3/4 Ios Test #3 Kuma

Front 1

risk factors for dyslipidemia

Back 1

High blood cholesterol Hypertension
Smoking
Obesity
Sedentary life style

Front 2

what is the progression rate of high cholesterol?

Back 2

slow

Front 3

Benefits of lowering blood cholesterol

Back 3

1 % decrease in cholesterol = a 2% lower risk of CHD

Front 4

relationship bewtween 1st mi and blood cholesterol

Back 4

is linear

females seem to be more sensitive to increased levels of cholesterol

Front 5

Therapeutic Approaches for high TG

Back 5

Early Identification


Slow Progression

Decrease Risk Factors

Appropriate Drug Therapies
↓ Cholesterol
↓ Triglycerides

Prophylaxis ?? (statins were thought to be safe and there were thoughts to administer them to people without high TG)

slow progression through disease decreasing risk factors and appropriate drug therapies (for instance: increase in physical activity to decrease obesity)

Front 6

what is the aim of therapies for High TG?

Back 6

decrease total cholesterol
and decrease TG

Front 7

total body cholesterol reflects

Back 7

Dietary intake – 1 gm per day, 30 to 50% of which is absorbed

Endogenous synthesis – 0.6 to 1.0 gm/day.

Of the total (1 + 2) 0.7 to 1.3 gms is secreted into the bile; 50% is reabsorbed

Total body cholesterol = 125 gms (most in cellular membranes)

De novo synthesis by the liver is the major source of cholesterol

Front 8

how much dietery cholesterol is absorbed daily?

Back 8

300-500 mg

Front 9

how much cholesterol is synthesized for the liver daily?

Back 9

600mg to 1 g daily

it is very variable

Front 10

important points for cholesterol balance and metabolism

Back 10

Cholesterol synthesized by the liver, and derived from the diet, contribute to the total body burden of cholesterol.

2. Hepatic cholesterol synthesis is highly variable in response to physiologic factors, genetics and diet

Front 11

fates of dietary and endogenous cholesterol

Back 11

750 mg to 1.3g is secreted into the bile and about 50% of this is recovered in the small intestine (enterhepatic cycling) the rest is eliminated in the feces

Front 12

Total body cholesterol

Back 12

cholesterol approximates 125 gm (90% of which is localized in cellular membranes)

Front 13

what is the main source of cholesterol?

Back 13

the liver

Front 14

what happens if dietary cholesterol is eliminated

Back 14

the liver will make more

Front 15

Where does cholesterol biosynthesis occur

Back 15

liver and adrenal gland

Front 16

what is the rate limiting step in the synthesis of cholesterol

Back 16

HMG CoA reductase
it is a 2 step process

Front 17

What causes dephosphylation of HMG CoA and how does it effect activity?

Back 17

increased by insulin (dephosphorylation)

this is the most active form

Front 18

What causes phosphylation of HMG CoA and how does it effect activity?

Back 18

by glucagon (phosporylation)

inactive form

Front 19

what is HMG CoA reductase regulated by

Back 19

Allosteric by mevalonate

by insulin (dephosphorylation)
by glucagon (phosporylation)

Front 20

important points for cholesterol biosynthesis

Back 20

1. The liver is the primary site of cholesterol synthesis.

2. HMG-CoA reductase catalyzes the rate limiting
step in this biosynthetic pathway and is an ideal therapeutic
target for inhibition.

3. This enzyme is highly regulated in response to physiologic, genetic
and dietary factors.

Front 21

is the rate limitng step reversible?

Back 21

no

Front 22

cholesterol and TG transport

Back 22

cellular concentrations of cholesterol are in dynamic equalibrium with the transport form encased in lipoprotein coats.

Front 23

apoprotein component

Back 23

The apoprotein components play important roles as enzymes or ligands for specific receptors

Front 24

more protein in the lipoprotein means

Back 24

that the lipoprotein will be more dense

Front 25

chylomicrons composition

Back 25

rich in TG and cholesterol they are the largest in size

Front 26

VLDL composition

Back 26

TG and protien and cholesterol next largest in size after chylomicrons

Front 27

LDL composition

Back 27

high levels of cholesterol and TG smaller than VLDL

Front 28

HDL composition

Back 28

high concentrations of protein and a little bit of cholesterol them smallest out of all of the lipoproteins

Front 29

ligands

Back 29

peripherial protiens

Front 30

all lipoprotiens contain

Back 30

structural proteins and ligands in order to interact with receptors

Front 31

is the composition of a chylomicron dynamic

Back 31

yes it changes as it goes through circulation

FFA are continually removed from the chylomicron and taken up by the liver

Front 32

Exogenous – dietary origin of cholesterol

Back 32

dietary lipids--> small intestine-->emulsified into cylimicrons (source and fate)--> APO CII and other proteins-->circulataion

as the cylomicrons go through the capillary walls they release FFA in response to endothelial lipoprotein lipases (Apo CII)

Front 33

Apo CII

Back 33

Apo CII- activator of capillary lipoprotein lipase

Front 34

Apo A

Back 34

Apo A - structural protein

Front 35

Apo B

Back 35

Apo B-100 - required for secretion of VLDL, ligand for LDL receptor

Front 36

Apo E

Back 36

Apo E – 48 - structural protein/ligand

Front 37

Exogenous – dietary origin of cholesterol

Back 37

dietary lipids--> small intestine--> chylomicrons--> Apo CII and other proteins--> chylomicrons release FFA through actions of capillary endothelial lipoprotein lipase--> lipoprotein remnants are removed by the liver

Front 38

Apo E

Back 38

Apo E – 48 - structural protein/ligand

Front 39

Apo B

Back 39

Apo B-100 - required for secretion of VLDL, ligand
for LDL receptor

Front 40

Apo CII

Back 40

Apo CII- activator of capillary lipoprotein lipase

Front 41

Apo A

Back 41

Apo A - structural protein

Front 42

what is a source of chylomicrons

Back 42

endothial cells

Front 43

Endogenous Pathway
cholesterol transport

Back 43

Lipoproteins are synthesized by the liver

VLDL (A-100, ACII, and Apo E)--> lipoprotein lipase release FFA --> IDL-->IDL--lipoportein lipases release more FFA-->LDL--> 50% goes to the liver and 50% to peripherial tissue

Front 44

IDL

Back 44

is an intermediate lipoprotein that the liver recovers and it is re-packaged into VLDL

most IDL bind hepatic receptors (Apo E)

Front 45

LDL receptor is mediated by

Back 45

endocytosis
Apo B-100 is the ligand

Front 46

increase in LDL concentrations in the blood cause

Back 46

an increase in the LDL delivered to peripherial tissue

Front 47

circulating LDL is removed by...

Back 47

the liver the components are taken up and re-packaged

Front 48

LDL is predictive of

Back 48

CHD

Front 49

HDL is protective from

Back 49

CHD

Front 50

HDL has what flow

Back 50

unidirectional
LDL is picked up from peripherial tissue and carried back the liver with in the HDL

Front 51

proteins in the HDL act as

Back 51

enzymes
LCAT--> esterfies the cholesterol and stores it as IDL and transports it to the liver

Front 52

LCAT

Back 52

Lecithen-cholesterol acyltransferase facilitates esterfication and transfer of cholesterol

Front 53

Once free cholesterol is released in the cell, the following responses occur:

Back 53

Decreased HMG-CoA reductase activity (if sufficent amounts of cholesterol)

Activation of acyl CoA cholesterol transferase for synthesis/storage of cholesterol esters (increase in the enzymes that re-esterfy cholesterol)

Decreased mRNA for LDL receptors (

Decreased expression of LDL receptors (at the protein level)

Front 54

important points cholesterol transport

Back 54

LDL transports cholesterol from the liver to extrahepatic tissues. (unidirectional)

HDL transports cholesterol from extrahepatic tissues to the liver.(unidirectioal)

The cellular uptake of these lipoproteins occurs via receptors.

