Exam 1: Lecture 12, Hyperlipidemia

Question 1

what is leading cause of death for most racial/ethic groups in US?

Answer 1

Heart disease

Question 2

Key heart disease risk factors

Answer 2

High BP, High LDL cholesterol, and smoking

Question 3

Lipoproteins

Answer 3

complexes of lipids and proteins that transport lipids through the plasma

Question 4

Hyperlipoproteinemias/hyperlipidemias

Answer 4

metabolic disorders that involve elevations in any lipoprotein species

Question 5

Apolipoproteins

Answer 5

The protein constituents of lipoprotein particles that play a key role in transporting cholesterol, triglycerides, phospholipids, and fat-soluble vitamins between the intestine, liver and peripheral tissues

Question 6

“Good” cholesterol

Answer 6

HDL

Question 7

Statin prototype:

Answer 7

Lovastatin

Question 8

Statin MOA:

Answer 8

Competitive inhibitors of HMG-CoA reductase, which catalyzes an early, rate-limitng step in cholesterol biosynthesis

Question 9

Statins Applications:

Answer 9

Hyperlipidemia

Question 10

Statins Notables:

Answer 10

First pass effect

Drug-Drug interactions related to CYP3A4

Liver toxicity, muscle breakdown (myopathy)

Not for pregnant people, baby needs cholesterol

No grapefruit * 6+/day *

Question 11

Drugs in Statin class?

Answer 11

Lovastatin
Pravastatin
Simvastatin
Rosuvastatin
Atorvastatin

Question 12

High intensity statins?

Answer 12

Lower LDL-C by 50% or more

Atorvastatin 40-80mg
Rosuvastatin 20-40 mg

Question 13

Moderate-intensity statins?

Answer 13

Lower LDL-C by 30% - <50%

A bunch

Question 14

Low-intensity statins?

Answer 14

Lower LDL-C, on average by < 30%

A bunch, lower dose than moderate-intensity

Question 15

MOA Statins detailed

Answer 15

1. Inhibit HMG-CoA reductase, leading to decreased conc of cholesterol within cell
2. Low intracellular cholesterol stimulates the synthesis of LDL receptors
3. Increase number of LDL receptors promotes uptake of LDL from blood
4. Low intracellular cholesterol decreases secretion of VLDL.

Question 16

Clinical Application statins

Answer 16

Intensive statin treatment leads to no change in lumen size but decrease in lipid core.

Will also cause increase in fibrous and calcified tissues

Question 17

Bile acid-binding resins: Prototype

Answer 17

Cholestyramine

Question 18

Bile acid-binding resins: MOA

Answer 18

bind bile acids in GI tract and promote excretion

Question 19

Bile acid-binding resins: Applications

Answer 19

Primary hypercholesterolemia

Question 20

Bile acid-binding resins: Notables

Answer 20

in patients who also have hypertriglyceridemia, VLDL levels may be increased during treatment

Bloating, and effect drug absorption (don’t use if on many other drugs)

Question 21

Drugs in Bile acid-binding resins class?

Answer 21

Cholestyramine

Colestipol

Question 22

Bile acid-binding resins MOA detailed:

Answer 22

Bile acid binding resin will bind to the cholesterol along with bile and cause it to be excreted.

can have GI complications, not 1st line

Question 23

Nicotinic acid: prototype

Answer 23

Niacin (Vitamin B3)

Question 24

Nicotinic acid: MOA

Answer 24

Inhibits VLDL secretion, decreasing production of LDL

Question 25

Nicotinic acid: Applications

Answer 25

Combo with resin or reductase inhibitor will normalize LDL in most patients with heterozygous familial hypercholesterolemia and other forms of hypercholesterolemia

Question 26

Nicotinic acid: Notables

Answer 26

Hepatotoxicity, platelet deficiency, birth defects w/ high dose, tachycardia, flushing, diarrhea, itchiness, dry skin

Question 27

Fibrates: Prototype

Answer 27

Gemfibrozil

Question 28

Fibrates: MOA

Answer 28

Function primarily as ligands for nuclear transcription receptor PPAR-a

up regulate LPL, apo A-I, and apo A-II

down regulate apo C-III (inhibitor of lipolysis)

Question 29

Fibrates: Applications

Answer 29

Hypertriglyceridemias in which VLDL predominate

Question 30

Fibrates: Notables

Answer 30

Stomach aches, gas

** Rare **: rashes, GI symptoms, myopathy, arrhythmias

Question 31

Ezetimibe prototype

Answer 31

Its own prototype

Question 32

Ezetimibe MOA

Answer 32

Inhibits NPC1L1 mediated cholesterol reabsorption

Question 33

Ezetimibe Applications:

Answer 33

Hypercholesterolemia, synergistic with reductase inhibitors

Question 34

Ezetimibe Notables:

Answer 34

Reversible impaired hepatic function, myositis (inflamed muscle)

Question 35

PCSK9 inhibitors

Answer 35

Alirocumab

Evolocumab

Question 36

PCSK9 inhibitors MOA

Answer 36

Bind to PCSK9, inhibiting it from binding to LDL receptor.

This increases the number of LDL receptors available to clear LDL, thereby lowering LDL-c levels.

Normally PCSK9 promotes degradation of receptors

Question 37

Dietary Management of Hyperlipoproteinemia

Answer 37

total calories from fat should be <25%
Saturated fat <7%
Cholesterol <200mg/day

Question 38

What increase VLDL?

Answer 38

Sucrose and fructose

Question 39

Principal factors increasing LDL?

Answer 39

Cholesterol, saturated and trans fats

Question 40

What do Omega 3 fatty acids do?

Answer 40

Activate PPARa = reduce tyiglycerides

Question 41

Lomitapide MOA:

Answer 41

prevents apoB and Triglycerides from coming together and prevents VLDL loading.

Inhibits MTTP

Question 42

Mipomersen MOA:

Answer 42

Mipomersen is an antisense strand that binds to ApoB mRNA

Prevents the translation and synthesis of ApoB-100, causing decrease VLDL, leading to decrease LDL-C

Question 43

Exogenous pathway

Answer 43

internalization of lipids

chlymicron formed, goes into capillaries

LPL releases Free Fatty Acids and returns to liver by engaging with LDLR

Question 44

Endogenous

Answer 44

VLDL with ApoB-100 on it released by liver and goes into capillary

LPL releases FFA and IDL returns to liver or forms LDL which can bind on peripheral tissues

Question 45

value of HDL?

Answer 45

being able to scavenge a lot and in peripheral tissues