Anti-hyperlipidemic Drugs Flashcards Preview

Pharmacology - Test #4 > Anti-hyperlipidemic Drugs > Flashcards

Flashcards in Anti-hyperlipidemic Drugs Deck (63):
1

Ways that statin treatment improves patient outcomes

Less mortality, CVD disease, stroke

2

Normal significance of cholesterol and triglycerides?

Cholesterol -- Essential to cell membranes, sterol/steroid precursor
Triglyceride -- Storage form of fuel to support high energy compound generation, in structural lipids

3

What are lipoproteins all about?

Lipoproteins transport cholesterol and triglycerides in blood. Exterior phospholipid, cholesterol, and protein. Interior triglycerides and cholesterol. Regulated by apoproteins.

4

Signiificance of Chylomicrons

Involved in transport of dietary lipids from gut to liver and adipose tissue

5

Importance of apoliprotein A-1

Structural in HDL, ligand of ABCA1 receptor
Mediates reverse cholesterol transport
Made in liver and intestine

6

Importance of apoliprotein B-100

Structural VLDL, IDL, LDL, LDL receptor ligand in liver

7

Importance of apoliprotein B-48

Structural in chylomicrons
Produced in Intestine

8

Importance of apoliprotein E

Ligand for LDL receptor
Reverse cholesterol transport with HDL
Produced in liver

9

Importance of apoliprotein CIII

Foudn in chylomicrons, VLDL, HDL>LDL
Inhibits Lipoprotein lipase and interferes with ApoB and ApoE binding to hepatic receptors

10

Lipoprotein Lipase is an important part of what conversion

Chylomicrons --> Chylo remnant
VLDL --> IDL

11

Enzyme that converts from HDL to IDL

CETP

12

Most important enzyme in the synthesis of cholesterol in the liver

HMG CoA Reductase

13

Lipoprotein disorders are detected by measuring....

serum lipid after a 10 hr fast

14

Key measurements in assessing risk of CVD

Ratio of Total Cholesterol to HDL-Cholesterol
Ratio over 4.5 is associated with risk, under 3.5 desired

15

Important details on hyperlipoproteinemia

Elevated Cholesterol/LDL Levels
Atherosclerosis -- Excess accumulation of cholesterol in vascular smooth muscle
Prematures CAD
Stroke Risk

16

Hypertriglyceridemia is associated with...

Pancreatitis
Xanthomas
CHD risk

17

Subendothelial uptake of cholesterol by mps is largely facilitated by...

Scavenger Receptos
LDLR
mLDL -- SR-A, CD36

18

Mp recetors that allow mature HDL to withdrawl cholesterol

SR-B1
ABCG1

19

Mp receptor associated with giving cholesterol to an immature HDL

ABCA1

20

Three types of drugs used primarily for high cholesterol

HMG CoA Reductase Inhibitors
Bile Acid Binding Resins
Inhibitors of Cholesterol Absorption

21

Drugs used mainl for high triglycerides

Fibrates
Niacin
Omega 3 FAs

22

Mechanism of Bile Acid Binding Resins

- Inhibit the reabsorption of bile acids from intestine by binding bile acids to form insoluble complex that is excreted in feces
- Loss upregulates LDL receptors in the Liver

23

Examples of Bile Acid Binding Resins

Cholestyramine (Queastran)
Colestipol (Colestid)

24

Important therapeutic data abotu Bile Acid Binding Resins

Treatment of hypercholesterolemia, 20% drop in 2-4 weeks
Taken before meals
Can increase HDL

25

Side effects of Bile Acid Binding Resins

Constipation and Bloating aided by high fiber diet and water

26

Major drug groups that interfere with Bile Acid Binding Resins absorption

Acetaminophen
Thiazides
Warfarin, Digoxin
Fibrates
Oral Contraceptives

27

Mechanism of Action of Ezetimbe (Zetia)

Inhibits intestinal absorption of cholesterol from dietary sources and reabsorption of cholesterol excreted in bile by inhibiting NPC1L1

28

What is NPC1L1's function?

Expressed on the apical surface of enterocytes of the SI.
It senses levels of sterol in the lumen. When there is plenty, triggers a large internal absorption via clathrin)

29

Adverse effects of Ezetimibe

Low incidence of liver/skeletal muscle damage
Usually pretty well tolerated tho

30

How to distinguish between a stain and a statin prodrug

All the statins have a mevalonic acid ring, which is open. If the ring is closed, it is a prodrug and metabolism will open it.