Therapeutic approaches for treating hypercholesteremia alter the secretion of certain lipoproteins and the expression of cellular receptors. (statins cause levels of LDL receptors to change)

Front 55

What are Potential Therapeutic targets for the Regulation of Cholesterol and Triglyceride Levels?

Back 55

decrease in cholesterol and TG by lifestyle modifications, medications to stop absorption, blok fat absorption

Front 56

Atherosclerosis

Back 56

Atherosclerosis and its complications represent the leading cause of mortality and morbidity in Western Society. Estimates are that approximately 41% of non-accidental deaths are a result of atherosclerosis.

Front 57

Predisposing Factors for Development and
Progression of Atherosclerosis

Back 57

Family history
Elevated LDL
Hypertension
Cigarette smoking
Diabetes mellitus Infectious microorganisms
(Chlamyd. pneumon., herpesviruses)

Front 58

Atherosclerosis definition

Back 58

A thickening (narrowing of lumen) in large to medium sized arteries of the heart and brain. The thickening is a result of an accumulation of:

Lipids
Macrophage
T-cells
Smooth muscle cells
Extracellular matrix
Calcium Necrotic debris

Front 59

where do the thickening and plaque (atherosclerosis)

Back 59

The thickening or plaque formation occurs at predictable arterial locations:

Bifurcations, branches or curvatures involving changes in blood turbulence or shear forces

Front 60

Factors Causing Endothelial Injury

Back 60

Mechanical forces of blood flow –
Changes in shear force results in increase expression of adhesion molecule genes including selectins, integrins, platelet-endothelial
cell adhesion molecules

Associated changes in permeability-
increase As a result of elevated angiotensin II
decrease Endothelial nitric oxide production
increase Certain lipids such as triglycerides

Front 61

what are the initial lesions of atherosclerosis caused from

Back 61

These initial lesions are thought to result from endothelial alterations or injury that may or may not progress

Front 62

Fatty Streak Formation

Back 62

This is an event that begins very
Early (12-14 yrs of age). Fatty streak formation results from the following:

Monocytes and T-cells accumulate
In the subendothelial space

Cellular interactions result in
activation and release of pro-
Inflammatory cytokines

Inflammation and LDL oxidation
Initiate oxidized LDL uptake by
monocytes resulting in foam cell formation.

Activated monocytes and foam cells
release cytokines initiating smooth muscle proliferation and migration.

Front 63

advanced lesions

Back 63

The progression of fatty streaks initiates responses to isolate the lesion.

Migration and proliferation of
Smooth muscle cells form a
fibrous cap over foam cells and the necrotic core consisting of cell debris, lipid and fibrous tissue

The lesions expand at the margins due to the chronic inflammation.

Front 64

unstable lesions

Back 64

Chronic inflammation is associated with continued influx of monocytes
and T-cells.

Activated monocytes, T-cells and
macrophage release enzymes
metalloproteinases, collagenases and other proteinases that initiate
destabilization of the plaque.

The cap thins and may rupture. The
marginal areas are the thinnest and least stable.

Front 65

thrombus formation

Back 65

Thinning occurs at margins
where cap formation is not
extensive.
Hemorrhage occurs from lumen or from microvessels into lumen

Front 66

Thrombus formation is facilitated
by hypercoagulatory factors:

Back 66

increase in platelet activity
increase in tissue factor (released from foam cells)
resulting in a small thrombus (unnoticed or unstable angina) or a large thrombus (ischemia or MI)

Front 67

Summary of Major Athrogenic Events

Back 67

The oxidation of LDL
Is a critical event in initiation of
The lesion

Oxidized LDL stimulates
monocyte chemotaxis

Monocytes differentiate
Into macrophage which intern-
lize oxidized LDL forming foam
cells.

The foam cells contribute to plaque formation by:
- plaque accumulation in the subendothelial space
- an ulcerated, ruptured
plaque/lesion protruding into lumen.

Front 68

where does plaque accumulation start

Back 68

in the subendothelial space

Front 69

oxidized LDL causes

Back 69

monocytes to become activated to macrophages and engulf the oxidized LDL forming foam cells

Front 70

activated macrophages cause

Back 70

and increase in cell permability allowing more LDL to cross the membrance

Front 71

macrophages + oxidized LDL=

Back 71

foam cell

Front 72

important points of arthrosclerosis

Back 72

Arthrosclerosis is a progressive inflammatory disease.

excessive LDL and chronic inflammation
LDL is a central factor involved in initiation and
progression of atherosclerosis.

Front 73

therapuetic targets to prevent arthroscerosis

Back 73

decrease circulating LDL
decrease inflammatory events that occur in the subendothelial layer

Front 74

Bile Acid Sequestrates

Back 74

Bile acids are metabolic products of cholesterol essential for dietary fat emulsification and digestion.

The rate of bile acid synthesis is proportional to the rate of bile acid removal. Thus a faster rate of bile acid removal “drives”
the rate of cholesterol conversion to the bile acids.

97% of the bile acids (daily pool 2-3 gms) are recovered by enterohepatic circulation.

Bile acid sequestrants trap bile acids thus interrupting their enterohepatic circulation which stimulates the conversion of cholesterol to bile acids.

trap bile acids irreversibly so more cholesterol is converted to bile acids thus depleting the body stores of cholesterol

Bile acid sequestrants are
anion exchange resins
(exchange bile acids for Cl -)

These agents are not absorbed or digested.

Front 75

examples of bile acic sequestrates

Back 75

Cholestyramine (Questran)
Colestipol (Colestid )
Colesevelam (WelChol)

Front 76

bile is exchanged for what

Back 76

Cl on the bile acid sepuestrate (remember it is an ion complex)

Front 77

The physiologic responses to bile acid sequestrants are complex

Back 77

Increased rate of conversion of cholesterol to bile acids

Increase in number of LDL receptors and increased hepatic uptake of LDL (because depleting body of cholesterol and the liver can bind circulating LDL more efficiently so there is a decreae in LDL)

Increased rate of cholesterol biosynthesis (increase HMG CoA reductase) homeostatic response

Increased rate of bile acid production and increased uptake of LDL
will eventually offset increased production of cholesterol

Overall net result is 20 -25% reduction in LDL cholesterol

Front 78

adverse effects of Bile Acid Sequestrates

Back 78

no systemic toxicities because they are not absorbed.
The most common side effects are bloating and constipation. It is recommended that patients increase dietary fiber. The potential of decreased absorption of fat soluble vitamins is a consideration

Front 79

Drug interations with bile acid sequestrates

Back 79

The ability of these resins to bind negatively charged
drugs is predictable:
thyroxin, digitalis, glycosides, anticoagulants, propranolol,
tetracycline, furosemide, gemfibrozil, pravastatin,
fluvastatin.

fluvastatin.
The interactions can be avoided by taking the drugs 1 hour before or 4 hours after the resin.

Front 80

The Statins: HMG-CoA Reductase Inhibitors

Back 80

These agents represent a significant advancement in treating
hypercholesteremia. Originally isolated from Penicillium, Asper-
gillus and Monascus.

Selective mechanism of action
Potent
Few side effects

Front 81

MOA of statins

Back 81

Mechanism of action - the statins are competitive inhibitors of HMG CoA reductase (Ki = 1 nM)

Front 82

statins inhibit....

Back 82

HMG Co A reductase preventing the formation of mevlanate

Front 83

is the reaction speed of statins

Back 83

Rapid formation of EI complex with dissociation Ki = 1 nM

Forward rate (Kf = 0.019 s-1) to form a tightly bound EI*

Slower reverse rate (Kr = 0.009 s-1)

Overall steady-state inhibition constant of Ki* = 0.1 nM

Front 84

Other Beneficial Action of the Statins

Back 84

Endothelial cell function is improved through the statins ability to increase coronary
vasodilatation in response to acetylcholine. The mechanism of action is by stabilization of NO synthase mRNA

Plaque stability is enhanced by inhibition of smooth muscle proliferation.

Decreased inflammation is documented possibly through modulation of inflammatory cytokine release/actions.

Decreased LDL oxidation is partially mediated by the statins

Platelet aggregation is reduced by the statins.

