Brainscape's Knowledge GenomeTM

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


See full index

Pharmacology (Fall) > Lipid Lowering Agents > Flashcards

Lipid Lowering Agents Flashcards

1
Q

What are Lipid Carriers (Lipoproteins)?

A

Triacylglycerols and cholesterol can’t flow freely in blood at high levels
- require “carriers”

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

What are the 4 types of Lipid Carriers (Lipoproteins)?

A
  • Chylomicron
  • Very Low Density Lipoprotein (VLDL)
  • Low Density Lipoprotein (LDL)
  • High Density Lipoproteins (HDL)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are Chylomicrons?

A
  • Carrier of dietary lipids from intestine
    to liver
  • TG-rich, some Chol
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are Very Low Density Lipoprotein (VLDL)?

A
  • Carrier of lipids from liver to periphery * TG-rich, some Chol
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are Low Density Lipoprotein (LDL)?

A

“BAD chol”
* Carrier of lipids from liver to periphery * Chol-rich,someTG

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

What are High density Lipoproteins (HDL)?

A

“GOOD chol”
* Scavenge cholesterol from artery wall

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

Dietary and liver-synthesized lipids are absorbed @ _______

A

small intestine

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

_______ carry absorbed fat to adipose tissue (and ~muscle)

A

Chylomicrons

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

Lipoprotein lipases on endothelial cell surfaces liberates ________ + ______

A

free fatty acid + glycerol

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

Chylomicron remnant taken up by the ________ for processing

A

liver

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

Cholesterol is synthesized in the _____

A

liver

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

Describe the process of Cholesterol

A
  • Cholesterol is synthesized in the liver
  • Liver packages TG and cholesterol into VLDL
  • VLDL carries these lipids to tissues, especially adipose
  • Lipoprotein lipases on endothelial cell surfaces liberates free fatty acid + glycerol
  • VLDL->IDL->LDL as FA are removed
  • LDL carries cholesterol to other peripheral tissues; excess is taken up again by liver
  • HDL carries excess cholesterol scavenged from vessels and tissues back to the liver
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are 2 Lipid Disorders?

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

What is Pancreatitis?

A

Pancreatitis: Inflammation of the pancreas
* Caused by elevated plasma Triglycerides
* Primarily elevated chylomicrons, VLDL as well.

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

What is Atherosclerosis?

A

Atherosclerosis - Deposition of cholesterol in arteries
* Problem in coronary and cerebral blood flow
* Caused by elevated plasma CHOLESTEROL & TRIGLYCERIDES
* Primarily derived from low density lipoproteins (LDL’s)
- 50% of Western Society have ↑ LDL levels
- favors “abnormal deposition” to vessel walls

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

Where do emboli lodge in Atherosclerosis?

A
  • Carotid artery thrombosis
  • Coronary artery thrombosis
  • Other sites?
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are risk factors for Coronary Heart Disease?

A
  • Age
    o Male >45 years of age or female >55 years of age
  • Family history of premature CHD
    o 1st degree relative (male <55 years of age or female <65 years of age when the first CHD clinical event occurs)
  • Current cigarette smoking
  • Hypertension
    o Blood pressure ≥140/90 or use of antihypertensive medication
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What steps in exogenous or endogenous pathway could you disrupt to ↓ plasma chol?

A

Cholesterol:
* ↓ GI uptake
- ↓ dietary intake in gut
- ↓ reabsorption of bile acids in gut
- ↓ absorption of cholesterol in gut

  • ↓ endogenous cholesterol synthesis in liver
  • ↓ LDL levels
  • ↓ VLDL production by the liver
  • ↑ LDL receptors on hepatocyte surface
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What are the drugs for Hypercholesterolemia?

A
  1. Non-pharmacological approach – Dietary fiber
  2. Cholesterol synthesis inhibition - Statins
  3. Cholesterol Absorption Inhibitor – Ezetimibe
  4. Bile Acid Binding Resins –
    Cholestyramine, Colestipol
  5. Inhibiting LDL receptor degradation - Evolocumab
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Non-pharmacological approach for Hypercholesterolemia?

A

Dietary fiber

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

Cholesterol synthesis inhibition drugs for Hypercholesterolemia?

A

Statins

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

Cholesterol Absorption Inhibitor drugs for Hypercholesterolemia?

A

Ezetimibe

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

Bile Acid Binding Resins drugs for Hypercholesterolemia?

