Drugs

Question 1

What are statins good at?

Answer 1

Reducing LDL

Question 2

What are fibrates good at?

Answer 2

Reducing triglycerides

Question 3

What is niacin good at?

Answer 3

Increasing HDL

Reducing triglycerides

Question 4

How do statins work?

Answer 4

Inhibition of enzyme (HMG-CoA reductive) has two effects:

(1) decrease liver cholesterol synthesis => inc. LDL receptor expression => dec. LDL and VLDL
(2) decrease liver cholesterol synthesis => dec. liver VLDL production => dec. TG

Question 5

Which statins are the best at lowering LDL?

Answer 5

Atorva, Rosuva

Simva

Question 6

Which statin is the lowest intensity?

Answer 6

Fluva

Question 7

What are some other statin benefits, besides lipid reduction?

Answer 7

Increased endothelial vasodilation

Inc. plaque stability

Dec. inflammation

Dec. lipoprotein oxidation

Dec. platelet aggregation + fibrinogen (less clots!)

Question 8

Why are statins dosed at night?

Answer 8

Period with highest cholesterol synthesis

Question 9

Which statins would be best for AM dosing?

Answer 9

Atorva and Rosuva

Have longer half-lives and will last longer to reach night-time cholesterol synthesis

Question 10

Which statins are prodrugs that get activated in the liver?

Answer 10

Lova

Simva

Question 11

AE’s for statins

Answer 11

Mild: headache, rash, GI upset

Liver dysfunction

Myalgia

Question 12

Statins DDIs

Answer 12

CYP3A4 inhibitors - ex: amiodarone
(Affects lova, simva > atorva&raquo_space;> Prava, rosuva, fluva)

Fibrates

Niacin = 1+ g/day

Bile acid resins

Warfarin

Red yeast rice

Question 13

How do fibrates work?

Answer 13

Activate receptor - PPARalpha

PPAR = peroxisome proliferator-activated receptors

Question 14

How do fibrates work?

Answer 14

PPAR activators

(1) more ffa oxidation => less TG made in liver (less building blocks for VLDL)
(2) Inc. LPL and less apoC made => more clearance of TG-rich lipoproteins = dec. VLDL and TG
(3) More LDL receptors made => dec. VLDL and LDL
(4) Inc. apoA made => more HDL => more reverse chol. Transport

Question 15

What are some other effects fibrates have?

Answer 15

Inc. HDL

Dec. triglycerides

Question 16

Which fibrate is metabolized in the liver and thus contraindicated in hepatic dysfunction?

Answer 16

FENOfibrate (converted to fenofibric acid)

Question 17

What are some adverse effects of fibrates?

Answer 17

GI (nausea, dyspepsia, abdominal pain)

Myopathy

Question 18

What are some DDI’s with fibrates?

Answer 18

Statins => myopathy (avoid with GEMIfibrozil)

Bile acid resins => dec. bioavailability
Take fibrate 1 hour before or 4 hours after

Warfarin => inc. INR

Question 19

When are fibrates contraindicated?

Answer 19

Severe renal or hepatic failure

Pregnancy

Children

Question 20

What is another name for Niacin?

Answer 20

Vitamin B3

Question 21

What sites does Niacin work at?

Answer 21

Adipose tissue

liver

Plasma

Macrophages

Question 22

What effect does niacin have in adipose tissue?

Answer 22

Inhibits adenylyl cyclase => dec. cAMP

=> dec. hormone-sensitive lipase
=> dec. TG lipolysis and FFA release

Question 23

What effects does Niacin have in the liver?

Answer 23

Dec. FFA transport => dec. TG made in liver => less VLDL => dec. TG and LDL

Dec. liver clearance of ApoA in HDL => more HDL in plasma => more reverse cholesterol transport => dec. LDL

Question 24

What effect does Niacin have in plasma?

Answer 24

Increased LPL activity => dec. TG, VLDL, chylomicron

Question 25

What effect does niacin have in macrophages?

Answer 25

Increased scavenger receptor and cholesterol exporter => dec. cholesterol in foam cells

Question 26

What are two metabolites of niacin (and their effects)?

Answer 26

Nicotinuric acid = vasodilation (flushing) Nicotinamide = toxic metabolites for liver

Question 27

What are Niacin adverse effects?

