Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

CV Block > Dyslipidemia Drugs > Flashcards

Dyslipidemia Drugs Flashcards

1
Q

2 major sequelae of hyperlipidemia:

A

Pancreatitis - in people with severe hyperlipidemia

Atherosclerosis - most common

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What lipoproteins contain Apo B-100, and where is this protein synthesized?

A

LDL
IDL
VLDL
Lp(A)

Apo B-100 is synthesized in the liver.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Apoprotein B-48 is formed where and found on what type of particle?

A

Apo-B48 is formed in the intestine and found on Chylomicrons.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

LDL is formed from what particle?

A

VLDL

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

HDL contains what apoprotein?

A

A-1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Chylomicrons carry what type of triglyceride? Where does it carry them? What receptor does it bind?

A

Chylomicrons carry dietery triglycerides, and esterified/unesterified cholesterol.

It carries them to peripheral tissues, in a pathway shared by VLDLs, that involved HYDROLYSIS of CHOLESTEROL ESTERS via LPL (Lipoprotein Lipase).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

After going through the bloodstream and through tissues, what happens to chylomicron remnants?

A

They are taken up by the liver.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Describe what VLDLs do.

A

VLDLS are secreted by the LIVER and export TGs to peripheral tissues, where they’re hydrolyzed by LDL in the fat and muscle.

AS TGs get depleted, VLDLs turn into IDL (intermediate density lipoproteins), some of which undergo endocytosis by the liver. The remainder of VLDLs are converted to LDL by further removal of TGs mediated by Hepatic Lipase.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What 2 proteins do VLDLs get from HDL once they are secreted from the liver?

A

Apo E and Apo C

The only way to get these is through HDL

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

LDL is taken up by the liver via LDL receptors. What part of the LDL particle does an LDL receptor bind?

A

Apo B-100

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Under normal Physiological circumstances, what regulates HMG-Co-A Reductase?

A

Cellular Cholesterol level. If intracellular stores are low, HMG-CoA Reductase is active, causing increased synthesis of cholesterol.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How does the liver get rid of all the cholesterol it takes in?

A

Bile secretion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is Lipoprotein A?

A

Formed from LDL and ‘A’ protein, linked via a disulfide bridge.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

HDL is secreted by….

A

The liver and intestines.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

How are HDL particles formed?

A

Free cholesterol is transported from peripheral cell membranes via an ABCA1 transporter on baby HDL particles. These are then esterified via LCAT (lecithin:cholesterol acyltransferase) in the HDL particle, forming a larger HDL species. Choesterol is also delivered to larger HDL particles from macrophages via ABCG1 transporters. (aids in shrinking atherosclerotic plaques)

These cholesterol esters are then trasnferred to VLDL, IDL, and LDL particles with the aid of CETP.

Result is lipid transfer from the periphery to the liver, where it can be excreted.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What receptor on the liver binds directly to HDL?

A

SR-B1 –> accepts cholesterol directly from the HDL particles without the LDL particle mediators.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

At what blood level is LDL clearance saturated? What happens if LDL levels exceed this?

A

700 mg/dL

Above this = acute pancreatitis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Name some characteristics of metabolic syndrome.

A 
Hypertriglyceridemia
Hypertension
Low HDL
Insulin Resistance
Abdominal Obesity 
Male( increased risk factor)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

At what point are chylomicrons supposed to be cleared from your bloodstream?

A

When you’ve fasted for 10 hours.

People with the recessive traits of LPL deficiency or Apo-C2 deficiency have levitated chylomicrons even after a 10 hour fast.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What effect does estrogen have on lipids?

A

Estrogen stimulates VLDL production, and pregnancy automatically causes triglyceridemia, despite dietary restriction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Define mixed lipemia.

A

A combo of elevated VLDLs and Chylomicrons in the bloodstream

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What is deficient in Primary Chylomicronemia? What is elevated in the blood?

A

LPL or Apo-C2 deficiency (Apo-C2 is the co-receptor for LPL)

Chylomicrons and VLDLs are elevated.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

T/F: VLDLs and Chylomicrons compete for LPL binding.

A

TRUE

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What happens in Familial Dysbetalipoproteinemia?

A

remnants of Chylomicrons and VLDLs accumulate, but LDL levels DECREASE.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Family Hypercholesterolemia is inherited how?

A

Au Dominant

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What is the mechanism of familial hypercholesterolemia?