A

Cholestyramine, Colestipol

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

Inhibiting LDL receptor degradation drugs for Hypercholesterolemia?

A

Evolocumab

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

What is Dietary Fiber?

A

is dietary material that is resistant to the action of digestive enzymes (soluble and insoluble)

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

What is insoluble fiber?

A

is indigestible
* Sources: vegetables, whole grains

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

What is soluble fiber?

A

can be broken down by gut microbiome * Sources: oatmeal, oat bran, fruit

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

What does the non-pharmacological approach for dietary fiber do?

A

Soluble fiber binds chol in gut to reduce plasma chol

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

What does 100g/day oat bran diet (cereal and muffins) for 3 weeks do?

A
  • Total Cholesterol  19%
  • LDL Cholesterol  23%
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What are the Choleterol Synthesis Inhibition drugs?

A
  • Rosuvastatin, atorvastatin, simvastatin, lovastatin etc
  • Drug of 1st choice for most patients with risk for coronary heart
    disease (atherosclerosis)
  • ↓ LDL levels (modest HDL increase).
  • Also ↓ triglyceride levels.
  • In patients with coronary artery disease – decreased cardiac morbidity, mortality, reduced incidence of stroke
  • Benefits seen with initial high or normal cholesterol
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What is the mechanism of action for Statins?

A
  • Inhibit HMG-CoA Reductase, the rate limiting step of cholesterol synthesis
  • Results in compensatory increase in LDL receptors
  • Best given in evening
  • Diurnal pattern of cholesterol synthesis
32
Q

What are the adverse effects & contraindications of Statins?

A
  • Generally well-tolerated
  • Major: Myopathy
  • Major (but rare): Hepatotoxicity
  • Contraindication – pregnancy
  • First pass metabolism
  • CytochromeP450 3A4 (CYP3A4) metabolizes some statins
  • Interactions
  • Avoid CYP3A4 inhibitors (Eg. in grapefruit juice)
33
Q

What would happen to plasma [Statin] if you washed the pill down with a CYP3A4 inhibitor?

A

metabolize less therefore increase levels (we count on most of it to be graded down therefore have more in circulation & we’re not counting on more)

34
Q

What is the order of bioavailability?

A
  • Simvastatin
  • Lovastatin
  • Atorvastatin
35
Q

Where is the majority of Statin LDL-C efficacy?

A

with the Starting Dose

36
Q

Statins appear beneficial toward…

A

BOTH males & females

37
Q

LDL chol ↓seems GREATER with ________ and __________

A

Rosuvastatin

and

Atorvastatin

38
Q

What are the pleotropic effects of Statins?

A
  • May increase bone formation - possible osteogenic effect
  • May reduce fracture risk in elderly patients
  • Hypertension - may lower blood pressure?
  • Dementia - decrease risk of developing dementia
  • Renal function - may help preserve renal function
  • Asthma - trials as drug for asthma
  • Cancer – under investigation
39
Q

What is an ex of pleotropic effects of Statins?

A

Eg. Rho-family GTPases involved in immune activation, Cancer cell proliferation

40
Q

What is the Cholesterol Absorption Inhibitor: Ezetimibe?

A
  • ↓ LDL levels ~15-20% when used alone
  • No effect on triglycerides or fat-soluble vitamins
  • Compensatory ↑ in hepatic cholesterol synthesis
41
Q

What is the mechanism of action for Cholesterol Absorption Inhibitor: Ezetimibe?

A
  • Inhibits a cholesterol transport protein: NPC1L1 (Neimann-pick C1-like1)
  • ~50% ↓ in dietary and biliary cholesterol absorption at the intestinal brush border
42
Q

What are the adverse effects of Ezetimibe?

A
  • Reports of myalgia, hepatitis, rhabdomyolysis, acute
    pancreatitis
  • Causal relationship unclear
  • In combination with statins – possible greater elevation of transaminases (rel. to statins alone)
43
Q

What are the interactions with Ezetimibe?

A
  • Bile acid sequestrants interfere with Ezetimibe’s actions
44
Q

Why combine Statins + Ezetimibe?

A
  • Combination is additive at lowering cholesterol
  1. Ezetimibe ↓ cholesterol uptake in gut but get compensatory ↑ in cholesterol synthesis in liver
  2. HMG-CoA reductase inhibitors block this increased synthesis
45
Q

What are the Bile acid binding resins?