Front 85

Statins

Back 85

Lovastatin (Mevacor )

Simvastatin (Zocar )

Pravastatin (Pravachol )

Fluvastatin (Lescol )

Atorvastatin (Lipitor )

Rosuvastatin (Crestor )

Front 86

Important Features of statins

Back 86

The beta-hydroxy derivative is
the active form

Lovastatin and simvastain are prodrugs

Pravastatin and Atorvastatin
are administered as the Na+
and Ca++ salts respectively

MOA:
decrease cholesterol synthesis
decrease hepatic cholesterol pool
increase LDL receptor number

Front 87

absorption and excretion of statins

Back 87

Diversity in the absorption and excretion of the various statins are prominent. The important points to note are the high degrees of plasma protein binding and the differences in half-lives (Atorvastatin and Rosuvastatin upwards to 20 hrs)

The therapeutic use is for treating hypercholesteremia. The general response 20 to 80 mg/day is a 25% decrease in total cholesterol and 30-35% decrease in LDL cholestrtol. HDL levels may increase up to 10%. These agents can be admin-
istered with resins, fibrates or nicotinic acid

HDL effects are not consistant across statins

Front 88

adverse effects of statins

Back 88

Adverse Effects: Generally considered very safe

GI disturbance (10% frequency)

Liver dysfunction ( less than 1%) manifested in increased ALT and AST. Liver function tests are preformed before and 2 to 3 times during the first 6 months of therapy.

Myotoxicity (muscle wasting) evidenced in elevated CPK. This is less rare than the liver dysfunction.

Hepatotoxicity and myotoxicity are observed more often in
patients taking other drugs metabolized by certain P-450
systems

Front 89

CPK

Back 89

creatine phospho kinase

Front 90

drugs that Inhibits CYP450 3A4 and their effects on statins

Back 90

increase serum drug concentration

Clarithromycin, erythromycin, troleandomycin, cyclosporine, fluconazole, itraconazole, ketoconazole, grapefruit juice, verapamil

Front 91

drugs that Induces CYP450 3A4 and their effects on statins

Back 91

decrease serum concentrations of statins

Barbiturates, carbazepine, griseofluvin, nafcillin, phenytoin, primidone,rifabutin, rifampin, troglitazone

Front 92

drugs that Inhibits CYP450 2C9 and their effects on statins

Back 92

increase serum fluvastatin or rosuvastatin concentrations

Cimetidine, trimethoprim-sulfamethoxazole, fluoxetin, isoniazid, itraconazole, ketokonazole

Front 93

drugs that Induces CYP450 2C9 and their effects on statins

Back 93

decrease serum fluvastatin or rosuvastatin concentrations

Barbituates, carbamazepine, phenytoin, primidone and rifampin

Front 94

grapefruit juce and statins

Back 94

P4503A inhibition --> in small intestine so the AUC increase

Esterase inhibition--> those drugs that are prodrugs concentrations of the active drug would be decreased.

Front 95

Inhibitors of Cholesterol Absorption

Back 95

Ezetimibe (ZETIA®) is an azetidinone originally evaluated as an ACAT (Acyl coenzyme A: cholesterol transferase) inhibitor but was found to efficiently inhibit cholesterol absorption.

This agent is well absorbed following oral administration and undergoes glucuronidation in the intestine to yield the active metabolite. The metabolites undergo extensive intrahhepatic circulation which accounts for the prolonged t1/2 of 22 hrs. Elimination is by fecal route

The side effects are few

Very effective when used in combination with statins (ezetimibe + simvastatin; VYTORIN®)

Front 96

why does ezetimbe have a half life of 22 hours

Back 96

enterohepatic cycling

Front 97

what source of cholesterol does ezetimbe block

Back 97

dietary

Front 98

is ezetimbe a prodrug

Back 98

yes

Front 99

why are the SE of ezetimbe few

Back 99

because it only targets the enterocytes in the small intestine

(epithelial cells that line the small intestine, they have receptor sites for dietary cholesterol

Front 100

metabolism of ezetimbe

Back 100

This agent is well absorbed following oral administration and undergoes glucuronidation in the intestine to yield the active metabolite. The metabolites undergo extensive intrahhepatic circulation which accounts for the prolonged t1/2 of 22 hrs. Elimination is by fecal route.

Front 101

Statins /Vytorin and Myopathy

Back 101

10 % of patients complain of muscle pain
is caused from the inhibition of HMG CoA reductase

Front 102

Effects of CoQ10 Supplementation on Plasma CoQ10 Levels

Back 102

muscle pain is decreased (44% less muscle pain in the treatment group

Front 103

Co enzyme Q10

Back 103

is a product of catabolic metabolism that is dependent/involved in the HMG Co reductase pathway

involved in the electron transport chain at a micochondrail level

without adequerte stores of Q10 electron transport is disrupted and need adequate levels of HMG CoA

Front 104

melvalonate results in restoration of....

Back 104

Co enzyme Q10

Front 105

Nicotinic Acid

Back 105

It was first reported in 1955 that this
B-complex vitamin reduced triglyc-
erides and cholesterol.

This agent does not directly reduce cholesterol. It is used to lower VLDL
and LDL levels.

The mechanisms by which this agent works are poorly understood:

1. Inhibits mobilization of free fatty acids from liver and peripheral tissues
2. Decreases hepatic synthesis and secretion of hepatic VLDL
3. Decreased VLDL production results in decreased LDL levels
4. The overall result is a significant (upwards to 80% decrease in tirglycerides and upwards to a 15% reduction in LDL. HDL may increase
30%
5. The effects of niacin are amplified when administered in combination
bile acid sequestrants

Front 106

does nicotinic acid reduce LDL

Back 106

no

Front 107

does nicotinic acid reduce TG

Back 107

yes

Front 108

does nicotinic acid increase HDL

Back 108

yes

Front 109

nicotinic acid administration and SE

Back 109

Administered in high doses ( 2 to 6 gms/day divided at each meal.) Rapidly absorbed displaying a half-life of 1 hour.

The side effects are numerous and can be serious:

Abnormal hepatic function manifested in elevated liver function tests (jaundice and elevated ALT/AST)

Intense flushing and pruritis - this tends to decrease with use

Decreased glucose tolerance

Rare effects include cardiac arrhythmias and palpitations

Should not be administered to pregnant women

Front 110

fibirc acids

Back 110

Chlofibrate is the prototypical
Fibric acid.

Clofibrate (Atromid-S  )

Gemfibrozil (Lopid )

Fenofibrae (Tricor  ) – newest
agent in this class

Note that all these agents resemble,
In part, short-chain fatty acids.

The acids are the active forms of these drugs (pKa=3.5). Ester hydrolysis of Atromid and Tricor yield active drug

Front 111

fibric acids that are prodrugs

Back 111

fenofibrate
clofibrate

Front 112

fibric acids are first line treatment for what patients

Back 112

those with high TG

Front 113

MOA of fibric acids

Back 113

Mechanisms of Action: There numerous and complex mechanisms of action that can be summarized as follows:

Stimulation of fatty acid oxidation in liver and muscle via interactions with the Peroxisome Proliferator-Activated Receptors (PPAR).

2. Stimulate lipoprotein lipase activity through interactions with CII & CIII resulting in mobilization of free fatty acids from liver and peripheral tissues

Increase efficiency of hepatic uptake of lipoproteins

Decreased hepatic synthesis and increased oxidation of fatty acids

The cumulative result is decreased VLDL production with slight decrease in cholesterol. Thus, these agents are useful in lowering triglyceride levels.