A

Increased LDL, due to defects in the liver LDL receptor.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What is a xanthoma? (This occurs in tons of these hereditary disorders….)

A

an irregular yellow patch or nodule on the skin, caused by deposition of lipids.

In other words, the lipids accumulate under the skin and you can see it

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What is the Defect in Familial Ligand-Defective Apolipoprotein B-100?

A

There is a defect in the Apo-B-100 domain that binds to the LDL receptor in the liver, preventing the uptake of LDLs.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

WHen a person has elevated lipids, what is your first go-to move?

A

Dietary restriction and exercise, unless the patient has evident coronary or peripheral vascular disease.

30
Q

In patients with primarily elevated VLDL, what lifestyle changes will you advise?

A

Synthesis and secretion of VLDL is induced by EXCESS CALORIES (not type of food).

Weight reduction, caloric restriction, and alcohol avoidance.

31
Q

Why avoid alcohol?

A

Alcohol increases VLDL secretion from the liver

32
Q

What do Omega-3 -FA’s do?

A

Activate Peroxisom Proliferator-activated Receptor-alpha (PPAR-a) and induce profound reduction of TGs in some patients.

Also are anti-inflammatory and anti-arhythmic.

33
Q

What type of drugs are specifically formulated to lower LDL cholesterol?

A

HMG-CoA Reductase Inhibitors –> STATINS

34
Q

Name the 2 statins that have to be bioactivated, and their site of bioactivation.

A

Lovastatin and Simvastatin are hydrolyzed in the GI tract to their active B-hydroxyl derivatives.

35
Q

HMG-CoA is the immediate precursor of what component, necessary for the synthesis of cholesterol?

A

Mevalonate.

36
Q

Which Statin is almost 100% absorbed from the GI tract, while the others have 40-75% absorption?

A

Fluvastatin

37
Q

How are Statins metabolized?

A

They undergo first pass metabolism in the liver, then 80% is excreted through the kidneys, and the other 20% is secreted through the bile.

38
Q

What is the MOA of statins?

A

HMG-CoA Reductase mediates the first committed step in cholesterol biosynthesis. The active forms of statins are structural analogs of the HMG-CoA Intermediate formed by the Reductase enzyme.

  1. Cause increase in high affinity LDL receptors - increased uptake of LDL –> reduced blood levels of LDL
  2. Decreased oxidative stress on vasculature - PREVENTS PRENYLATION OF RHO (Rho activates Rab, which mediates many vascular events…)
  3. Anti-inflammatory effects on vasculature
  4. Increase the stability of atherosclerotic plaques
39
Q

A woman is pregnant. Do you give her a statin?

A

No.

Not for use in women pregnant, lactating, or those who may become pregnant.

40
Q

Which statin is the best for SEVERE hypercholesterolemia?

A

ROSUVASTATIN

41
Q

At what time of day should you take statins?

A

Night –> cholesterol synthesis occurs at night.

42
Q

Describe the Potential Toxicities of the Statins.

A
  1. Elevated serum aminotrasnferase activity –> bad in people with underlying liver conditions cause it causes Malaise, Anorexia, and Precipitated LDL
  2. Don’t use if you have liver problems

3, Increased serum CK levels, associated with exercise. (muscle weakness)

43
Q

Describe the application of CYP enzymes to statin metabolism and any drug/drug interaction that may occur.

A

Lovastatin, Simvastatin, and Atorvastatin are metabolized thru CYP3A4.

Fluvastatin and Rosuvastatin are metabolized by CYP2C9

Pravastatin is sulfonated.

44
Q

What’s the layman’s term for Niacin?

A

Vitamin B3

45
Q

Niacin increased and decreases levels of what in the blood?

A

Decreases: VLDL, LDL, and Lp(A)

Increases: HDL

46
Q

Describe the MOA of Niacin.

A

Niacin inhibits VLDL secretion, which results in decreased VLDL and LDL in the blood, as well as decreased Lp(A) because Lp(A) is an LDL derivative.

It also causes the catabolic rate for HDL to decrease, prolonging its life.

In the liver, it inhibits the intracellular lipase of adipose tissue, possibly reducing even the production of VLDLs by decreasing the free fatty acid flux.

47
Q

T/F There are other agents that will reduce the levels of Lp(A) other than Niacin.

A

FALSE! Niacin is the only thing that reduces Lp(A) levels.