A
  • Cholestyramine, Colestipol
  • (+) charged non-digestible resins which bind to bile acids in the gut
  • ↓ LDL-Chol
  • Effective alone for mild to moderate elevated LDL-C
  • Effective with statins for highly elevated LDL-C
46
Q

What is the mechanism of action for Bile acid binding resins?

A
  • Binds bile acids in intestinal
    lumen
  • Prevents reabsorption (normally 95%)
  • Less bile acid recirculated to liver
47
Q

In the presence of Bile acid binding resins, to produce new bile acids, the liver must:

A
  • Take up cholesterol (↑LDL receptors)
  • Increased cholesterol de novo synthesis
48
Q

What are adverse effects of Bile acid binding resins?

A

Major:
* May ↑ VLDL levels – unknown mechanism

Minor
* ↓ absorption of fat-soluble vitamins (-> vit K deficiency)
* Nausea, constipation, and bloating (may be helped by fiber)
* Unpleasant taste and texture
* Absorption of drugs altered (effect can be +ve, -ve, neutral)
- Ie. Digitalis, thiazides, warfarin, aspirin, etc

49
Q

Why combine Statin + Bile acid binding resins?

A
  • Combination is additive at lowering cholesterol
  1. BABRs ↓ cholesterol uptake in gut but get compensatory ↑ in cholesterol synthesis in liver
  2. HMG-CoA reductase inhibitors block this increased synthesis
50
Q

What are add-on to Statin Therapy: Drug options to lower LDL-C?

A
  • Double statin dose
  • Ezetimibe
  • Bile acid binding agent (colestipol, cholestyramine)
  • Niacin
  • Fenofibrate
  • Gemfibrozil
51
Q

High-risk Patients Achieving LDL-C Goal in Canada

Failure to achieve:

A
  • Poor adherence to treatmet
  • High baseline LDL-C (FH patients)
  • High-cholesterol diet
  • High cholesterol absorption
  • Variable statin response
  • Inability to tolerate (higher-dose) statins
52
Q

What are the Inhibiting LDL receptor degradation drugs?

A
  • Alirocumab, Evolucumab
  • Injectable antibody to PCSK9 (Proprotein convertase subtilisin kexin type 9)
  • ↓ LDL-C
  • Newest therapy for patients that can’t meet target LDL-C with Statins
  • HIGH COST
53
Q

What is the mechanism of action for Alirocumab, Evolucumab?

A
  • Antibody travels to liver, binds PSCK9, inhibits its interaction with LDL receptor
  • This interaction normally targets LDL-receptor for degradation (instead, it targets for recycling)
54
Q

What are other drugs for cholesterol lowering?

A

Lomitapide (Juxtapid)
* Microsomal triglyceride transferase protein inhibitor

  • Reduces chylomicron and VLDL synthesis
  • For Familial Hypercholesterolemia patients with defective LDL receptors
  • Expensive!
55
Q

Which step in exogenous or endogenous pathway could you disrupt to ↓ plasma TG?

A
  • ↓ dietary intake of TGs
  • ↑ Lipoprotein lipase (LPL) activity
  • ↓ VLDL secretion from liver
56
Q

What are the drugs for Hypertriglyceridemia?

A
  1. Non-pharmacological approach – Dietary fiber, fish oil
  2. Increase lipoprotein lipase – Fibrates, gene therapy?
  3. Reduce VLDL secretion – Niacin
57
Q

What are the non-pharmacological approach for Hypertriglyceridemia?

A

Dietary fiber, fish oil

58
Q

What are the increase lipoprotein lipase drugs for Hypertriglyceridemia?

A

Fibrates, gene therapy?

59
Q

What are the reduce VLDL secretion drugs for Hypertriglyceridemia?

A

Niacin

60
Q

What is the non-pharmacological approach for Dietary Fiber?

A

Both types of fiber appear effective
* Insoluble fiber is indigestible
- Sources: vegetables, whole grains
* Soluble fiber can be broken down by gut microbiome
- Sources: oatmeal, oat bran, fruit

  • Other benefits
  • Increase bulk of stool; Good for constipation
  • Decrease colonic cancer?
61
Q

What are the problems & adverse effects of Dietary Fiber?

A
  • Need large amounts
  • Gaseous distention
  • Long term effect and safety unknown
62
Q

What is the non-pharmacological approach for Fish Oil?

