Lipid Lowering Drugs

Question 1

Density: What lipoprotein sinks?

Answer 1

HDL, it is protein-rich

Question 2

Density: What lipoprotein floats?

Answer 2

Chylomicrons and VLDL. Fat floats and these are triglyceride rich

Question 3

Density: What lipoprotein floats?

Answer 3

Chylomicrons and VLDL. Fat floats and these are triglyceride-rich

Question 4

Liver _____ drives reverse cholesterol transport in macrophages

Answer 4

SR-BI

Question 5

Who discovered Mevastatin?

Answer 5

Dr.Akira Endo

Question 6

Who discovered Lovastatin?

Answer 6

Dr. P.Roy Vagelos

Question 7

Who created simvastatin?

Answer 7

Dr.P.Roy Vagelos

Question 8

What is the MOA of statins?

Answer 8

-Overall: reduction of LDL
-Reduces HMG-CoA to mevalonate
-Affects blood cholesterol levels by inhibiting hepatic cholesterol synthesis, thus increasing expression of LDL receptor gene
-Reducing hepatic production of VLDL/LDL the precursors of LDL

Question 9

What is the half-life of statins?

Answer 9

1-4 hours

Question 10

When is most hepatic cholesterol synthesis done?

Answer 10

Between midnight to 2 am

Question 11

When should you take a statin medication?

Answer 11

In the evening

Question 12

What is the half-life of atorvastatin and rosuvastatin?

Answer 12

Approx 20 hours

Question 13

What is the half-life of simvastatin?

Answer 13

5 hours

Question 14

When is the peak plasma concentration of statins exhibited?

Answer 14

1-4 hours

Question 15

What percentage of statins are eliminated in the feces?

Answer 15

> 70%

Question 16

Therapeutic Effects of statins: When do they exhibit the maximal effect on plasma cholesterol? (answer is in days)

Answer 16

7-10 days

Question 17

Are statins effective for hoFH patients?

Answer 17

NO

Question 18

What are the adverse effects of statins?

Answer 18

Hepatotoxicity and Myopathy (muscle weakness)

Question 19

What is the MOA of bile acid sequestrants?

Answer 19

-Depletion of bile acid, decreases re-absorption )via enterohepatic circulation)
-Increases hepatic synthesis of bile acids
-Increases LDL receptor number, decreases plasma LDL-C

Question 20

Do bile acid sequestrants work the same no matter the dosage?

Answer 20

No, they are dose dependant

Question 21

What formulations can you have for bile acid sequestrants?

Answer 21

-Powder mixed with juice/water
-tablets
-capsules

Question 22

Adverse reactions to bile acid sequestrants:

Answer 22

-bloating, dyspepsia, constipation
-Reduction of plasma levels of lipid-soluble vitamins (A,E,D,K)

Question 23

What is the MOA for Niacin in adipose tissue and in hepatic tissue?

Answer 23

In adipose tissue: inhibits the lipolysis of TG by inhibiting hormone-sensitive lipase (HSL) and decreasing free fatty acids
In hepatic tissue: it decreases esterification of TG, increasing ApoB-100 degradation, decreasing VLDL
It also enhances LPL activity by increasing clearance of both chylomicrons and VLDL

Question 24

What effect does Niacin have on lipoprotein levels?

Answer 24

• 2-6g/day reduces TG by about 35-50%, with maximal effect in 4-7 days
• 4.5-6g/day reduces LDL-C level by about 25%, with maximal effect in 3-6 weeks
  -Increases HDL-C by about 30-40%

Question 25

When is the peak plasma concentration of niacin seen?

Answer 25

30-60 mins

Question 26

What is the half-life of niacin?

Answer 26

60 mins

Question 27

What is the therapeutic use of niacin?

Answer 27

It is indicated for hypertriglyceridemia and elevated LDL-C

Question 28

What forms of niacin are there?

Answer 28

-regular tablets -ER tablets

Question 29

What are the adverse effects of niacin?

Answer 29

-Flushing -Dyspepsia -Hepatotoxicity: increased AST, ALT -Hyperglycemia -Reactive gout: increase uric acid

Question 30

What is the MOA of fibrate derivatives?

Answer 30

-Interaction with PPAR alpha affecting gene expression -Increases lipo-protein lipase which breaks down free fatty acids, decreasing TG-rich VLDL in blood -Increases HDL concentration by increasing Apo-A-I and A-II synthesis

Question 31

Should fibrates be taken with or without food?

Answer 31

With

Question 32

When is the peak plasma concentration of fibrates?

Answer 32

1-4 hours

Question 33

What is the half-life of gemfibrozil and fenofibrate?

