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Hyperlipidemia > Drugs > Flashcards

Drugs Flashcards

1
Q

What are statins good at?

A

Reducing LDL

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2
Q

What are fibrates good at?

A

Reducing triglycerides

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3
Q

What is niacin good at?

A

Increasing HDL

Reducing triglycerides

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4
Q

How do statins work?

A

Inhibition of enzyme (HMG-CoA reductive) has two effects:

(1) decrease liver cholesterol synthesis => inc. LDL receptor expression => dec. LDL and VLDL
(2) decrease liver cholesterol synthesis => dec. liver VLDL production => dec. TG

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5
Q

Which statins are the best at lowering LDL?

A

Atorva, Rosuva

Simva

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6
Q

Which statin is the lowest intensity?

A

Fluva

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7
Q

What are some other statin benefits, besides lipid reduction?

A

Increased endothelial vasodilation

Inc. plaque stability

Dec. inflammation

Dec. lipoprotein oxidation

Dec. platelet aggregation + fibrinogen (less clots!)

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8
Q

Why are statins dosed at night?

A

Period with highest cholesterol synthesis

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9
Q

Which statins would be best for AM dosing?

A

Atorva and Rosuva

Have longer half-lives and will last longer to reach night-time cholesterol synthesis

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10
Q

Which statins are prodrugs that get activated in the liver?

A

Lova

Simva

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11
Q

AE’s for statins

A

Mild: headache, rash, GI upset

Liver dysfunction

Myalgia

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12
Q

Statins DDIs

A

CYP3A4 inhibitors - ex: amiodarone
(Affects lova, simva > atorva&raquo_space;> Prava, rosuva, fluva)

Fibrates

Niacin = 1+ g/day

Bile acid resins

Warfarin

Red yeast rice

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13
Q

How do fibrates work?

A

Activate receptor - PPARalpha

PPAR = peroxisome proliferator-activated receptors

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14
Q

How do fibrates work?

A

PPAR activators

(1) more ffa oxidation => less TG made in liver (less building blocks for VLDL)
(2) Inc. LPL and less apoC made => more clearance of TG-rich lipoproteins = dec. VLDL and TG
(3) More LDL receptors made => dec. VLDL and LDL
(4) Inc. apoA made => more HDL => more reverse chol. Transport

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15
Q

What are some other effects fibrates have?

A

Inc. HDL

Dec. triglycerides

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16
Q

Which fibrate is metabolized in the liver and thus contraindicated in hepatic dysfunction?

A

FENOfibrate (converted to fenofibric acid)

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17
Q

What are some adverse effects of fibrates?

A

GI (nausea, dyspepsia, abdominal pain)

Myopathy

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18
Q

What are some DDI’s with fibrates?

A

Statins => myopathy (avoid with GEMIfibrozil)

Bile acid resins => dec. bioavailability
Take fibrate 1 hour before or 4 hours after

Warfarin => inc. INR

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19
Q

When are fibrates contraindicated?

A

Severe renal or hepatic failure

Pregnancy

Children

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20
Q

What is another name for Niacin?

A

Vitamin B3

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21
Q

What sites does Niacin work at?

A

Adipose tissue

liver

Plasma

Macrophages

22
Q

What effect does niacin have in adipose tissue?

A

Inhibits adenylyl cyclase => dec. cAMP

=> dec. hormone-sensitive lipase
=> dec. TG lipolysis and FFA release

23
Q

What effects does Niacin have in the liver?

A

Dec. FFA transport => dec. TG made in liver => less VLDL => dec. TG and LDL

Dec. liver clearance of ApoA in HDL => more HDL in plasma => more reverse cholesterol transport => dec. LDL

24
Q

What effect does Niacin have in plasma?

A

Increased LPL activity => dec. TG, VLDL, chylomicron

25
Q

What effect does niacin have in macrophages?

A

Increased scavenger receptor and cholesterol exporter => dec. cholesterol in foam cells

26
Q

What are two metabolites of niacin (and their effects)?

A

Nicotinuric acid = vasodilation (flushing)

Nicotinamide = toxic metabolites for liver

27
Q

What are Niacin adverse effects?