A
  • Omega-3 polyunsaturated fatty acids DHA and EPA
  • Main effect: ↓ VLDL production
  • Secondary effect: ↑ VLDL clearance
  • 4g/day found to reduce TG by 20-30%
  • In some trials, LDL-C somewhat increased by DHA alone
  • May not be pro-athlerogenic b/c complex effects on LDL density, oxidation status, etc
  • REDUCE-IT Trial (EPA combo with statin): 25% decrease in major adverse CV events
  • Currently available as food/dietary supplement (not regulated, label can include health claim) or prescription (regulated)
63
Q

What is the mechanism of action for Fish Oil?

A
  • Reduces NEFA delivery to liver to be used for TG synthesis by:
  • ↓ lipolytic release of FA from adipocytes (result of suppressing inflammation?)
  • ↑ NEFA uptake and B-oxidation in other tissues incl. heart and skeletal muscle
  • Several other complex cellular bioactivities likely contributes to TG lowering and other beneficial effects
64
Q

What are the problems & adverse effects of Fish Oil?

A
  • Gastrointenstinal complaints, nausea, “fish burps”
65
Q

What is the Increase Lipoprotein Lipase: Fibrates?

A
  • Fenofibrate, Gemfibrozil
  • Fibric acid derivatives
  • Activator of the nuclear receptor PPARα (peroxisome proliferator activated receptor-α)
  • Primary effect: ↓ triglycerides
  • Secondary effects: May ↑ HDL, ↓ LDL
  • Men with Coronary heart disease- after 5 yrs
  • Incidence of death was decreased even though LDL levels were unaltered
66
Q

What is the mechanism of action for Fibrates?

A
  • Activation of PPARα results in increased expression of LPL
  • Get ↑ LPL activity at various tissues (adipose, muscle)
  • Increases chylomicron and VLDL clearance from circulation

LESS TG left in chylomicron remnant & LESS TG left in VLDL remnant

67
Q

What are the adverse effects of Fibrates?

A
  • Major
  • Flu-like – muscle cramps, tenderness, stiffness, weakness
  • Increased risk of myopathy when combined with statins
  • Not as common
  • Avoid in case of hepatic or renal dysfunction
  • May potentate oral anticoagulants and hypoglycemic
    agents (↓ metabolism)
  • Use with cation with increased risk of biliary tract disease
    (ie. women, obese patients, First Nations)
  • Commonly reported in large studies
  • Non-cardiac death, incl accidents, suicide, violence etc
    – Later studies – no correlation with lipid lowering
68
Q

What is the Increase Lipoprotein Lipase: Gene therapy?

A

Alipogene Tipatvovec (Glybera)
* AAV1 delivery of LPL to patients with rare genetic LPL deficiency
* Expensive - $1.2M/yr to treat!

69
Q

What is the Reduce Hepatic VLDL Secretion: Niacin?

A
  • Water-soluble vitamin (B3) nicotinic acid aka Niacin
  • NOT nicotinamide
  • Low dose: ↑ HDL
  • Higher dose: ↓ triglycerides
  • May also ↓ LDL
  • Men with previous myocardial infarction
  • Reduced incidence of non-fatal myocardial re-infarction
  • Decreased mortality rate at 9 years
70
Q

What is the mechanism of action for Niacin?

A
  • Activates niacin receptors on adipocytes to decrease TG hydrolysis
  • Less NEFA released into circulation
    ∴ Less NEFA taken up by liver
    ∴ Less NEFA converted to TG
    and secreted as VLDL
71
Q

What are the adverse effects for Niacin?

A
  • Most serious are:
  •  liver enzymes in blood (evidence of hepatoxicity?)
  • Hyperglycemia due to insulin resistance
    – Use with caution in diabetes
  • Short term:
  • Acute skin flushing and pruritus (1-2 weeks?)
    – Blunted by asprin
  • Use with caution
  • Exacerbation of peptic ulcer ∴ avoid if at risk
  • Minor:
  • Dry eyes, blurred vision, fatigue, GI distress
72
Q

Which carries mainly TG from the liver to peripheral tissues?

A

VLDL

73
Q

Which carries mainly cholesterol to peripheral tissues?

A

LDL

74
Q

Which carries dietary lipids from the intestine to the liver?

A

Chylomicrons

75
Q

Which acts as a cholesterol “scavenger”? What does this mean?

A

HDL - brings it back to liver

76
Q

High levels of which puts you most at risk for arteriosclerosis?

A

LDL - why it’s the most targeted

Pharmacology (Fall) (28 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions