Anti-Hyperlipidemic Drugs

Question 1

Statins inhibit __________.

Answer 1

3-hydroxy-3-methylglutaryl-CoA Reductase (HMG-CoA Reductase)

Question 2

Statins lower the risk of ________.

Answer 2

Arteriosclerotic coronary vascular disease (ASCVD).

Question 3

4 Scenarios in which you would take Statins:

Answer 3

1) Clinical manifestations of cardiovascular disease (MI, angina, etc.).
2) LDL > 190 mg/ dL (normal is 100).
3) Diabetic pt between the ages of 40-75 with LDL between 70-189.
4) LDL between 70-189 and a 7.5% risk of getting atherosclerotic disease.

Question 4

Things that estimate the risk of ASCVD.

Answer 4

HDL levels
Total cholesterol
Systolic blood pressure
Use of meds that lower BP
Diabetes and smoking status
Age, gender, race

Question 5

The most highly prescribed medication by class in the US are:

Answer 5

Lipid regulators/statins.

Question 6

How does HMG-CoA Reductase work?

Answer 6

Synthesizes cholesterol in the liver.

Question 7

How do statins work?

Answer 7

Inhibit HMG-CoA Reductase so that cholesterol is not made in the liver.

Question 8

Statins inhibit cholesterol synthesis in a _______-dependent manner.

Answer 8

dose

So the lowest dose statin should be prescribed.

Question 9

Statins are what type of inhibitor?

Answer 9

Competitive

Question 10

Statins are known for their long ___________.

Answer 10

half-lives.

Question 11

Two examples of Statins

Answer 11

Lipitor (atorvastatin)

Zocor (simvastatin)

Question 12

The reduction in ASCVD risk from statin therapy is related to the degree by which _______ is lowered.

Answer 12

LDL-C

Question 13

Most effective drug for lowering LDL Cholesterol.

Answer 13

Statins

Question 14

Statins reduce LDL cholesterol by what percent?

Answer 14

18-55%

Question 15

Statins reduce the risk for __________ and ________.

Answer 15

Coronary artery disease; stroke

Question 16

Some statins are metabolized by ________.

Answer 16

CYP3A4

Question 17

Adverse effects of statins/CYP3A4 induction.

Answer 17

Myopathy and Rhabdomyolysis

Question 18

When should statins NOT be used?

Answer 18

If pregnant –> pregnancy Category X.

Question 19

Side effect of rhabdomyolysis in statin use.

Answer 19

Muscle cells are broken down, and Myoglobin in released.

The Myoglobin gets into the blood, and is filtered and trapped in the kidney, where it causes kidney failure.

Question 20

These drugs can inhibit cholesterol synthesis in the fetus.

Answer 20

Statins

Question 21

Of the two side effects of statins, which is more common?

Answer 21

Myopathy (10-20% of patients).

Rhabdomyolysis is seen in less than 0.005% of patients.

Question 22

INCREASES HDL levels more effectively than any other drug.

Answer 22

Niacin (nicotinic acid)

Question 23

Good cholesterol

Answer 23

HDL

Question 24

Bad cholesterol

Answer 24

LDL

Question 25

There’s no clear use for this drug b/c of its toxicity profile and lack of efficacy.

Answer 25

Niacin (Nicotinic Acid)

Question 26

3 Non-Statin Drugs that lower LDL levels

Answer 26

1) Ezitimibe
2) BAS
3) PCSK9 Inhibitors

Question 27

Ezitimibe MOA

Answer 27

Prevents the absorption of cholesterol from the small intestine, so it causes the liver to absorb more LDL-C from the blood.

Question 28

BAS

Answer 28

Bile Acid Sequestrant

Question 29

PCSK9 Inhibitors MOA

Answer 29

Accelerates the clearance of LDL’s.

Question 30

Ezetimibe is sometimes combined with this drug to lower LDL levels even more, and together they have shown to reduce the risk of heart attack and stroke.

Answer 30

Simvastatin (Zocor)

Question 31

What are bile acids made from?

Answer 31

Cholesterol!

Question 32

MOA of Bile Acid Sequestrants

Answer 32

They bind bile acids, so the liver responds by making more, and in order to do so it takes LDL-Cholesterol out of the blood.

Question 33

The liver uses _________ to make bile acids.

Answer 33

Cholesterol

Question 34

The name of a BAS.

Answer 34

Colesevelam (Welchol)

Question 35

Why is Colesevalam not indicated for hypertriglyceridemia?

Answer 35

Because they have elevated total cholesterol, but their LDL-C may be low or normal.

Question 36

Used to treat hypertriglyceridemia.

Answer 36

Fibrates

Question 37

Example of a fibrate drug.

Answer 37

Fenofibrate

Question 38

Fenofibrate MOA

Answer 38

Causes lipoprotein lipase to quickly get rid of triglyceride-rich lipoproteins by the liver.

Question 39

PCSK9 Inhibitor MOA

Answer 39

Increases LDL clearance by the liver.

Question 40

These drugs are monoclonal antibodies.

Answer 40

PCSK9 Inhibitors.

Question 41

PCSK9 Inhibitors MOA

Answer 41

These monoclonal antibodies bind PCSK9, preventing it from binding to the LDL Receptor-Cholesterol complex.
So just the LDL Receptor and LDL get endocytosed, and many of the receptors get RECYCLED to the cell surface, and more LDL-C are bound from the blood.

Question 42

PCSK9 Inhibitors

Answer 42

Prevent PCSK9 binding to the LDL-Receptor, allowing LDL-Receptor recycling.

Question 43

Endings of PCSK9 Inhibitor drugs.

Answer 43

“mab” –> Monoclonal antibody.

Question 44

Aliroumab and Evolocumab

Answer 44

PCSK9 Inhibitor drugs

Question 45

Drugs interactions to be aware of with Anti-hyperlipidemics.

Answer 45

Interactions with CYP3A4 inhibitors.

Because some statins are broken down by CYP3A4.