31

Name three non-prodrug statins

Fluvastatin
Rosuvastain (Crestor)
Atorvastatin (Lipitor)

32

Name two statin prodrugs

Lovastatin and Simvastatin

33

How do HMG-CoA Reductase inhibitors work

Competitively inhibit HMG CoA Reductase, the rate-limiting enzyme in cholesterol biosynthesis
- Also upregulates LD receptors in the liber, reducing plasma cholesterol

34

Explain the mechanism of hepatic LDL receptor upregulation

Statins help bind sterols and SCAP in the ER. The lower levels of free statins allow SREBP to be moved to the golgi, where it is cleaved by SCAP to send bHLH to the nucleus. This will upregulate LDL expression in the liver

35

Why give an HMG-CoA Reductase Inhibitor

Hypercholesterolemia
Standard practive to initiate after MI

36

Details on Dosing Statins..

- Short half-life ones are takin in evenings, because nighttime is the biggest cholesterol synthesis time.
- Take lovastatin w/ food
- Otherwise, a single dose whenever

37

Lovastatin, Simvastatin, and Atorvastatin are broken down by _________. This makes them tend to accumulate in patients taking...

CYP3A4
Macrolides, Cyclosporine, Ketoconazole, Grapefruit Juice

38

Fluvastatin and Rosuvastatin are broken down by _____. They tend to accumulate with ......

CYP2C9
Cimetidine, Metronidazole, Amiodarone

39

Adverse effects of Statins....

Rhabdomyolysis (which will cause renal dysfxn)
Hepatotoxicity

40

statin rhabdomyolysis is especially associated with coadministration wtih...

Gemfibrozil

41

Drugs that work by inhibiting ApoB Lipoprotein synthesis?

Juxtapid
Mipomersen

42

How does Juxtapid work?

Small molecule inhibitor of microsomal TG transfer protein, which stopds assembly of ApoB lipoproteins in the liver and intestine (decreasing absorption).

43

Who should you prescribe Juxtapid or Mipomersen for?

Homozygous Familial Hypercholesterolemia
High risk of liver damage, only use if desperate

44

How are Juxtapid and Mipomerson dosed?

Jux -- Oral
Mipo -- SubQ Injection

45

How does Mipomersen work?

Hybridized ApoB100 mRNA in the liver to promote its degredation

46

Name same important Fibric Acid Derivatives

Gemfibrozil, Fenofibrate
Clofibrate, Ciprofibrate, Benzafibrate

47

Fibric Acid Derivative mechanism of action

bind to PPAR-alpha and regulate gene transcription w/ retinoic acid receptor. Cause a complex set of effects, but include reduced LDL, serum TGs, and elevated HDL.

48

What are some important mecahnisms by which PPARs have their effect on blood lipids

Increased in Lipoprotein Lipase
Decreased ApoCIII synth --> lower VLDL
Increased ApoA1, AIII synthesis --> higher HDL

49

Therapeutic indications fo Fibric Acid Derivatives

Hypertriglyceridemia in which VLDL predominate
Second line for mixed hyperlipidemia

50

Side effects of Fibric Acid Derivatives

Gall Stones
Skeletal Muscle Effects (Rhabdo) -- ESPECIALYL W/ Statins

51

Importna tdrug interaction of Fibric Acid Derivatives

Potentiates the effects of Warfarin

52

What is Lovaza? Mechanism of Action?

Combo of Ethyl Esters from Omega 3 Fatty Acids
Reduced TG synthesis in liver, inhibit esterification of other FAs

53

Therapeutic indications for Lovaza

Following a Lipid Lowering Diet
Severe hypertriglyceridemia (over 500)

54

Adverse effects of Lovaza

Can increase LDL (usually OK if you combine with a statin)

55

Potential way that Omega 3 FAs may promote CV health

Very similar structure to PGI3, which is a potent inhibitor of platelet aggregation

56

In order for Niacin to influence lipids, doses must be...

1-3 g/day
Typically a supplement beyond any dietary level

57

How does Nicain decrease TG levels? (conceptually)

It reduces them, increasing lipase activity and thus increasing their clearance. It also drops levels of liver VLDL production while typically increasing HDL levels.

58

How does Niacin decrease TG levels (molecularly)?

Hits GPR 109A of adipocytes, which drops cAMP and inhibits the conversion of TGs to FFAs. Fewer FFAs will cause lower production of TGs/VLDL In the liver, and thus systemically lower LDL.

59

What is niacin doing specifically in the adipocyte (I know these questions fuckin suck)

Acts on GPR109A to inhibit TG lipolysis by hormone sensitive lipase, decreasing FA transport to the liver.

60

What is niacin doing in the liver

Inhibits FA synthesis and Esterification
Reduced clearance of apoA-1, but not CEs (inc. HDL)

61

What does niacin do to macrophages?

Increased CD36 and ABCA1 expression
Decreases CE content via HDL mediated reverse transport

62

Indications for Niacin

Effective for mixed hyperlipidemia
HyperTG w/ risk f pancreatitis
Low HDL
Usually combined with resins

63

Adverse effects of Niacin

- Marked vasodilation (flushing), itching, tingling of Upper body, Headache (too much PG, treat w/ ASA or ibu)
- Hepatotoxicity