Front 114

fibric acids andPeroxisome Proliferator-Activated Receptors (PPARS)

Back 114

PPARS are a family of nuclear receptors or transcription factors, some of which play major roles in lipid and carbohydrate metabolism. The subtypes of most importance to our interests are PPAR and to a lesser extent PPAR. These proteins function as soluble receptors which bind ligands such as fatty acids, prostaglandins or certain drugs like the fibric acids.

cause and increase in enzymes that increase fatty acid oxidation and decrease fatty acid synthesis

Front 115

fibric acid absorption and excretion

Back 115

Absorption and excretion - all are well absorbed, display a
high degree of protein binding and undergo enterohepatic
circulation. The half-lives range from 1-5 hours

Front 116

SE of fibric acids

Back 116

GI discomfort
Transient elevations in ALT/AST values
Flu-like symptoms when used in combination with statins
Can produce cholelithiasis (Clofibrate) (gallstones)
Can enhance the actions of warfarin (competitive protein binding)
Not for use in patients with hepatic or renal dysfunction
Not for use in children or pregnant women

Front 117

what is the livers response to low LDL (chronically)

Back 117

Increase of LDL receptors (cellular response) to harvest LDL cholesterol (indirect action)

Front 118

why is it important to check vitamin D levels in regards to dyslipidemia?

Back 118

Hypothyroidism and low vitamin D levels increase the risk of statinassociated
myalgia and myopathy; measure thyroid function (TSH) and
vitamin D in patients with myalgia while on statin therapy

vitamin D supplements may help get rid of the muscle pain

Front 119

management of myalgia in regards to statins

Back 119

Concurrent use of CoQ-10
- Alternate day dosing of long half life statins (e.g., atorvastatin,
rosuvastatin)
- Using an NSAID or other analgesic should not be recommended

Front 120

can paitents with myalgia be on a statin

Back 120

yes

Front 121

can patients the have myopathy be on a statin

Back 121

no

Front 122

Monitoring for statins

Front 123

are statins ok with a fibrate?

Back 123

↑ myopathy risk if given in combination with a fibrate (especially
gemfibrozil) and possibly niacin

Front 124

what cyp enzyme are lovastatin and simvastatin metabolized by?

Back 124

CYP3A4

Front 125

what combinations should be avoided with lovastatin and simvastatin?

Back 125

Simvastatin and lovastatin are metabolized by the CYP3A4:

Front 126

weaker inhibitors of CYP3A4 and dose limitations

Back 126

Weaker inhibitors have specific dose limitations with certain statins:
− Amiodarone or verapamil: Max dose of simvastatin is 20 mg/daily
and lovastatin is 40 mg/day
− Cyclosporine: Max dose of simvastatin is 10 mg/day, lovastatin is
10 mg/day, and rosuvastatin is 5 mg/day
− Gemfibrozil: Max dose of simvastatin is 10 mg/day lovastatin is 20
mg/day and rosuvastatin is 10 mg/day (can use a different statin or a different fibrate)

Front 127

contraindications of statins

Back 127

Contraindications: Pregnancy, active liver disease

Front 128

comments on statins

Front 129

stellar study

Front 130

rank of statin potency

Back 130

fluva<prava<lova<simva<atorva<rosuva

Front 131

doubling the dose of a statin produces and additional ___% decrease in LDL from baseline or an additional ___ mg/dL LDL drop

Back 131

6%
10 mg/dL

Front 132

atorvastatin starting dose and usual dosing range

Back 132

starting: 10,20,40
range: 10-80

Front 133

Fluvastatin starting dose and usual dosing range

Back 133

starting: 20,40
range: 20-40

Front 134

slow release fluvastatin starting dose and usual dosing range

Back 134

starting: 80
range: 80

Front 135

lovastatin starting dose and usual dosing range

Back 135

starting: 20
range: 10-80

Front 136

ext-release lovastatin starting dose and usual dosing range

Back 136

starting: 20,40,60
range: 10-60

Front 137

pravastatin starting dose and usual dosing range

Back 137

starting: 40
range: 10-80

Front 138

rosuvastatin starting dose and usual dosing range

Back 138

starting: 10, 20
range: 5-40

Front 139

simvastatin starting dose and usual dosing range

Back 139

starting: 20,40
range: 5-80

Front 140

do you have to start with the lowest dose when starting a statin?

Back 140

no start with the approved starting doses that will produce the desired LDL reduction

Front 141

When lipid-lowering drug therapy is used in any moderately high,
high, or very high risk patient intensity should be sufficient to attain a ____ %LDL-C reduction

Back 141

30-40%

Front 142

atrovastatin dose per day and LDL reduction percentage

Back 142

dose: 10
39%

Front 143

lovastatin dose per day and LDL reduction percentage

Back 143

dose: 40
31%

Front 144

pravastatin dose per day and LDL reduction percentage

Back 144

dose: 40
34%

Front 145

simvastatin dose per day and LDL reduction percentage

Back 145

dose: 20-40
35-41%

Front 146

Fluvastatin dose per day and LDL reduction percentage

Back 146

dose: 80
35%

Front 147

rosuvastatin dose per day and LDL reduction percentage

Back 147

dose: 5-10
39-45%

Front 148

when should lovastatin, simvastatin and fluvastatin be taken?

Back 148

Lovastatin, simvastatin and fluvastatin must be dosed in the
evening to maximize effect:
- Diurnal rhythm of cholesterol production with maximum
cholesterol production nocturnally
- Long half life statins (atorvastatin, rosuvastatin) and pravastatin
can be dosed any time of the day

Front 149

how should IR lovastatin be taken?

Back 149

Immediate-release lovastatin requires administration with food to
assure sufficient absorption

Front 150

When are cholesterol levels at their peak?

Back 150

Diurnal rhythm of cholesterol production with maximum
cholesterol production nocturnally

Front 151

a new statin that will be marketed in 2010

Back 151

Pitavastatin (Livalo) has been approved by the FDA in 1 mg, 2 mg
and 4 mg doses; but, will not be marketed until 2010

Front 152

what are Bile Acid Sequestrants (a.k.a. Resins) effects on TG

Back 152

increase TG because they increase the production of VLDV

Front 153

what is the safest drug class in pregnancy for dyslipidemia

Back 153

bile acid sequestrants

Front 154

bile acid sequestrants place in therapy

Front 155

SE of bile acid sequestrants

Back 155

constipation and GI upset (both are common)

Front 156

monitoring for bile acid sequestrants

Back 156

Fasting lipid panel [same for all dyslipidemia drugs]

Front 157

drug interactions and bile acid sequestrants

Back 157

Colestipol and cholestyramine:
o Can directly bind other drugs and ↓ their absorption
o Should be administer 2 hr after or 2-6 hrs before other drugs
Bind acidic drugs

Front 158

what are the 2 responses to bile acid sequestrants?

Back 158

an increase in HMG CoA--> increase production of VLDL--> Increase in LDL

Increase in LDL receptors on the liver (this response dominates and therefore LDL is ultimately decreased)

Front 159

bile acid sequestrats contraindications

Front 160

bodies pharmochological changes to bile acid sequestrants

Back 160

decrease LDL (20%)
increase in TG
no change to HDL

Front 161

what are the 2 formulations of bile acid sequestrants

Back 161

Colestipol (generic, Colestid®): 2-16 gm (tabs) 1 to 2
1 gm tabs, 5 gm powder 5-30 gm (powder) 1 to 4

Cholestyramine (generic,
Questran®):
4 gm powder
4-24 gm 1 to 6

Colesevelam (WelChol®):
625 mg tabs
4-7 tabs 1 to 2

Front 162

what should you recomend to the patient when taking bile acid sequestrants?

Back 162

lots of water and fiber to prevent constipation

Front 163

what is the other FDA approved use of colesevalam

Back 163

Of note, colesevelam is also approved by the FDA to lower glucose in
patients with type 2 diabetes

doesn't cause hypoqlycemia because it is a gradual reduction

Front 164

Niacin (a.k.a. Nicotinic Acid)Place in therapy:

Front 165

physiological effects of niacin

Back 165

decrease LDL (20%)
increase HDL (best increase)
decrease TG (20-50%)

Front 166

what vitamin is niacin

Back 166

B3

Front 167

where is niacin metabolized

Back 167

liver

Front 168

SE niacin

Front 169

does the flusing casued by niacin decrease over time

Back 169

yes

Front 170

Frequency and intensity of flushing caused by niacin can be ameliorated by:

Front 171

what causes the flushing (niacin)

Back 171

release of PG D2

Front 172

comments on the niacin products that claim to be no flush

Back 172

Note: Inositol hexanicotinate is sold as “no-flush” or “flush-free” niacin, but
is does not improve lipid concentrations, appears not to be absorbed
(hence the lack of flushing) and should not be used to treat dyslipidemia

THEY DO NOT WORK

Front 173

monitoring and niacin

Front 174

should you use niacin in patients with severe or frequent gout?

Back 174

no because it increases uric acid concentrations

Front 175

drug interactions and niacin

Front 176

contraindications and niacin

Front 177

comments on niacin

Front 178

Immediate-release
[IR] (generic) niacin

Back 178

Immediate-release
[IR] (generic)
Start at 100 mg BID-TID, ↑ by 100 mg/dose weekly, target
1500-3000 mg/day. Poor tolerability, lowest hepatotoxicity.
OTC

Front 179

Slow-release [SR]
(Nicobid®, Slo-
Niacin®)

Back 179

Start at 250 mg daily, slowly ↑ by 250-500 mg/weekly,
target 1000-2000/day BID. Good tolerability, highest
hepatotoxicity risk.

Front 180

what niacin formulation hs the highest hepatotoxicity risk

Back 180

Slow-release [SR]
(Nicobid®, Slo-
Niacin®)

Front 181

Extended-release [ER]
(Niaspan®) niacin

Back 181

Start at 500 mg QHS, ↑ by 500 mg/dose weekly, target
1000-2000 mg QHS. Best tolerated, lowest
hepatotoxicity.

Rx only
Brand only

Front 182

does the metabolic by-product of niacin, nicotinamide cause hepatoxicity?

Back 182

no it is the activation of the pathway

the nonconjugated pathway

Front 183

Fibric Acid Derivatives (Fibrates) place in therapy

Front 184

pharmocological actions of fibrates

Back 184

no change in LDL
increase in HDL (20%)
decrease in TG be 50%

Front 185

how do firates work

Back 185

they inhibit the export of VLDL from the liver

Front 186

SE fibrates

Front 187

monitoring of fibrates

Back 187

Monitoring:

Front 188

drug interactions with fibrates

Front 189

statin + gemfibrozil increases risk of...

Back 189

rhabdomyolysis because utilize the same metabolic pathways
Much higher risk than fenofibrate)

Front 190

Gemfibrozil
Competitively
Competes With
Statins for UGT____ and _____

Back 190

UGT 1A1 and 1A3

Front 191

statins utilize UGT ____ and ____

Back 191

1A1 and 1A3

Front 192

fenofibrate primarily utilezes UGT ____ and ____ for metabolism

Back 192

1A9 and 2B7
this is not a primary pathway for statins so they are less interations

Front 193

is glycuronidation a CYP pathway?

Back 193

no it is a clearance pathway

Front 194

contraindications and fibrates

Back 194

Active liver disease, gallbladder disease, severe CKD (should be renally adjusted)

Front 195

comments on fibrates

Front 196

what fibrate is the safest

Back 196

fenofibrate

Front 197

dosing considerations for fibrates

Front 198

Dose fibric acid derivatives based on kidney function:

Back 198

Fenofibrate
100% of
highest
dose GFR >90)
~ 67% of
highest dose (GFR 60-90)
~ 33% of
highest dose (GFR 15-59)

Gemfibrozil
(generic, Lopid®)
600 mg BID (GFR >90)
600 mg daily (GFR 60-90)

Avoid both when GFR <15

Front 199

When do you avoid fibrates in CKD

Back 199

when gfr is less than 15 mL/min

Front 200

can serum creatinine increase while on a fibrate

Back 200

Some patients experience and increase in serum creatinine that does
not indicate kidney damage; this reverses when the fibrate is stopped

Front 201

What happens in patients with TG over 500 when they start a fibrate

Back 201

Patients with very high TG values (≥ 500 mg/dL) usually have an ↑ in LDLC
after starting a fibric acid derivative

Front 202

primary prevention

Back 202

Reducing the risk of a first CV event(s), in a patient
without a history of atherosclerotic vascular disease

No CV event has occured just trying to prevent the first event

Front 203

secondary prevention

Back 203

Reducing the risk of a CV event(s), in a patient with a
history of atherosclerotic vascular disease

trying to prevent further events

Front 204

general recommendations from AHA in CV disease prevention guidelines for primary prevention of CV events

Back 204

smoking cessation = yes
physical activity = yes
weight managment = yes
healthy eating plan = yes
BP control = yes
lipid managment = yes
DM management = yes
antiplatelet therapy = sometimes
ACE inhibitors/B-blockers = no

Front 205

general recommendations from AHA in CV disease prevention guidelines for secondary prevention of CV events

Back 205

smoking cessation = yes
physical activity = yes
weight managment = yes
healthy eating plan = no
BP control = yes
lipid managment = yes
DM management = yes
antiplatelet therapy = yes
ACE inhibitors/B-blockers = yes

Front 206

Diet and Lifestyle for CV Risk Reduction (American Heart Association, 2006): Goals

Front 207

Diet and Lifestyle for CV Risk Reduction (American Heart Association, 2006): recommendations

Front 208

Diet and Lifestyle for CV Risk Reduction (American Heart Association, 2006): physical activity

Back 208

Physical activity: Consistently encourage patients to accumulate a
minimum of 30 minutes of moderate-intensity physical activity on most,
and preferably all, days of the week

make realistic goals for the patient and start out slow

Front 209

AHA – Guidelines for CVD Prevention in Women

Back 209

Menopausal therapy - Hormone therapy and selective
estrogen-receptor modulators (SERMs) should not be used for
the primary or secondary prevention of CVD (Level A)

HRT can increase the risk of a CV event

Front 210

CONDUCTING RISK ASSESSMENT

Back 210

Initiate risk factor assessment At age 20

Front 211

Reynolds risk calculator

Back 211

Predicts: CHD, ischemic stroke, CV death
Risk factors utilized:
Sex, age, smoking, SBP, TC,
HDL, hsCRP, familial premature heart disease

Projection timeframe: 10-yr risk, and projections for advancing age

Developed: - Originally in ~25,000 women
starting in 1992, followed for
10 years
- Later in ~10,000 men starting in 1995, followed for 10 years
Other Comments:
- May better categorize women, and “moderate risk” patients
- Requires hsCRP to be drawn
- Not widely utilized as risk tool

Front 212

Frammingham risk calculator

Back 212

predicts: Hard CHD (MI or coronary death)

risk factors utilized: Sex, age, smoking, SBP, HDL

projection timeframe: 10 years

developed: 2489 men, 2856 women in Frammingham, MA.
followed for 12 years starting in 1958
Modified during ATP III

other comments:
gold standard for estimating CV risk
uncertain population similarities now vs. then

Front 213

is the reynolds risk calculator online only?

Back 213

yes

Front 214

ATP III

Back 214

the most recent guidelines (2001)

Front 215

is family hx considered in the risk factors in the frammingham calculator

Back 215

no

Front 216

is the hsCRP necessary to calculate the reynolds risk

Back 216

yes

Front 217

Emerging risk factors for inclusion in risk assessment tools:

Back 217

U.S. Preventative Services Task Force (USPSTF) - Ann Intern Med 2009 Oct
6;151(7):496-507

Front 218

JUPITER study

Back 218

o 17,802 participants from 216 countries; 5-yr study, median follow-up ~1.9 yrs

Front 219

ANTI-THROMBOTIC THERAPY

Back 219

• Antiplatelet therapy is the primary strategy to inhibit platelet aggregation and
minimize risk of thrombosis (vessel occlusion) that can occur secondary to AVD
• Platelet activation is the final step of thrombosis development in AVD
• Anticoagulant drugs (e.g., warfarin) should not be used for this particular purpose
(but might be used in patients for other indications)

doesn't reduce plaque formation just prevents final event of the clot

Front 220

should anticoagulants be used to reduce the risk of a CV event

Back 220

no antiplatelet drugs should be used

Front 221

Low-dose Aspirin

Front 222

Mechanism of Action (simplified version) of ASA

Front 223

what does ASA inhibit

Back 223

COX

Front 224

Benefits – Reducing CV Events with ASA

Front 225

the risk with ASA is...

Back 225

increased risk of bleed

Front 226

how does ASA reduce risks in men

Back 226

CV events is reduced
MI events are reduced
Stroke risk is not significantly reduced

Front 227

how does ASA reduce risks in women

Back 227

CV events is reduced
MI events are not significantly reduced
Stroke risk is reduced

Front 228

at what frammingham score should all patiens be on ASA

Back 228

greater than or equal to 10%

Front 229

when men should be on ASA based on their age and frammingham score

Back 229

age 10 year risk
45-59 > or = 4%
60-69 > or = 9 %
70-79 > or = 12%

Front 230

when women should be on ASA based on their age and frammingham score

Back 230

age 10 year risk
55-59 > or = 3%
60-69 > or = 8%
70-79 > or = 11%

Front 231

has the FDA approved the indication of ASA reducing the risk of first MI in moderate risk patients

Back 231

NO

Front 232

FDA Warns Bayer Over Claims on 2 Aspirin Products

Front 233

ASA risks

Back 233

• Bleeding related complications
o Major bleeding: Serious GI bleeding from gastric ulcers, hemorrhagic stroke,
decrease in hemoglobin ≥ 2 mg/dL
o Risk Factors for major GI bleeding from low dose aspirin:

Front 234

ASA dosing

Back 234

o Enteric coating minimizes dyspepsia, but not risk for GI toxicity
o Low-dose therapy minimizes bleeding risks

Front 235

how is a ulcer caused from ASA

Back 235

PG is inhibited

Front 236

what is the best option to reduce risk of GI blee from ASA

Back 236

PPI

Front 237

Clopridogrel (Plavix®)

Back 237

is an alternative for patients with aspirin allergy

o Inhibits platelet aggregation by inhibiting adenosine diphosphate

Front 238

Ticlopidine

Back 238

is similar to clopidogrel, but not used because of a higher risk of fatal
thrombotic thrombocytopenic purpura

Front 239

Prasugrel (Effient®)

Back 239

is a new antiplatelet agent with a similar mechanism to
clopidogrel
12
o Only indicated in acute coronary syndrome (ACS) managed with
percutaneous coronary intervention (PCI)

Front 240

Combination therapy with aspirin:

Back 240

o Not recommended in primary prevention patients because of a significant
increased risk of bleeding
o May be used in certain secondary prevention patients that have recently
experienced an acute myocardial infarction

Front 241

Omega-3 Fatty Acids proposed benefits

Back 241

o Proposed benefits:

Front 242

names of benificial omega 3 fatty acids

Back 242

EPA (eicosapentaenoic acid) & DHA (docosahexaenoic acid) shown to
confer the most benefit

Front 243

recommendations for Omega 3 fatty acids

Back 243

Primary Prevention of AVD A variety of preferably oily fish
at least twice/week

Secondary Prevention of AVD 1g/day of EPA + DHA; oily fish preferred, but supplements are an alternative

Triglyceride lowering 2-4g/day of EPA + DHA,
provided as capsules

Front 244

Resources for Omega-3 Fatty Acids & CVD:

Front 245

Antioxidant vitamins and CV risk reduction

Back 245

o Beta-carotene, Vitamin C, Vitamin E theoretically can reduce oxidation of
LDL-C and reduce atherosclerosis

Front 246

Folic Acid and CV risk reduction

Back 246

o Meta-analysis of 12 trials showed no benefit on CV events or all-cause
mortality (JAMA 2006;296:2720-6)

Back 247

o Secondary Prevention Patients: the AHA strongly recommends influenza
immunization with inactivated vaccine as a component of comprehensive care

o Immunization with live, attenuated vaccine is contraindicated for persons with cardiovascular conditions

with AVD strongly encourage, but the live vaccine is contraindicated

Front 248

PERIPHERAL ARTERIAL DISEASE (PAD)

Back 248

o A manifestation of systemic atherosclerotic vascular disease (AVD)
o Affects approximately 5 million Americans
o Many patients with PAD have not been diagnosed with this condition
o Likelihood of PAD increases in the presence of other CV risk factors
o CV disease is the cause of death in approximately 75% of patients

Front 249

Clinical presentation PAD

Back 249

o Asymptomatic initially, followed by pain and discomfort later
o Two common characteristics:

Front 250

what is the primary indicator of PAD

Back 250

Intermittent claudication

Front 251

Diagnosis PAD

Back 251

o Peripheral neuropathy, arthritis, and deep venous thrombosis must be ruled out
before diagnosing PAD
o The ankle-brachial index (ABI) is used to diagnose PAD:

ratio of different pressures
the pressures should be the same
In PAD the pressure in the ankle will be lower

Do the test on both sides of the body

Front 252

Goals of therapy PAD

Back 252

o Increase maximal walking distance, duration and pain free walking
o Control co-morbidities (e.g., hypertension, dyslipidemia, smoking, diabetes) that
increase risk of complications
o Improve quality of life

Front 253

Non-pharmacologic therapy PAD

Back 253

o Exercise (walking programs, aerobic exercise):
− Increases pain free walking
− Decreases onset of intermittent claudication
− Improves other comorbidities and/or CV risk factors
o Surgical interventions (revascularization procedures or amputation)

rehilbilitation and help regain mobility

Front 254

Pharmacotherapy PAD

Back 254

Treat specific comorbidities/CV risk factors:

Front 255

Antiplatelet therapy to reduce risk of CV events inPAD

Front 256

Pharmacotherapy for symptoms of intermittent claudication PAD

Front 257

ASA and PAD

Back 257

81–325 mg daily

Irreversibly inhibits
COX in platelets and
prevents formation
of thromboxane A2

SE: GI upset; bleeding

contraindication: bleeding
Active bleeding; hemophilia;
thrombocytopenia

Considered first line

Front 258

Clopiogrel/Plavix and PAD

Back 258

75 mg daily

Inhibits binding of
ADP analogues to
its platelet receptor
causing irreversible
inhibition of platelets

SE: Chest pain; purpura;
generalized pain;
rash

contraindication: Active pathological
bleeding (i.e., peptic ulcer,
intracranial hemorrhage)

Alternative first-line
agent when aspirin
is not tolerated or is
contraindicated

Front 259

Ticlopidine and PAD

Back 259

250 mg BID

SE: Leukopenia; rash;
thrombocytopenia;
neutropenia; agranulocytosis;
aplastic anemia

contraindications: Active bleeding; hemophilia;
thrombocytopenia

a minor player

Use clopidogrel first
due to toxicity with
ticlopidine

Front 260

Aspirin/
dipyridamole
(Aggrenox) in PAD

Back 260

25/200 mg BID

Unknown, may act
by inhibiting platelet
aggregation

SE: Angina; dyspnea;
hypotension; headache; dizziness

contraindications: Active bleeding;
ischemic heart
disease (“coronary
steal syndrome”)

no clear role

Front 261

Cilostazol
(Pletal) in PAD

Back 261

100 mg BID

Phosphodiesterase
inhibitor, suppresses
platelet aggregation;
direct artery vasodilator

SE: Fever: infection;
tachycardia

contraindications: All heart failure
patients (will
decrease survival;
is a Black Box
warning)

Improves
intermittent
claudication;
always use with an
antiplatelet agent (only used to treat symptoms)

Front 262

Pentoxifylline
(Trental) in PAD

Back 262

400 mg TID

Alters RBC flexibility;
decreases platelet
adhesion; reduces
blood viscosity;
decreases fibrinogen

SE: Dyspnea; nausea;
vomiting; headache;
dizziness

contraindications: Recent retinal or cerebral
hemorrhage; active bleeding

Good evidence
supports not using
it for intermittent
claudication (lack of
benefit)

Front 263

monitoring therapy for PAD

Back 263

(in addition to those for controlling risk factors):
o Exercise treadmill to assess walking duration, distance, pain onset
o Repeat ABI at each visit to evaluate progression of disease
o Reinforce adherence and assess for drug-related adverse effects

Front 264

in a normal myocardium

Back 264

in myocardium, preferred energy source = free fatty acids (FFAs)

ATP is used for contraction

Front 265

in a hypoxic myocardium

Back 265

ischemia → inhibition of pyruvate dehydrogenase

More FFA are utilized for energy and their by-products inhibit pyruvate DH as a result lactate is formed causing acidosis

glucose is not used as a energy source
ATP is then utilized to restore homeostasis

less ATP is avaliable for contraction

Front 266

FFA

Back 266

FFAs → more ATP/molecule than glucose BUT use more O2/ATP (15% more O2 is utilized)

FFA is less efficient than glucose

Front 267

sympathetic activation →

Back 267

TG hydrolysis--> increase FFA

cell becomes more and more reliant on FFA

Front 268

↓ glucose oxidation (myocardium)→

Back 268

↑ lactic acid formation
--> tissue acidsis
--> ATP diverted from contraction/relaxation--> ionic homeostasis

Front 269

Partial fatty acid oxidation (pfox) inhibitors

Back 269

drug-induced activation of pyruvate dehydrogenase + inhibition of fatty acid β-oxidation
→ switches substrate utilization from FFAs → glucose
--> decrease in O2 required per ATP formed, decrease lactate formation
--> increase cardiac myocyte function in ischemia (because using less 02 and lactate being formed so ATP won't be redirected to restore homeostasis

Front 270

what is the main effect of pfox inhibitors

Back 270

switch substrate utilization to glucose from FFA therefore FFA by-products do not inhibit pyruvate DH so lactate is not formed therefore more ATP for contraction and not homeostasis restoration

Front 271

new developments for CPT-1

Back 271

Companies are developing drugs that inhibit carnitine palmitoyl-transferase 1 (CPT-1), the
primary transporter for long chain FFAs into the mitochondrion, in an attempt to move ATP
formation towards glucose in ischemic myocardium

Front 272

Late sodium channel inhibitors

Back 272

Ranolazine (Ranexa)

inhibitor of late Na currents (Inal)--> prevention of Ca overloading of ischemia myocytes

Front 273

what happens to Na channels during ischemia

Back 273

• ischemia → prolonged opening of fast Na+ channels
↓ Na+/K+-ATPase activity
--> increase intracellular Na concentrations

↓ ATP availability → ↓ Ca++-ATPase activity in SR
--> increase cystolic Ca concentrations

↑ intracellular [Na+] → reversal of Na+/Ca++ exchanger
-->increase cytoslic Ca concentrations

Front 274

↑ cytosolic [Ca++]

Back 274

↑ contraction (during systole) & decrease relaxation --> increase 02 compsumption

therefore decrease coronary blood flow because blood vessels are compressed

some myocardial contraction during diastole

Front 275

SE effects of Late sodium channel inhibitors

Back 275

• dizziness
• headache
• constipation/nausea
• interacts with inhibitors of CYP3A4, e.g., diltiazem, ketoconazole, grapefruit juice
• prolongs QT interval (→ dysrhythmias (Torsades)???)

Front 276

contraindications of late sodium channel inhibitors

Back 276

liver failure

Front 277

anticoagulants

Back 277

Anticoagulants
e.g., aspirin
clopidogrel (Plavix®)
heparin (Liquaemin®)
low molecular weight heparin (enoxaparin (Lovenox®), dalteparin (Fragmin®))
• prevent thrombus formation

used for unstable angina

Front 278

ischemia

Back 278

a condition where blood flow (O2) is restricted to a part of the body
demand>supply

Front 279

cardiac ischemia

Back 279

lack of blood flow and oxygen to the heart muscle•

Front 280

Coronary Artery Disease

Back 280

• Also referred to as coronary heart disease
(CHD) or ischemic heart disease (IHD)
• Leading cause of death in both men and
women in the United States

Front 281

CAD encompasses

Back 281

– Chronic Stable Angina (CSA)
– Vasospastic angina
– Acute coronary syndrome (ACS)

Front 282

significant CAD

Back 282

– At least a 70% diameter stenosis of at least one major
epicardial artery segment
– Or > 50% stenosis of left main coronary artery

Front 283

chronic stable angina

Back 283

• Approximately 9.1 million Americans have Angina (NHIS
and NCHS 2005 data)
• Angina pectoris
– Chest pain caused most often by myocardial anoxia as a result
of occlusion of the coronary arteries from either atherosclerosis
or spasm
• Stable angina
– Chest pain or discomfort that occurs when the heart is working
harder than usual and is relieved by rest or medication
• Clinical features of CSA
– Reversibility of symptoms
– Repetitiveness of anginal attacks
– Over months to years

Front 284

3 factors of CSA

Back 284

– Reversibility of symptoms
– Repetitiveness of anginal attacks
– Over months to years

Front 285

Vasospastic angina

Back 285

Also referred to as Prinzmental’s or variant
angina
• Spasm of the coronary artery causing ischemia
– Possibly from endothelial dysfunction
– Paradoxical response to agents that normally cause
vasodilation
• Typically at rest in the early morning

different from classic because not caused by overexertion

not because of atheroscolsis

CCB can make better

Front 286

Acute coronary syndrome (ACS)

Back 286

what you are trying to prevent
• Myocardial Infarction (MI)
• Unstable Angina
– Prolonged angina at rest (> 20 minutes)
– Recent angina (within 2 months) marked limitations in
activity
– Increase in severity of Angina to CCS IV based on
symptoms

Front 287

what gender is heart disease more prevalent in

Back 287

males

NHANES study

prevalence increases with age

Front 288

what arteries does CAD usually affect

Back 288

Circumflex
left coronary artery
LAD

occasionally the right coronary artery

Front 289

Pathophysiology of CAD

Back 289

increased LDL--> fatty streaks--> plaques-->increasing plaque--> obstructive artherslerotic plaque--> plaque fissure or errosion in thrombus--> unstable angina/acute MI/death

endothelial dysfunction--> remodeling--> exertional angina

Front 290

what percentage of occlusion induces exertional angina?

Back 290

greater or = to 50-70%

Front 291

what can be changed to increase oxygen supply

Back 291

coronary blood flow
O2 extraction
O2 availability

Front 292

what can be changed to decrease O2 demand

Back 292

HR
contractility
wall tension

Front 293

Modifiable Risk factors of MI

Back 293

curent smoker
former smoker
DM
HTN
abdominal obesity
psychosocial (ie: depression)
vegatables and fruits daily
exercise
moderate alcohol intake
ApoB/ApoA ratio (5:1) (this is the biggest player ApoA--> HDL, ApoB-->LDL

Front 294

typical angina

Back 294

(definite)
– Substernal chest discomfort with a characteristic
quality and duration
– Provoked by external or emotional stress
– Relieved by rest or nitroglycerin

comes on quickly and then goes away

Front 295

atypical angina

Back 295

(probable)
– Substernal chest discomfort with a characteristic
quality and duration
– Provoked by external or emotional stress
– Relieved by rest or nitroglycerin
– Meets 2 of the above characteristics

women present in this fashion and it may be why they are under diagnosed

Front 296

noncardiac angina

Back 296

– Meets 1 or none of the typical

Front 297

Class I angina

Back 297

Ordinary physical activity does not cause angina, such as
walking and climbing stairs. Angina with strenuous or rapid or prolonged exertion at work or recreation.

Front 298

Canadian Cardiovascular Society Functional
Angina Classification

Back 298

I Ordinary physical activity does not cause angina, such aswalking and climbing stairs.

Angina with strenuous or rapid or prolonged exertion at work or recreation.

II Slight limitation of ordinary activity. Walking or climbing stairs rapidly, walking uphill, walking or stair climbing after meals, or in cold or in wind, or under emotional stress, or only during the few hours after awakening.

