Antihyperlipidemic Agents

Front 1

LDL contains high levels of ___ which readily deposits in the subendothelial space of arteries. Chylomicrons & VLDL cannot, although VLDL gives rise to ILD which can.

Back 1

Cholesterol

Front 2

high LDL increases the incidence of adverse events associated with coronary artery disease whereas ___ is antiatherogenic by removing free cholesterol generated from the metabolism of chylomicrons & VLDL.

Back 2

HDL

Front 3

“STATINS” are __________

Back 3

HMG CoA REDUCTASE INHIBITORS (HMG = 3-hydroxy-3-methylglutarate) –

Front 4

Statins inhibit the conversion of HMG CoA to _________, the rate-limiting step in the synthesis of cholesterol. Cholesterol synthesis is, therefore, decreased.

Back 4

mevalonic acid

Front 5

Statins are heavily extracted by the _____.

Back 5

liver

Front 6

Peripheral levels are very low. Therefore, their effect is predominantly on __________.

Back 6

hepatocytes

Front 7

As hepatocyte cholesterol synthesis decreases, the number of LDL receptors __________.

Back 7

increases

Front 8

WHAT IS THE CLINICAL SIGNIFICANCE OF THIS?

Back 8

collects more LDL from blood stream to meet cholesterol needs

Front 9

Macrophages can also take up LDL that contains acetylated or oxidized ____.

Back 9

apoB-100

Front 10

Excessive uptake by macrophages of modified (acetylated or oxidized) LDL transforms macrophages into ______.

Back 10

FOAM CELLS

Front 11

WHAT IS THE CLINICAL SIGNIFICANCE OF THIS?

Back 11

They are athrogenic, just like LDL

Front 12

STATINS also decrease ___ b/c they also contain apoB-100 which is recognized by LDL receptors and is internalized by hepatocytes.

Back 12

IDL

Front 13

The decrease in IDLs CONTRIBUTE TO THE decrease IN PLASMA LDL? WHY?

Back 13

Yes, cuz IDL can become LDL (is a precursor)

Front 14

Hepatic synthesis of _____ is also decreased.

Back 14

apoB-100

Front 15

WHY IS decrease of Hepatic synthesis of apoB-100 THIS IMPORTANT?

Back 15

How receptor recognizes LDL & IDL

Front 16

Cholesterol contains high levels of ___ which readily deposits in the subendothelial space of arteries. Chylomicrons & VLDL cannot, although VLDL gives rise to ILD which can.

Back 16

LDL

Front 17

high LDL increases the incidence of adverse events associated with coronary artery disease whereas ___ is antiatherogenic by removing free cholesterol generated from the metabolism of chylomicrons & VLDL.

Back 17

HDL

Front 18

“STATINS” are __________

Back 18

HMG CoA REDUCTASE INHIBITORS (HMG = 3-hydroxy-3-methylglutarate) –

Front 19

Statins inhibit the conversion of HMG CoA to _________, the rate-limiting step in the synthesis of cholesterol. Cholesterol synthesis is, therefore, decreased.

Back 19

mevalonic acid

Front 20

Statins are heavily extracted by the _____.

Back 20

liver

Front 21

Peripheral levels are very low. Therefore, their effect is predominantly on __________.

Back 21

hepatocytes

Front 22

As hepatocyte cholesterol synthesis decreases, the number of LDL receptors __________.

Back 22

decreases

Front 23

WHAT IS THE CLINICAL SIGNIFICANCE OF THIS?

Back 23

-

Front 24

Macrophages can also take up LDL that contains acetylated or oxidized ____.

Back 24

apoB-100

Front 25

Excessive uptake by macrophages of modified (acetylated or oxidized) LDL transforms macrophages into ______.

Back 25

FOAM CELLS

Front 26

WHAT IS THE CLINICAL SIGNIFICANCE OF THIS?

Back 26

-

Front 27

STATINS also decrease ___ b/c they also contain apoB-100 which is recognized by LDL receptors and is internalized by hepatocytes.

Back 27

IDL

Front 28

The decrease in IDLs CONTRIBUTE TO THE decrease IN PLASMA LDL? WHY?