Answer 33

Gemfibrozil- 1.1 hours Fenofibrate- 20 hours

Question 34

Where are fibrates concentrated to in the body?

Answer 34

Liver, kidney, intestine

Question 35

What is the dosing of gemfibrozil?

Answer 35

600mg BID, 30 mins before meals

Question 36

Fibrates are the drug of choice for treating hyperlipidemia individuals with type __ hyperlipoproteinemia

Answer 36

3

Question 37

What adverse effects do fibrates have?

Answer 37

GI upset, rash, urticaria, hair loss, muscle pain, fatigue, headache

Question 38

What drugs do fibrates interact with?

Answer 38

Statins

Question 39

What is an example of a cholesterol absorption inhibitor?

Answer 39

Ezetimibe

Question 40

What is the MOA of cholesterol absorption inhibitors

Answer 40

Inhibit NPC1L1 protein on the GI tract epithelial cells as well as hepatocytes. This blocks formation of clathrin AP2 cargo complex involved in trafficking cholesterol Lowering circulating cholesterol to the liver Increases LDL-R to remove circulating LDL

Question 41

Are cholesterol absorption inhibitors first, second, or third line agents to lower LDL?

Answer 41

Second line together with statins

Question 42

What does PCSK9 protease do?

Answer 42

PCSK9 binds to LDL receptor on the surface of the hepatocytes and enhances lysosomal degradation of the LDL receptor,

Question 43

Do PCSK9 inhibitors decrease LDL, HDL, VLDL, or chylomicrons?

Answer 43

LDL

Question 44

Who can use PCSK9 inhibitors?

Answer 44

They can be used alongside diet and maximum statin therapy in adult patients with hoFH and heFH or established ASCVD requiring additional LDL lowering

Question 45

What is a drawback to PCSK9 inhibitors?

Answer 45

They are very expensive

Question 46

What are the two PCSK9 inhibitors?

Answer 46

Evolocumab and Alirocumab

Question 47

What is the dosing of Evolocumab?

Answer 47

140mg Injection biweekly or 420mg once monthly

Question 48

What is the half life of Evolocumab?

Answer 48

11-20 days

Question 49

What is the Evolocumab and Alirocumab dosing for a patient with hoFH?

Answer 49

Evolocumab: 420mg monthly or biweekly Alirocumab: (75mg or 150mg) once every 2 weeks

Question 50

Adverse effects of PCSK9 inhibitors:

Answer 50

Risk of infections such as nasopharyngitis, UTI, or upper respiratory infection is increased

Question 51

Inclisiran is a ____

Answer 51

New PCSK9 inhibitor

Question 52

How many doses a year are required for Inclisiran?

Answer 52

2

Question 53

What is the MOA of Omega-3 fatty acids?

Answer 53

Reduces the production of TG in the liver and enhances clearance of TG from circulating VLDL

Question 54

Whats the half-life of Omega-3 fatty acids?

Answer 54

50-80 hours

Question 55

Adverse effects of Omega-3 fatty acids:

Answer 55

arthralgia nausea fishy burps dyspepsia increased LDL prolonged bleeding time

Question 56

What is the MOA of inhibitors of MTP (microsomal triglyceride transfer protein)

Answer 56

Inhibit TG rich lipoprotein Decrease TG and chlymicrons

Question 57

Should inhibitors of MTP be administered with food?

Answer 57

No, but they should be administered with water

Question 58

What are inhibitors of MTP metabolized by?

Answer 58

CYP 450 enzymes

Question 59

What are the adverse effects of MTP inhibitors?

Answer 59

Diarrhea Vomiting Abdominal pain Hepatotoxicity and liver steatosis

Question 60

What is the MOA of ApoB-100 synthesis inhibitors?

Answer 60

They bind to the mRNA of apo B-100 which breaks down the mRNA and reduces expression of the ApoB-100 protein Therefore, decreasing VLDL

Question 61

What is the recommended dose of ApoB-100 synthesis inhibitors?

Answer 61

1mL of 100mg/ml solution, injected subcut. once weekly

Question 62

What is the half-life of ApoB-100 synthesis inhibitors?

Answer 62

1 to 2 months

Question 63

What are adverse effects of ApoB-100 synthesis inhibitors?

Answer 63

Injection site reactions, including erythema, pain, itching and hematoma Flue like symptoms such as fatigue and headache

Question 64

What is the MOA of LDL apheresis?

Answer 64

Pumps patient blood into. a column using affinity chromatography with an antibody to recognize ApoB-100, LDL is decreased, and blood returned to patient's body