1-6 and 7

Question 1

What type of patient should NOT be prescribed resins (bile acid sequestrants)?

Answer 1

Patient with severe hypertriglyceridemia

Question 2

There is a DDI between resins and what three other drug classes?

Answer 2

Beta blockers, Loop Diuretics, and Thiazide Diuretics

Question 3

What drug class works via charge based interaction?

Answer 3

Bile Acid Sequestrants

Question 4

Bile acid sequestrants are ___ charged while bile acids are ___ charged. Given this, bile-resin complex is eliminated from body via stool.

Answer 4

Bile acid sequestrants are positively charged
Bile acids are negatively charged

Question 5

What compensation occurs due to bile acid sequestrants?

Answer 5

-Increase in LDL receptors

Question 6

What are the three bile acid sequestrants?
(coles in a pool, cole saved a lamb, coles tyrin me out)

Answer 6

1) Colesevelam
2) Colestipol
3) Cholestyramine

Question 7

True or False: Depletion of bile acid is accompanied by a decrease in new bile acid synthesis in the liver

Answer 7

False - Depletion of bile acid is accompanied by an INCREASE in new bile acid synthesis in the liver

Question 8

How does increasing bile synthesis affect hepatic cholesterol content?

Answer 8

Increasing bile synthesis DECREASES hepatic cholesterol content

Question 9

True or False: Colestipol increases hepatic LDL receptor membrane localization and enhances LDL clearance from circulation

Answer 9

True

Question 10

Simvastatin and Atrorvastatin belong to which drug class?

Answer 10

Statins (HMG-CoA Reductase inhibitors)

Question 11

True or False: Simvastatin and Lovastatin are inactive lactones that need to be converted to active forms

Answer 11

True -
Their active forms are simvastatin hydroxy acid and lovastatin hydrox acid

Question 12

Which drug class has extensive first pass metabolism and is regulated by OATP1B1?

Answer 12

Statins (HMG-CoA Reductase Inhibitors)

Question 13

Why is myopathy an AE of statins?

Answer 13

Statins can induce reduction in CoQ10 synthesis

Question 14

Rhabdomyolysis (rapid muscle damage) is an AE associated with which drug class?

What increases one’s risk of developing this?

Answer 14

Statins
Consuming grapefruit (furanocoumarins in grapefruit inhibits CYP, preventing statin metabolism, increasing systemic presence and leading to toxicity)

Question 15

True or False: statins have role in anti-inflammatio/anti-coagulation, decreasing LDL-C levels, and improving endothelial function

Answer 15

True

Question 16

Inhibition of HMG CoA results in increased expression of which gene?

Answer 16

LDL receptor gene

Question 17

Statins cause reduced synthesis of cholesterol within cells. As a result of this, __ proteins (found in ER and Golgi) are cleaved by ___, leading proteins to be translocated into the nucleus.

Answer 17

SREBP (sterol responsive element binding protein)

Site Proteases (S1P, S2P)

Question 18

How does the presence of SREBP in the nucleus affect LDL receptor gene?

Answer 18

Leads to increase in LDL receptor genes, thereby causing more LDL receptors on surface of cell, which aid in removing LDL cholesterol from blood

Question 19

Prior to being secreted into the plasma, where is Apo-A1 made?

Answer 19

Liver

Question 20

When ApoA-I and phospholipid interact with each other (via RCT), they form what two HDL molecules?

Answer 20

1) Nascent HDL (Pre-B1-HDL)
2) Nascent Discoidal HDL (ndHDL)

Question 21

In reverse cholesterol transport, cholesterol is effluxed by receptors like ___, ___, or ___

Answer 21

ABCA1, ABCG1, SR-B1

Question 22

In reverse cholesterol transport, the nascent HDL absorbs free cholesterol in circulation and converts them to cholesterol esters via ____, and enzyme.

Answer 22

LCAT (lectin-cholesterol acetyltransferase)

Question 23

As nascent LDH accumulates more cholesterol ester, it grows in sizes and matures, becoming ___ and ___ particles (also known as a1-4 particles)

Answer 23

HDL 3 and HDL 2 particles

Question 24

Which enzyme is the rate limiting one involved in the step of Reverse Cholesterol Transport whereby HDL size increases?

Answer 24

PLTP (Phospholipid transfer protein)

Question 25

LCAT converts pre-B-1 (nascent LDH) to ___ PLTP converts HDL3 to ___

Answer 25

HDL3; HDL2

Question 26

True or False: As ApoA1 containing particles mature, they try to intake as many TG particles as possible

Answer 26

True

Question 27

Which protein helps in the exchange of cholesterol ester (CE) and triglyceride particles (TG) between HDL and ApoB100 (VLDL and LDL) containing lipoprotein particles?