Back 28

--

Front 29

Hepatic synthesis of _____ is also decreased.

Back 29

apoB-100

Front 30

WHY IS decrease of Hepatic synthesis of apoB-100 THIS IMPORTANT?

Back 30

-

Front 31

VLDL is composed mainly of _________.

Back 31

triacylglycerol

Front 32

With statins, triglyceride levels decrease _____ .

Back 32

10-30%

Front 33

With statins, HDL levels increase _____.

Back 33

5-10%

Front 34

WHY do HDL levels rise.

Back 34

HDL donates cholesterol exters to other lipoP (i.e. LDL & IDL) ; in the process of doing that it gets modified so that it is no longer a HDL. when we decrease the LDLs to donate to, less HDL is modified.

Front 35

The increase in HDL removes more free unesterified _______ from extrahepatic tissues which contributes to the decrease in plasma cholesterol.

Back 35

cholesterol

Front 36

All STATINS are therapeutically ____.

Back 36

equal

Front 37

Significant effects occur in ___ wks with maximal effects in ___ wks.

Back 37

1-2
4-6

Front 38

Recommend giving statins as a single daily dose at _____ .

Back 38

bedtime

Front 39

WHY?

Back 39

Has to do with when most cholesterol synthesis takes place – in the evening

Front 40

Statins are used for a wide variety of __________

Back 40

hypercholesterolemia

Front 41

STATINS have anti-inflammatory activity as assessed by ____________ levels which are ↑ during systemic inflammation, a part of the atherosclerotic process.

Back 41

C REACTIVE PROTEIN

Front 42

High levels of C REACTIVE PROTEIN are associated with _____ survival rates

Back 42

lower

Front 43

MECHANISM

Back 43

Statins inhibit various oxidation pathways (anti-oxidant). CRP is an end product of oxidation & inflammation. Statins have an anti-inflamatory effect reduces risk of CV dz.

Front 44

STATINS are in PREGNANCY CATEGORY X: which means:

Back 44

Documented fetal abnormalities in animals or humans or evidence of fetal risk in humans. Risk outweighs benefits.

Front 45

-ProRx
-Metabolized by cyp 3A4. avoid grapefruit juice. Macrolides ( erythromycin, clorithromicin, azythromicin, derithromycin), itroconasole( conazoles are anti fungals) increase risk of rabdomyolisis.

Back 45

LOVASTATIN (Mevacor)

Front 46

SIMVASTATIN (Zocor)

Back 46

proRx

Front 47

low protein binding results in short half life (2hrs)

Back 47

PRAVASTATIN (Pravachol)

Front 48

FLUVASTATIN (Lescol)

Back 48

-

Front 49

longest acting.

Back 49

ATORVASTATIN (Lipitor)

Front 50

atorvastatin + amlodipine =

Back 50

CADUET

Front 51

WHAT IS AMLODIPINE?

Back 51

Ca++ channel blocker (CCB), treat arrhytmia’s and HTN

Front 52

decreases LDLc 46-55%

Back 52

ROSUVASTATIN (Crestor) -

Front 53

All STATINS decrease LDL decrease 25% (rosuvastatin more). For a greater effect, higher doses of _____ or _____ are recommended.

Back 53

LOVASTATIN
SIMVASTATIN

Front 54

WHY NOT USE HIGHER DOSES OF THE OTHER RXS?

Back 54

prodrug activated in the liver where it is used

Front 55

One of the SIDE EFFECTS of Statins is an ______ in plasma transaminases > 3 times the upper limit of normal. Incidence: 1-2%.

Back 55

increase

Front 56

Significance of increase in plasma transaminases is ______ damage?

Back 56

liver

Front 57

Another SIDE EFFECTS of Statins is _________– transient increase in CK-MM. Muscle tenderness, pain, weakness.

Back 57

MYOPATHY

Front 58

_______ dysfunction increases risk of rhabdomyolysis.

Back 58

Renal

Front 59

Also with Statins there have been reports of a _____ like syndrome

Back 59

lupus

Front 60

OTHER POTENTIAL USES of these two statins is to decrease the Risk of Alzheimer’s & dementias & depression.