48
Q

Describe the toxicity of Niacin.

A
  1. Harmless, cutaneous vasodilatation and warmth sensation at the beginning of the dosing regimen.
    - prevent with aspirin or ibuprofen
  2. Puritis, rashes, dry skin and mucous membranes.
  3. Acanthosis Nigricans (contradictory… but it happens.. and you need to stop taking niacin immediately)
    INCREASES INSULN RESISTANCE
  4. Hyperuricemia (can cause gout)
    • give Allopurinol - xanthine oxidase inhibitor that prevents the synthesis of uric acid.
49
Q

Name the Fibric Acid Derivatives

A

Gemfibrozil

Fenofibrate

50
Q

You want to give the patient the Fibrate drug with the shortest half-life. Which do you choose?

A

Gemfibrozil has a T/2 of 1.5 hours.

Fenofibrate has a T/2 of 20 hours

51
Q

How are vibrates eliminated?

A

Kidney

52
Q

MOA of Fibrates

A

Fibrates are ligands for the nuclear TF, PPAR-a, which causes transcriptional up regulation of LPL, Apo-A1 and Apo-A2 (HDL components that take cholesterol from tissues).

Causes increase in fatty acid oxidation in liver and striated muscle, and increased LPL lipolysis.

DECREASE LIPOLYSIS IN ADIPOSE CELLS. (?)

53
Q

What drug do you want to use if you’re trying to elevate HDL levels?

A

Niacin - only drug that causes significant increase (because it prevents the breakdown of it)

54
Q

Fibrates cause reductions in blood levels of what?

A

VLDL

There is only modest reduction of LDLs.

55
Q

If you’re going to use a Fibrate and a Statin combined, which vibrate do you use?

A

Fenofibrate

56
Q

Toxicity of fibrates

A

Look it up.

57
Q

What class of drug do the following drugs fall under?

Colestipol
Cholestyramine
Colesevelam

A

Bile Acid-Binding Resins

Aka “Resins”

58
Q

MOA of Resins

A

Bile acids are the metabolites of cholesterol, and are normally reabsorbed into the jejunum and ileum. Excretion of bile acids is increased 10x when Resins are given.

Increased hepatic conversion of cholesterol to bile acid via 7a-hydroxylation. (normally controlled by a negative feedback loop of bile acid buildup)

This results in increased expression of the LDL receptor, which clears the blood of 20% of its LDL at max dosage.

59
Q

Which disease can Resins not treat?

A

Homozygous familial hypercholesterolemia

the MOA involves up regulation of LDL receptor in the liver, and those with homozygous familial hypercholesterolemia don’t have any functional LDL receptor.

60
Q

What is the only disease on the charts that merited use of a Resin?

A

Heterozygous familial hypercholesterolemia.

NOTHING ELSE

61
Q

Toxicity of Resins

A

Constipation and bloating, relieved by dietary fiber.

Heartburn and diarrhea

Malabsorption of Vit K and folate

62
Q

What drug can be administered with Resins to prevent GI side effects?

A

Psyllium

63
Q

If You’re giving a resin in conjunction with another drug, what should the dose timing look like?

A

Take the resin wither 1 hour before or 2 hours after the other drug, because the increased bile secretion caused by the resin can change the pH of the intestines, throwing off the absorption of the other drug.

64
Q

What’s the inhibitor of stroll absorption? (Only one.)

A

Ezetimibe

65
Q

MOA of ezetimibe.

A

Selective inhibitor of intestinal absorption of cholesterol and phytosterols, as well as decreases reabsorption of cholesterol secreted in the bile.

Target = NPC1L1 transport protein

66
Q

Describe the Pharmacokinetics of Ezetimibe

A

Oral –> absorbed and conjugated to an active GLUCARONIDE in the intestine –> peak blood level in 12-14 hrs

80% secretion in the feces

67
Q

Ezetamibe is synergistic with _____________.

A

Statins (reductse inhibitors)

Together, they produce a 25% decrease in LDL in the body, beyond what either would do alone.

68
Q

T/F Ezetamibe is not a CYP substrate

A

TRUE

69
Q

T/F: VLDL Levels can increase with the use of a Resin.

A

TRUE: so you add niacin or another drug that decreases VLDL

70
Q

What do Omega-3’s do?

A

Activate PPAR-a, which reduces TGs

Same MOA as Fibric Acid Derivatives

CV Block (13 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions