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CPR Week 4 > 3.4.3. Hypolipidemic Drugs > Flashcards

3.4.3. Hypolipidemic Drugs Flashcards

1
Q

What are HMG-CoA reductase inhibitors also known as?

A

Statins

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2
Q

What are a few examples of statins?

A

Lovastatin, pravastatin, simvastatin, atorvastatin, rosuvastatin

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3
Q

What is the mechanism of action of statins?

A

Inhibit rate-determining step in cholesterol synthesis . This and niacin best for decreasing LDL and TG

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4
Q

What are the effects of statins on LDL, HDL, and TGs?

(TG = triglyceride)

A

LDL

↓↓↓

HDL

↑

TGs

↓

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5
Q

What are some side effects of statins?

A

Increased LFTs (liver function tests), myositis, hepatotoxicity, rhabdo

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6
Q

What are some examples of bile acid resins?

A

Cholestyramine, colestipol, colesevelam

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7
Q

How do bile acid resins work?

A

Bind bile salts in the intestine thus preventing their reabsorption (along with cholesterol) in the intestine

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8
Q

What is the effect of bile acid resins on LDL, HDL, and TGs?

A

LDL

↓↓

HDL

-

TGs

Mild Increase

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9
Q

What are some side effects of bile acid resins?

A

Bad taste, bloating, constipation, impaired absorption of fat-soluble vitamins

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10
Q

What is an example of a cholesterol absorption inhibitor?

A

Ezetimibe

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11
Q

How do cholesterol absorption inhibitors work?

A

Block absorption of cholesterol in the small intestine

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12
Q

What are the effects of cholesterol absorption inhibitors on LDL, HDL, and TGs?

A

LDL

↓↓

HDL

-

TGs

-

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13
Q

What are the side effects of cholesterol absorption inhibitors?

A

Rarely increased LFTs, GI distress

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14
Q

What are some examples of fibrates/fibric acids?

A

Gemfibrozil, fenofibrate, clofibrate

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15
Q

What is the mechanism of action of fibrates?

A

Increase synthesis of lipoprotein lipase via activation of peroxisome proliferator-activated receptor-α (PPAR-α), contraindicated with hyperlipidemia

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16
Q

What are the effects of fibrates on LDL, HDL, and TGs?

A

LDL

↓

HDL

↑

TGs

↓↓↓

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17
Q

What are the side effects of fibrates?

A

Myositis, increased LFTs, gallstones

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18
Q

What is the mechanism of action of niacin?

A

Decreases formation and secretion of VLDL resulting in less formation of LDL

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19
Q

What is the effect of Niacin on LDL, HDL, and TGs?

A

LDL

↓↓

HDL

↑↑

TGs

↓

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20
Q

What is a side effect of niacin?

A

Flushed face (can be prevented by aspirin) hepatotoxicity

21
Q

What are the risk factors for CHD?

A
  • Age: men > 45, women > 55
  • Low HDL cholesterol (<40 mg/dl)
  • Total cholesterol > 200 mg/dl
  • Blood pressure ≥ 140/90
  • Cigarettes
  • Obesity
  • Diabetes (particularly type 2) - red flag
  • A family history of premature death due to CHD - red flag
22
Q

What is the pathogenesis of CHD (Coronary Heart Disease)

A
  • Endothelial cell dysfunction
  • macrophage and LDL accumulation
  • foam cell formation (macrophage + oxidized cholesterol/LDL)
  • fatty streaks form
  • smooth muscle cell migration (involves platelet-derived growth factor and fibroblast growth factor), proliferation, and extracellular matrix deposition
  • fibrous plaque formation
  • complex atheromas form
23
Q

What is a more detailed (than before) Mechanism of Action (MoA) for statins?

A
  • competitively inhibit 3-Hydroxy-3-Methylglutaryl Coenzyme A (HMG-CoA) reductase in the liver (primary action)
    • mevalonate, a precursor to cholesterol, is normally produced in a rate-limiting step. This step is catalyzed by HMG-CoA reductase.
  • intra-hepatic cholesterol synthesis is reduced
  • LDL receptors on hepatocytes are upregulated by ~180%
  • increased clearance of lipoproteins containing Apo B and Apo E (such as VLDL, IDL, LDL)
24
Q

What are some indications for using statins?

A

most hyperlipidemias

Familial Hypercholesterolemia

Combined Hyperlipidemia

25
Q

What are some ways that statins protect the heart outside of their cholesterol effects?