A

Flushing, headache, itching

GI: nausea, dyspepsia, peptic ulcer

Dry skin

Acanthus nigricans (darkening of skin)

Hepatotoxicity

Hyperglycemia

Myopathy

Hyperuricemia

28
Q

What are some Niacin DDIs?

A

Statins: lower risk with niacin @ less than 1 g/day

Bile acid resins: colestipol&raquo_space;> cholestyramine
Separate by 4-6 hours!

29
Q

Niacin is the only drug that does what?

A

Lower LpA

30
Q

For which patients should Niacin be avoided?

A

Uncontrolled diabetics

Active PUD

liver disease

Gout

31
Q

What does Ezetimibe do?

A

Inhibits cholesterol absorption

32
Q

How does Ezetimibe inhibit cholesterol absorption?

A

Binds cholesterol transporter and leads to decreased dietary and biliary cholesterol uptake

Decreased cholesterol in chylomicrons and less delivered to liver

Dec. delivery to liver leads to increased production of LDL receptors (which will take up more LDL)…but then that also leads to more cholesterol made in liver from LDL uptake :(

33
Q

What effects does ezetimibe have?

A

Decreases LDL

NO EFFECT on TG or HDL

34
Q

What are some adverse effects of Ezetimibe?

A

Headache, diarrhea

Arthralgia

fatigue
Cough

Inc. serum transaminases

Hypersensitivity (rare)

35
Q

What are DDIs associated with Ezetimibe?

A

Minimal (since not absorbed!)

Bile acid resins will decrease Ezetimibe’ absorption - take 2 hrs before or 4 hours after BAR

Warfarin : may inc. levels

Cyclosporine : may inc. levels

36
Q

What’s Ezetimibe’ relationship with statins?

A

Additive to decreased LDL by additional percentage

37
Q

What are some bile acid resins (BARs)?

A

Cholestyramine

Colestipol

Colesevelam

38
Q

How do BARs work?

A

In anion exchange resins:
Bind bile acids in gut to excrete them in stool => dec. bile acid stores

In the liver:
Inc. bile acid synthesis with dec. hepatic cholesterol => more LDL receptors made => dec. LDL (from uptake)

Dec. cholesterol in liver also increases HMG-CoA reductase activity to increase chol. Synthesis => dec. LDL receptor, Inc. VLDL, Inc. TGs

39
Q

Which BAR would you recommend for a patient with GI upset?

A

Colesevelam

40
Q

What are adverse effects associated with BARs?

A

GI intolerance: bloating, dyspepsia, gas, nausea, constipation
Gritty slurry from cholestyramine and colestipol

Increased TGs (avoid in severe hypertriglyceridemia)

41
Q

What are some BAR DDIs?

A

Interfere with drug absorption so separate 1 hour before or 3-4 hours after!!!

Fluva/Pravastatin
Niacin
Fibrates
Ezetimibe

Warfarink, beta-blockers, thiazides, furosemide
Propranolol, levothyroxine
Vitamins A, D, E, K

42
Q

What effect does Fish oil have?

A

Inhibits VLDL and TG synthesis in liver

43
Q

What are adverse effects of fish oil?

A

GI upset, burping, altered taste

44
Q

What are some cons of fish oil?

A

Does not lower LDL (may actually increase it)

No effect on HDL

45
Q

How do PCSK9 inhibitors work?

A

Prevent PCSK9 from binding to LDL receptors (which would promote their degradation within the liver and result in higher LDL levels in the blood)

46
Q

What are indications for PCSK9 inhibitors?

A

Familial hypercholesterolemia

Clinical atherosclerotic CVD

Adjunct to diet and maximally tolerated statin therapy in pts who require additional LDL lowering

47
Q

What are some adverse effects associated with PCSK9 inhibitors?

A

Hypersensitivity/ injection site reactions

Increased liver function tests (Alirocumab)

Nasopharyngitis, upper respiratory infection, flu

Very low LDL

Antibody formation

48
Q

What are some Tx combos?

A

Statin + Ezetimibe

Statin + BAR

Niacin + BAR

Statin + Niacin + BAR

49
Q

Which combo lowers LDL the least?

A

Niacin + BAR

50
Q

Which combo lowers LDL the most?

A

Statin + niacin + BAR

Hyperlipidemia (2 decks)

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