18

– muscle inflammation, moderate

elevation of CK

Question 19

rhabdomyoloysis

Answer 19

– muscle disintegration

or dissolution.

Question 20

• If patient reports muscle symptoms,

Answer 20

btain

a CK blood level

Question 21

• CK value is > 10x increase

Answer 21

ULN: stop

therapy

Question 22

CK value is < 10x increase ULN

Answer 22

can
continue, follow symptoms and CK level
weekly, OR stop and re-evaluate

Question 23

• Routine monitoring of CK in asymptomatic

patients is

Answer 23

not necessary.

Question 24

Niacin uncommonly

Answer 24

Uncommonly used – lower LDL

Question 25

Niacin increases

Answer 25

• Increases HDL levels – Does little to improve outcomes – AIM-HIGH trial 2011

Question 26

Niacin combo with __ no longer used

Answer 26

Combo of niacin with statin – no longer used

Question 27

Niacin concerns about

Answer 27

Concerns about niacin monotherapy (AIMHigh trial)

Question 28

Niacin can rais

Answer 28

Can raise HDL – but generally no recommendation to use for this

Question 29

Niacin use is alos

Answer 29

limited as it is not well-tolerated

Question 30

niacin ADR

Answer 30

– Skin (flushing, itching) • Intense flushing initially; can pretreat with aspirin 325mg 30 minutes before each dose. ***Decreased with sustained-release (SR) version of niacin – Gastrointestinal (gastric upset, n/v, diarrhea) – Hepatotoxicity (severe liver damage has occurred) – baseline LFTs, and monitor – Hyperglycemia – Gouty arthritis

Question 31

Niacin baseline ___ should be obtained and monitored

Answer 31

LFT

Question 32

Bile Acid Sequestrants MOA

Answer 32

MOA: bind bile acids in the intestine, resulting in | interruption of the reabsorption of bile acids

Question 33

Bile Acid Sequestrants reduction in

Answer 33

Reduction in cholesterol pool lowers intrahepatic cholesterol, promotes synthesis of LDL receptors. Receptors bind LDL from the plasma, causing further reduction in blood cholesterol.

Question 34

Bile Acid Sequestrants reduce

Answer 34

Reduce LDL cholesterol levels

Question 35

Bile Acid Sequestrants used primarliy as adjucts to

Answer 35

Used primarily as adjuncts to statins.

Question 36

Bile Acid Sequestrants use often limited as

Answer 36

side effects – GI (nausea, | bloating, cramping, increase in liver enzymes)

Question 37

Cholesterol Absorption Inhibitor - Ezetimibe

Answer 37

– Impairs dietary and biliary cholesterol absorption at he brush border of the intestines – Most commonly prescribed to lower LDL-C after statins

Question 38

Cholesterol Absorption Inhibitor theraputic use

Answer 38

– Reduces total cholesterol, LDL cholesterol, and apolipoprotein B – Approved for monotherapy and combined use with statins

Question 39

Fibric Acid Derivates (Fibrates) most effective

Answer 39

• Most effective drugs available for lowering TG levels (as | much as 50%

Question 40

Fibric Acid Derivates (Fibrates) can raise

Answer 40

Can raise HDL cholesterol

Question 41

Fibric Acid Derivates (Fibrates) little or no effect

Answer 41

• Little or no effect on LDL cholesterol

Question 42

Fibric Acid Derivates (Fibrates) can increase the risk for

Answer 42

Can increase the risk for bleeding in patients taking | warfarin

Question 43

Fibric Acid Derivates (Fibrates) can increase the risk for

Answer 43

• Can increase the risk for rhabdomyolysis in patients | taking statins

Question 44

Fibric Acid Derivates (Fibrates) three durgs in US

Answer 44

– Gemfibrozil [Lopid] – Fenofibrate [Tricor, others] – Fenofibric acid [TriLipix

Question 45

Fibric Acid Derivates ADR

Answer 45

Adverse effects: have been associated with muscle toxicity and is more profound with those patients also treated with a statin.

Question 46

Fibric Acid Derivates ADR effect can be medicated by

Answer 46

Effect can be mediated by a competitive | inhibition of CYP3A4.

Question 47

Fibric Acid Derivates safer options

Answer 47

Pravastatin and Fluvastatin are NOT extensively metabolized by the CYP3A4 • Maybe safer when combination therapy is required with a fibrate, but this is not certain

Question 48

Fibric Acid Derivates interactions

Answer 48

Interactions – interfere with the metabolism of warfarin (warfarin should be reduced by 30% in these patients).