Back 60

(pravastatin & lovastatin but not simvastatin)

Front 61

statins can also ↓ ____ in patients w/ or w/o decreasing cholesterol.

Back 61

BP

Front 62

statins may also ↓ the risk of ____.

Back 62

glaucoma

Front 63

Risk of myopathy increases in patients on ______,______ , _______, ________, & _______. Can take together if you decrease the dose of the statin.

Back 63

cyclosporine
erythromycin
itraconazole
gemfibrozil
nicotinic acid

Front 64

lovastatin & simvastatin potentiate _______ actions through an unknown mechanism, resulting in increased prothrombin time (PT).

Back 64

coumarin's

Front 65

BILE ACID SEQUESTRANTS are used Mostly for Types ___ & ____ hyperlipidemias.

Back 65

IIa
IIb

Front 66

BILE ACID SEQUESTRANTS, have Little effect on patients ________ for type IIa. These patients do not have ___ receptors.

Back 66

homozygous
LDL

Front 67

BILE ACID SEQUESTRANTS MECHANISM:

Back 67

Not absorbed systemically, action is totally in the gut—Anion exhange resin- exchange Cl- for bile acids, not absorbed so is excreted-> increased excretion of bile acids.

Front 68

WHY IS THIS IMPORTANT?

Back 68

Bile acids contain large amount of cholesterol

Front 69

WHAT DOES THIS DO TO THE LEVELS OF HEPATOCYTE CHOLESTEROL?

Back 69

Goes down—set in motion all the events previously discussed—sucks up LDL from plasma , LDL receptors go up in liver- so liver grabs the LDL when it sees apo B100

Front 70

HOW WILL HEPATOCYTES REPLACE THE BILE ACIDS?

Back 70

Make more; needs more cholesterol from plasma, LDL receptors increase on hepatocytes-

Front 71

FROM WHERE WILL HEPATOCYTES GET CHOLESTEROL?

Back 71

-plasma

Front 72

WHAT HAPPENS TO THE # OF LDL RECEPTORS? WHY?

Back 72

-
Increase, low chol levels in hepatocytes, genes transcribe LDL receptors, so grabs apo 100 on LDL, to break down and make more bile acids.

Front 73

BILE ACID SEQUESTRANTS result in a ____ drop in LDL in 1st wk with maximal effects in ~ 2 wks. HDL rises only _____.

Back 73

10-35%
~5%

Front 74

powder to mix in H20 or juice

Back 74

CHOLESTYRAMINE (Questran)

Front 75

granules & tablets

Back 75

CHOLESTIPOL (Colestid)

Front 76

tablets

Back 76

COLESEVELAM (Welchol

Front 77

SIDE EFFECTS of BILE ACID SEQUESTRANTS

Back 77

Not absorbed. No significant systemic effects

Front 78

WHAT KIND OF SIDE EFFECTS WOULD YOU EXPECT?

Back 78

-GI ( remains in gut)—bloating, cramps, constipation

Front 79

Constipation can persist resulting in _______

Back 79

impaction

Front 80

BILE ACID SEQUESTRANTS, can bind _______ charged compounds e.g. thyroxine, digoxin, anticoagulants, thiazides, furosemide, propranolol, tetracyclines, gemfibrozil, pravastatin, fluvastatin, ASA, phenobarbital

Back 80

negatively

Front 81

BILE ACID SEQUESTRANTS can decrease Absorption of ___ soluble vitamins (A,D,E,K)

Back 81

fat

Front 82

_______ and ______ absorption are also decreased.

Back 82

Vitamin C
folic acid

Front 83

TAKE ALL OTHER RXS ___ HR BEFORE OR ___ HRS AFTER TAKING A RESIN

Back 83

ONE
4

Front 84

NICOTINIC ACID = ____

Back 84

NIACIN

Front 85

NIACIN USES are TYPES __,__,__,__ hyperlipidemias

Back 85

II, III, IV, V

Front 86

NICOTINIC ACID MECHANISM

Back 86

inhibits hormone sensitive lipase (HSL) that normally mobilizes the stored fats. Decrease mobilization of peripheral fat stores

Front 87

Inhibition of hormone sensitive lipase (HSL) decreases the delivery of FFAs to the liver which decreases the synthesis of ____ & ____. Lower levels of VLDL -> lower levels of LDL. HDL is increased (mechanism unclear).

Back 87

VLDL
TGs

Front 88

** NIACIN is the only Rx that will decrease ______

Back 88

Lp(a)

Front 89

50% of patients on niacin experience vasodilation -> intense ______ & ______ involving face & upper body.

Back 89

flushing
pruritus

Front 90

vasodialation might be accompanied by _______, due to baroreptor response to decrease in BP

Back 90

palpitations

Front 91

Taking _____ 30 minutes before or _______ 1 x/day has prevented these symptoms in some patients.

Back 91

ASA
IBUPROFEN

Front 92

Niacin can also cause _____ abnormalities --chronic high doses or sustained release preps can increase serum transaminases (AST/ALT).

Back 92

Hepatic

Front 93

Niacin can also cause an increase in plasma glucose – caution if patient is ______

Back 93

diabetic

Front 94

Niacin can also cause an increase in uric acid levels -> can increase risk of _____ attack

Back 94

gout

Front 95

Niacin is also ssociated with abdominal ________

Back 95

malignancy

Front 96

Niacin is contraindicated if pt has a Hx of ________ - can precipitate an attack.

Back 96

peptic ulcers

Front 97

When used with a STATIN, niacin can increase the risk of _______

Back 97

rhabdomyolysis

Front 98

FORMULATIONS of niacin are available ____. Higher doses of some may a require prescription.

Back 98

OTC

Front 99

This formulation is absorbed over 1-2 hrs. Given t.i.d.. High incidence of flushing, GI side effects and increase blood sugar.

Back 99

Immediate release

Front 100

This formulation is absorbed over 12+ hrs. Given 1x/day. Less flushing but increase risk of hepatotoxicity

Back 100

Sustained release

Front 101

This formulation is absorbed over 8-12 hrs. Given 1x/day. Less flushing and GI side effects w/o increase risk of hepatotoxicity.

Back 101

Extended release

Front 102

when giving niacin always get BASELINE ______, _____ , _______& ______

Back 102

LIVER FUNCTION TESTS
GLUCOSE
URIC ACID
LIPID LEVELS

Front 103

NIACIN + LOVASTATIN=

Back 103

ADVICOR

Front 104

In FIBRIC ACID DERIVATIVES the MECHANISM is to activate _________ that increases transcription of ___ & decreases transcription of apoC-III, an inhibitor of LPL.

Back 104

peroxisome proliferator-activated receptor α (PPARα)

LPL

Front 105

FIBRIC ACID DERIVATIVES ↑ LPL activity -> increase hydrolysis of ____ -> decrease in VLDL.

Back 105

TGs

Front 106

FIBRIC ACID DERIVATIVES ↑ HDL by increasing transcription of genes coding for apo ___ & ___ which are major apoproteins in HDL.

Back 106

AI
AII

Front 107

FIBRIC ACID DERIVATIVES also decrease levels of plasma _______ causing a decrease in platelet aggregation. This "might" have beneficial effects on the CV system. The mechanism for this effect is unclear.

Back 107

fibrinogen

Front 108

This FIBRIC ACID DERIVATIVE is for Types IV & V. It decreases LDL, VLDL & TGs

Back 108

FENOFIBRATE (Tricor)

Front 109

This FIBRIC ACID DERIVATIVE is Preferred for Type III (familial dysbetalipoproteinemia) in which there is a mutant apoE causing an increase in IDL which, in turn, increases TG & cholesterol.

Back 109

GEMFIBROZIL (Lopid)

Front 110

SIDE EFFECTS of FIBRIC ACID DERIVATIVEs are that a ______-______ SYNDROME can occur

Back 110

MYOSITIS-FLULIKE

Front 111

This CHOLESTEROL ABSORPTION INHIBITOR, Inhibits absorption of LDL and some TGs. CAUTION: Possible allergic reaction in the form of a rash or angioedema.

Back 111

EZETIMIBE (Zetia)

Front 112

EZETIMIBE + SIMVASTATIN =

Back 112

VYTORIN