Answer 27

CETP (cholesterol ester transfer protein)

Question 28

Once cholesterol esters are taken up by VLDL and LDL, they are transferred back to the liver via ___ receptor. Cholesterol esters will be broken down and made to make bile.

Answer 28

LDL - receptor

Question 29

____: pathway that transports cholesterol from extrahepatic tissues (vessel wall) to the liver and intestines for recycling and excretion

Answer 29

Reverse Cholesterol Transfer

Question 30

What are the two principal mediators for reverse cholesterol transport?

Answer 30

HDL (high density lipoprotein) ApoA-I (the apoprotein associated with HDL)

Question 31

True or False: HDL levels in body can help assess efficiency of RCT and cholesterol efflux out of vessel walls

Answer 31

True

Question 32

True or False: LDL is primarily involved with removing cholesterol from atherosclerotic plaques, back into the liver, and finally into bile

Answer 32

False - primarily mediated by HDL

Question 33

Why is HDL considered 'good' cholesterol? Why is LDL considered 'bad' cholesterol?

Answer 33

HDL: REMOVES cholesterol from blood/artery walls LDL: DEPOSITS cholesterol between layers in artery wall and STARTS process of atherosclerosis

Question 34

_____is formed by bridging of Apo B 100 (containing LDL) and Apo A via: disulfide bond and is a NOVEL BIOMARKER FOR CV DISEASE AND ATHEROSCLEROSIS

Answer 34

Lipoprotein (a) (levels greater than 75 nmol/L are considered risk factors)

Question 35

What gene mutation can lead to hyperlipidemia?

Answer 35

Mutation in LPL (lipoprotein lipase) in infancy or childhood

Question 36

HDL is a ___ containing lipoprotein

Answer 36

Apo A

Question 37

Liver derived VLDL and LDL lipoproteins are ____ containing lipoproteins

Answer 37

Apo B-100

Question 38

Diet or gut derived lipoproteins are chylomicron ______ containing lipoproteins

Answer 38

Apo B-48

Question 39

What happens if apoprotein (acts as ligand) is not located on lipoprotein surface, as it normally is?

Answer 39

Particles are not taken up by liver

Question 40

What is found within a lipoprotein?

Answer 40

1) Triglycerides 2) Cholesterol esters

Question 41

What is found on surface of lipoprotein?

Answer 41

1) Apoprotein 2) Cholesterol

Question 42

Chylomicrons are lipoproteins formed in the ____ following dietary fat intake

Answer 42

intestine

Question 43

VLDL is the lipoprotein produced from the __

Answer 43

liver

Question 44

True or False: Both VLDL and chylomicrons contain triglycerides that undergo breakdown with aid of LPL (lipoprotein lipase) and HL (hepatic lipase) to release free fatty acids

Answer 44

True

Question 45

The breakdown products or remnants of lipoprotein particles are taken up by the liver through mediation of ___ and ___, which act as ligands

Answer 45

Apo B and Apo E

Question 46

Exogenous dietary lipids are processed by the intestine to ___ particles Endogenouos lipoproteins are synthesized by the ___ in the form of ____ particles

Answer 46

Exogenous - chylomicron particles Endogenous - liver; VLDL

Question 47

Cholesterol Synthesis Pathway is also known as ___ Pathway

Answer 47

Mevalonate Pathway

Question 48

_____ is the rate limiting enzyme for cholesterol synthesis in the Mevalonate Pathway

Answer 48

HMG-CoA Reductase

Question 49

___ is also known as pyridine-3-carboxylic acid

Answer 49

Niacin

Question 50

True or False: Niacin belongs to the water soluble B-complex vit family and posses vitamin property only in carboxyl form

Answer 50

False - only in amide form

Question 51

True or False: Niacin shows anti-hyperlipidemic effects only at lower doses

Answer 51

False - Niacin shows anti-hyperlipidemic effects only at HIGHER doses

Question 52

How does Niacin affect: LDL-C, HDL-C, and triglycerides?

Answer 52

LDL-C, cholesterol: Decreases HDL-C: Increases

Question 53

Niacin acts through the niacin 1/2 receptor, also known as the hydroxycarboxylic acid receptor or GPR ___ A and B

Answer 53

GPR 109 A/B

Question 54

True or False: Niacin belongs to GPCR family

Answer 54

True

Question 55

How does niacin (nicotinic acid) prevent TG (adipose) from being converted to free fatty acids in the liver? (hint: what enzyme is inhibited?)

Answer 55

Inhibits HSL (hormone sensitive lipase) in adipose tissue -thereby: blocking conversation of TF to FFA in the liver

Question 56

True or False: As a result of niacin, there is decrease breakdown of TG to free fatty acids

Answer 56

True

Question 57

What enzyme does Niacin inhibit?

Answer 57

HSL (hormone sensitive lipase)

Question 58

How does Niacin promote clearance of chylomicrons and VLDL triglycerides?

Answer 58

Enhances LPL activity

Question 59

How does Niacin affect Apo AI content in plasma?

Answer 59

Niacin increases Apo-A-1 content within the plasma

Question 60

True or False: In monocytes/macrophages, niacin enhances the cholesterol efflux process by up-regulating efflux transporter (e.g ABCA1)

Answer 60

True

Question 61

Flushing and dyspepsia are an AE associated with which anti-hyperlipidemic drug? What worsens flushing?

Answer 61

Niacin -Caffeine use + Niacin

Question 62

The most important and serious AE with niacin use is ____, as observed with elevated AST/ALT

Answer 62

hepatotoxicity

Question 63

Niacin can increase hepatic gluconeogenesis, leading to the _____, an AE.

Answer 63

hyperglycemia

Question 64

Mechanism for flushing AE in niacin use?

Answer 64

1) The niacin receptor mediates the release of arachidonic acid, produces PGE2/PGD2 2) PGE2 and PGD2 acts on DP1/EP2/EP4 receptors in VSM 3) Vasodilation and redness

Question 65

Contraindication for niacin use?

Answer 65

Diabetic

Question 66

What is the major niacin metabolite?

Answer 66

Nicotinuric acid (non-toxic metabolite of nicotinic acid)

Question 67

What class of anti-hyperlipidemic drugs do fenofibrate and gemfibrozil belong to?

Answer 67

The Fibrates (PPAR alpha agonists)

Question 68

What receptors to the Fibrates act on?

Answer 68

PPAR's (Peroxisome Proliferator-Activated Receptors)

Question 69

Where do Fibrates act?

Answer 69

Liver and Adipose Tissue

Question 70

When a fibrate binds to PPAR, it promotes heterodimerization of PPAR (nuclear receptor) with ____. This leads the heterodimer complex to bind to the ____, changing gene regulation

Answer 70

RXR (retinoid x receptor) PPRE (responsive element)

Question 71

What three genes do PPAR alpha agonists (fibrates) upregulate?

Answer 71

1) LDL receptor 2) Apo CII 3) Apo A1

Question 72

When two genes do PPAR alpha agonists down regulate?

Answer 72

1) Apo C111 (inhibits LPL) 2) IL-6

Question 73

Gemfibrozil has major interaction with which drug class?

Answer 73

Statins - prevents uptake of statins in liver - interferes with OATP1B1 transporter mediated statin uptake

Question 74

Statins/gemfibrozil compete for same enzyme, _____, for metabolism

Answer 74

Glucoronosyl transferase

Question 75

If gemofibrozil is given with statins, both of their plasma levels will increase. Elevated statin level can lead to the AE of ___

Answer 75

myopathy

Question 76

True or False: Both Gemofibrozil and Fenofibrate have major drug interactions with statins

Answer 76

False - Fenofibrate has NO major drug interactions with statins (no myopathy)

Question 77

True or False: Fibrates are ok for kids to take

Answer 77

False - NOT ok

Question 78

Where is PCSK9 (proprotein convertase subtilisin/kexin 9) highly expressed/formed prior to being secreted into bloodstream?

Answer 78

Kidney, liver, intestine

Question 79

True or False: PCSK9 is localized intracellularly

Answer 79

False - PCSK9 is localized EXTRACELLULARLY

Question 80

____ are antibodies and inhibit PCSK9 activity

Answer 80

PCSK9 Inhibitors

Question 81

What are the two PCSK9 inhibitors? (hint: evolution and ally rows + -cumab)

Answer 81

1) Evolocumab 2) Alirocumab

Question 82

How do PCSK9 inhibitors increase LDL receptors in membrane?

Answer 82

Inhibiting PCSK9 prevents PCSK9 mediated LDL receptor degradation in lysosomal system

Question 83

True or False: PCSK9 Inhibitors increase membrane LDL receptors and increase LDL-C clearance from plasma

Answer 83

True

Question 84

___ is a siRNA targeting PCSK9 mRNA, resulting in degradation of PCSK9 mRNA and limiting PCSK9 protein synthesis

Answer 84

Inclisiran

Question 85

Which drug inhibits dietary cholesterol uptake?

Answer 85

Ezetimibe

Question 86

Where does Ezetimibe act?

Answer 86

Intestinal lumen

Question 87

How does Ezetimibe inhibit luminal cholesterol uptake by jejunal enterocytes? (hint: what receptor does it block)

Answer 87

Blocks NPC1L1 - cholesterol transport protein

Question 88

True or False: Ezetimibe reduces 1) cholesterol content for intestinal chylomicron synthesis and 2) delivery of cholesterol load into liver as chylomicron remnants

Answer 88

True

Question 89

What is a secondary benefit of Ezetimibe?

Answer 89

As cholesterol delivery to liver decreases, liver makes more LDL receptors

Question 90

___ blocks NPC1L1 present in enterocytes of intestine (mostly jejenum)

Answer 90

Ezetimibe

Question 91

What drug class does Lomitapide belong to?

Answer 91

MMTP (microsomal triglyceride transfer protein) Inhibitors

Question 92

Lomitapide binds to ____ in the ER, preventing packaging/assembly of ___ containing lipoprotein bodies, which include both ___ (enterocytes) and VLDL-C____(hepatocytes)

Answer 92

MTTP; ApoB; ApoB48 (enterocytes); VLDL-C-ApoB100 (hepatocytes)

Question 93

Major AE with MTTP Inhibitors?

Answer 93

Hepatic toxicity

Question 94

What are the active ingredients in omega-3 fatt acid?

Answer 94

EPA and DHA (Lovaza, Omytrg)

Question 95

How does omega-3 act as a anti-inflammatory drug?

Answer 95

Prevents formation of AA

Question 96

The DHA (omtryg) component in omega 3 supplements are known to increase ___ levels

Answer 96

LDL-C levels

Question 97

Vascepa contains only one of the active ingredients in omega-3 fatt acids - which one?

Answer 97

Vascepa contains EPA component only

Question 98

What are the benefit of using vascepta?

Answer 98

Since it only contains EPA (active ingredient in omega 3 fatty acids) - it does NOT increase LDL-C (as DHA component does)

Question 99

True or False: Vascepa/Icosapent Ethyl prevents plaque formation/inflammatory responses, improves endothelial function, and inhibits platelet aggregation

Answer 99

True

Question 100

What is a newer agent for treating hyperlipidemia?

Answer 100

1) Bempedoic Acid 2) Evinacumab

Question 101

How does Bempedoic Acid, a newer agent for treating hyperlipidemia, decrease cellular cholesterol synthesis?

Answer 101

Inhibits ATP Citrate Lyase, the enzyme involved in synthesizing Acetyl-CoA

Question 102

True or False: Bempedoic Acid is a prodrug that needs to be activated in hepatic tissue

Answer 102

True

Question 103

Clinical indication for Bempedoic Acid use?

Answer 103

Heterozygous Familial Hypercholesterolemia or persistent, long term atherosclerotic CVD

Question 104

True or False: Bempedoic Acid is very effective at lowering blood LDL-C levels

Answer 104

True

Question 105

True or False: Bempedoic Acid can be used as an adjunct to diet and max. tolerated statin therapy

Answer 105

True

Question 106

There is a DDI with Bempedoic Acid and ___, leading to higher incidences of ___

Answer 106

statins; myopathy

Question 107

More than _ mg of Simvastatin and _ mg of Pravastatin should be avoided

Answer 107

20 mg ; 40 mg

Question 108

What anti-hyperlipidemia drug causes a rise in blood uric acid levels?

Answer 108

Bempedoic Acid

Question 109

____ can be administered in combination with Ezetimibe

Answer 109

Bempedoic Acid

Question 109

____ is a recombinant IgG4 monoclonal antibody that targets antiopoietin-like protein 3 (ANGPTL3)

Answer 109

Evinacumab

Question 110

What drug is approved to be an adjunctive therapy for homozygous familial hypercholesterolemia (HoFH)

Answer 110

Evinacumab

Question 111

Evinacumab bind and blocks_____, an angiopoietan-like protein, thereby sparing LPL/EL activity, improving triglyceride breakdown, and reducing LDL-C levels

Answer 111

ANGPTL3