Answer 27

Flushing, headache, itching GI: nausea, dyspepsia, peptic ulcer Dry skin Acanthus nigricans (darkening of skin) Hepatotoxicity Hyperglycemia Myopathy Hyperuricemia

Question 28

What are some Niacin DDIs?

Answer 28

Statins: lower risk with niacin @ less than 1 g/day Bile acid resins: colestipol >>> cholestyramine Separate by 4-6 hours!

Question 29

Niacin is the only drug that does what?

Answer 29

Lower LpA

Question 30

For which patients should Niacin be avoided?

Answer 30

Uncontrolled diabetics Active PUD liver disease Gout

Question 31

What does Ezetimibe do?

Answer 31

Inhibits cholesterol absorption

Question 32

How does Ezetimibe inhibit cholesterol absorption?

Answer 32

Binds cholesterol transporter and leads to decreased dietary and biliary cholesterol uptake Decreased cholesterol in chylomicrons and less delivered to liver Dec. delivery to liver leads to increased production of LDL receptors (which will take up more LDL)...but then that also leads to more cholesterol made in liver from LDL uptake :(

Question 33

What effects does ezetimibe have?

Answer 33

Decreases LDL NO EFFECT on TG or HDL

Question 34

What are some adverse effects of Ezetimibe?

Answer 34

Headache, diarrhea Arthralgia fatigue Cough Inc. serum transaminases Hypersensitivity (rare)

Question 35

What are DDIs associated with Ezetimibe?

Answer 35

Minimal (since not absorbed!) Bile acid resins will decrease Ezetimibe' absorption - take 2 hrs before or 4 hours after BAR Warfarin : may inc. levels Cyclosporine : may inc. levels

Question 36

What's Ezetimibe' relationship with statins?

Answer 36

Additive to decreased LDL by additional percentage

Question 37

What are some bile acid resins (BARs)?

Answer 37

Cholestyramine Colestipol Colesevelam

Question 38

How do BARs work?

Answer 38

In anion exchange resins: Bind bile acids in gut to excrete them in stool => dec. bile acid stores In the liver: Inc. bile acid synthesis with dec. hepatic cholesterol => more LDL receptors made => dec. LDL (from uptake) Dec. cholesterol in liver also increases HMG-CoA reductase activity to increase chol. Synthesis => dec. LDL receptor, Inc. VLDL, Inc. TGs

Question 39

Which BAR would you recommend for a patient with GI upset?

Answer 39

Colesevelam

Question 40

What are adverse effects associated with BARs?

Answer 40

GI intolerance: bloating, dyspepsia, gas, nausea, constipation Gritty slurry from cholestyramine and colestipol Increased TGs (avoid in severe hypertriglyceridemia)

Question 41

What are some BAR DDIs?

Answer 41

Interfere with drug absorption so separate 1 hour before or 3-4 hours after!!! Fluva/Pravastatin Niacin Fibrates Ezetimibe Warfarink, beta-blockers, thiazides, furosemide Propranolol, levothyroxine Vitamins A, D, E, K

Question 42

What effect does Fish oil have?

Answer 42

Inhibits VLDL and TG synthesis in liver

Question 43

What are adverse effects of fish oil?

Answer 43

GI upset, burping, altered taste

Question 44

What are some cons of fish oil?

Answer 44

Does not lower LDL (may actually increase it) No effect on HDL

Question 45

How do PCSK9 inhibitors work?

Answer 45

Prevent PCSK9 from binding to LDL receptors (which would promote their degradation within the liver and result in higher LDL levels in the blood)

Question 46

What are indications for PCSK9 inhibitors?

Answer 46

Familial hypercholesterolemia Clinical atherosclerotic CVD Adjunct to diet and maximally tolerated statin therapy in pts who require additional LDL lowering

Question 47

What are some adverse effects associated with PCSK9 inhibitors?

Answer 47

Hypersensitivity/ injection site reactions Increased liver function tests (Alirocumab) Nasopharyngitis, upper respiratory infection, flu Very low LDL Antibody formation

Question 48

What are some Tx combos?

Answer 48

Statin + Ezetimibe Statin + BAR Niacin + BAR Statin + Niacin + BAR

Question 49

Which combo lowers LDL the least?

Answer 49

Niacin + BAR

Question 50

Which combo lowers LDL the most?

Answer 50

Statin + niacin + BAR