A
  • they improve the ability of endothelial cells to make NO, thus dilating arterioles
  • they appear to stabilize plaques by decreasing their lipid content and making them less likely to rupture
  • they may be anti-inflammatory because they decrease CRP
  • Rosuvastatin has been found to reduce thrombotic events by 43%!
    • if given immediately post-MI, statins decrease the risk of death by half!
26
Q

Lovastatin, simvastatin, atorvastatin are all metabolized by what?

A

Lovastatin, simvastatin, atorvastatin are all metabolized by CYP 3A4

ROSUVASTATIN IS NOT METABOLIZED BY THIS

27
Q

Drugs that INDUCE CYP 3A4 → DECREASE statin activity

A

Phenytoin

Barbiturates

Rifampin, etc

28
Q

Drugs that INHIBIT CYP 3A4 → INCREASE statin activity

A

Cyclosporine

Verapamil

Ritonavir

Ketoconazole, etc

29
Q

Describe the major side effect associated with both statins and fibric-acid derivatives

A

side effects of Gemfibrozil and Fenofibrate:

  • skin rash
  • GI upset
  • myopathy (especially with gemfibrozil) → increased risk of rhabdo if combined with a statin
  • anemia
30
Q

Name two compounds that can increase HDL

A
  • Statins - these two here are the ballers of the statin game
    • Atorvastatin raises HDL by 2-6%
    • Rosuvastatin raises HDL by ~8-10%​​
  • ​Niacin (nicotinic acid) (Vitamin B3) - it’s unclear whether or not raising HDL w/niacin benefits Pts, but it does raise HDL..
31
Q

How can we try to ensure the least facial flushing with niacin?

A

the least facial flushing occurs w/intermediate-release niacin

32
Q

What do we see with slow release niacin?

A

some hepatotoxicity is seen w/slow release niacin

33
Q

What are the indications for use of niacin?

A
  • used alone for hypertriglyceridemia
  • used w/statins for heterozygous familial hypercholesterolemia
  • also useful in combination w/ atorvastatin or rosuvastatin for homozygous familial hypercholesterolemia
34
Q

What are some side effects of niacin?

A
  • flushing (due to increased PGD2, but can be reduced w/aspirin or laropiprant, a PD2 antagonist)
  • pruritus, rashes
  • hyperuricemia
  • hepatotoxicity w/slow release preps
35
Q

Which of the two fibric acid derivatives is the better choice in general?

A

Fenofibrate = better choice b/c it has fewer side effects

36
Q

What are the actions of fibrates?

A
  • acts as a ligand at PPAR-alpha receptors (involved in transcription regulation)
  • increases LPLase activity → increased VLDL catabolism seen → serum triglyceride levels are lowered
  • decreased VLDL synthesis and excretion by the liver
  • increased HDL by ~10-15% (b/c PPAR-alpha is activated, more ApoA-1 is made)
  • *** these decrease the incidence of MI and CHD by 22% ! ***
37
Q

What are the broad pharmacokinetics of fibrates?

A
  • efficiently absorbed from the GI tract
  • excreted as a glucuronide conjugate through the kidneys, so these are contraindicated in Pts w/renal failure
38
Q

Why are postmenopausal women at an increased risk of CHD?

A
  • E increases the HDL cholesterol up to 15% and decreases LDL cholesterol approximately 15%.
  • However, in postmenopausal women, E causes an increased risk of heart disease & breast cancer
39
Q

What are some common drug combinations used to treat common hyperlipidemias?

A
40
Q

How does chylomicronemia present?

A

Increased chylomicrons and VLDL

41
Q

How do we treat chylomicronemia?

A

Niacin and Fibrate

42
Q

How does Familial hypertriglyceridemia present?

A

Increase in VLDL and chylomicrons

43
Q

Treatment for Familial hypertriglyceridemia

A

Niacin and fibrate

44
Q

Presentation of Familial Combined Hyperlipoproteinemia

A

Increased VLDL and REALLY increased LDL

45
Q

Treatment fro Familial Combined Hyperlipoproteinemia

A

Niacin and Statin (or resin)

46
Q

Presentation of Familial hypercholesterolemia

A

Heterozygous presents as LDL increase but homozygous, as you might expect, presents with a HUGE LDL increase

47
Q

Treatment for familial hypercholesterolemia

A

Heterozygous form - Niacin and stain/resin

Homozygous form - Niacin and atorvastatin (or rosuvastatin) specifically

48
Q

Presentation of Lp (a) hyperlipoproteinemia

A

Increase in Lp (a)

49
Q

Treatment for Lp(a) Hyperlipoproteinemia

A

Niacin and Neomycin

CPR Week 4 (19 decks)

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