III Marked limitation of ordinary physical activity. Walking one or two blocks on the level and climbing one flight of stairs in
normal conditions and at normal pace.

IV Inability to carry on any physical activity without discomfort, angina symptoms may be present at rest.

Front 299

Canadian Cardiovascular Society Functional
Angina Classification

Back 299

I Ordinary physical activity does not cause angina, such aswalking and climbing stairs.

Angina with strenuous or rapid or prolonged exertion at work or recreation.

II Slight limitation of ordinary activity. Walking or climbing stairs rapidly, walking uphill, walking or stair climbing after meals, or in cold or in wind, or under emotional stress, or only during the few hours after awakening.

III Marked limitation of ordinary physical activity. Walking one or two blocks on the level and climbing one flight of stairs in
normal conditions and at normal pace.

IV Inability to carry on any physical activity without discomfort, angina symptoms may be present at rest.

Front 300

Angina class II

Back 300

Slight limitation of ordinary activity. Walking or climbing stairs
rapidly, walking uphill, walking or stair climbing after meals, or
in cold or in wind, or under emotional stress, or only during the few hours after awakening.

Front 301

Angina class III

Back 301

Marked limitation of ordinary physical activity. Walking one or
two blocks on the level and climbing one flight of stairs in
normal conditions and at normal pace.

Front 302

Angina class II

Back 302

Slight limitation of ordinary activity. Walking or climbing stairs
rapidly, walking uphill, walking or stair climbing after meals, or
in cold or in wind, or under emotional stress, or only during the few hours after awakening.

Front 303

Canadian Cardiovascular Society Functional
Angina Classification

Back 303

I Ordinary physical activity does not cause angina, such aswalking and climbing stairs.

Angina with strenuous or rapid or prolonged exertion at work or recreation.

II Slight limitation of ordinary activity. Walking or climbing stairs rapidly, walking uphill, walking or stair climbing after meals, or in cold or in wind, or under emotional stress, or only during the few hours after awakening.

III Marked limitation of ordinary physical activity. Walking one or two blocks on the level and climbing one flight of stairs in
normal conditions and at normal pace.

IV Inability to carry on any physical activity without discomfort, angina symptoms may be present at rest.

Front 304

angina class IV

Back 304

Inability to carry on any physical activity without discomfort, angina symptoms may be present at rest.

Front 305

Angina class III

Back 305

Marked limitation of ordinary physical activity. Walking one or
two blocks on the level and climbing one flight of stairs in
normal conditions and at normal pace.

Front 306

Canadian Cardiovascular Society Functional
Angina Classification

Back 306

I Ordinary physical activity does not cause angina, such aswalking and climbing stairs.

Angina with strenuous or rapid or prolonged exertion at work or recreation.

II Slight limitation of ordinary activity. Walking or climbing stairs rapidly, walking uphill, walking or stair climbing after meals, or in cold or in wind, or under emotional stress, or only during the few hours after awakening.

III Marked limitation of ordinary physical activity. Walking one or two blocks on the level and climbing one flight of stairs in
normal conditions and at normal pace.

IV Inability to carry on any physical activity without discomfort, angina symptoms may be present at rest.

Front 307

angina class IV

Back 307

Inability to carry on any physical activity without discomfort, angina symptoms may be present at rest.

Front 308

SAQ (seattle angina questionare) angina classifications

Back 308

minimal
mild
moderate
severe--> over 2 year period mortality rate increases by 20%

Front 309

Angina class II

Back 309

Slight limitation of ordinary activity. Walking or climbing stairs
rapidly, walking uphill, walking or stair climbing after meals, or
in cold or in wind, or under emotional stress, or only during the few hours after awakening.

Front 310

Angina class II

Back 310

Slight limitation of ordinary activity. Walking or climbing stairs
rapidly, walking uphill, walking or stair climbing after meals, or
in cold or in wind, or under emotional stress, or only during the few hours after awakening.

Front 311

Canadian Cardiovascular Society Functional
Angina Classification

Back 311

I Ordinary physical activity does not cause angina, such aswalking and climbing stairs.

Angina with strenuous or rapid or prolonged exertion at work or recreation.

II Slight limitation of ordinary activity. Walking or climbing stairs rapidly, walking uphill, walking or stair climbing after meals, or in cold or in wind, or under emotional stress, or only during the few hours after awakening.

III Marked limitation of ordinary physical activity. Walking one or two blocks on the level and climbing one flight of stairs in
normal conditions and at normal pace.

IV Inability to carry on any physical activity without discomfort, angina symptoms may be present at rest.

Front 312

SAQ (seattle angina questionare) angina classifications

Back 312

minimal
mild
moderate
severe--> over 2 year period mortality rate increases by 20%

Front 313

Angina class III

Back 313

Marked limitation of ordinary physical activity. Walking one or
two blocks on the level and climbing one flight of stairs in
normal conditions and at normal pace.

Front 314

Angina class II

Back 314

Slight limitation of ordinary activity. Walking or climbing stairs
rapidly, walking uphill, walking or stair climbing after meals, or
in cold or in wind, or under emotional stress, or only during the few hours after awakening.

Front 315

Angina class III

Back 315

Marked limitation of ordinary physical activity. Walking one or
two blocks on the level and climbing one flight of stairs in
normal conditions and at normal pace.

Front 316

Angina class III

Back 316

Marked limitation of ordinary physical activity. Walking one or
two blocks on the level and climbing one flight of stairs in
normal conditions and at normal pace.

Front 317

angina class IV

Back 317

Inability to carry on any physical activity without discomfort, angina symptoms may be present at rest.

Front 318

angina class IV

Back 318

Inability to carry on any physical activity without discomfort, angina symptoms may be present at rest.

Front 319

SAQ (seattle angina questionare) angina classifications

Back 319

minimal
mild
moderate
severe--> over 2 year period mortality rate increases by 20%

Front 320

angina class IV

Back 320

Inability to carry on any physical activity without discomfort, angina symptoms may be present at rest.

Front 321

SAQ (seattle angina questionare) angina classifications

Back 321

minimal
mild
moderate
severe--> over 2 year period mortality rate increases by 20%

Front 322

Canadian Cardiovascular Society Functional
Angina Classification

Back 322

I Ordinary physical activity does not cause angina, such aswalking and climbing stairs.

Angina with strenuous or rapid or prolonged exertion at work or recreation.

II Slight limitation of ordinary activity. Walking or climbing stairs rapidly, walking uphill, walking or stair climbing after meals, or in cold or in wind, or under emotional stress, or only during the few hours after awakening.

III Marked limitation of ordinary physical activity. Walking one or two blocks on the level and climbing one flight of stairs in
normal conditions and at normal pace.

IV Inability to carry on any physical activity without discomfort, angina symptoms may be present at rest.

Front 323

SAQ (seattle angina questionare) angina classifications

Back 323

minimal
mild
moderate
severe--> over 2 year period mortality rate increases by 20%

Front 324

Angina class II

Back 324

Slight limitation of ordinary activity. Walking or climbing stairs
rapidly, walking uphill, walking or stair climbing after meals, or
in cold or in wind, or under emotional stress, or only during the few hours after awakening.

Front 325

Angina class III

Back 325

Marked limitation of ordinary physical activity. Walking one or
two blocks on the level and climbing one flight of stairs in
normal conditions and at normal pace.

Front 326

angina class IV

Back 326

Inability to carry on any physical activity without discomfort, angina symptoms may be present at rest.

Front 327

SAQ (seattle angina questionare) angina classifications

Back 327

minimal
mild
moderate
severe--> over 2 year period mortality rate increases by 20%

Front 328

Non-Atherosclerotic Causes of Chest Pain

Back 328

non-cardiac
anxiety
GERD
PE
must rule these out

Front 329

treatement goals of angina

Front 330

ACC/AHA Evidence Based Medicine Ranking
Criteria classes

Back 330

I Conditions for which there is evidence or general agreement that a given procedure or treatment is useful and effective.

II Conditions for which there is conflicting evidence or a divergence of opinion
about the usefulness/efficacy of a procedure or treatment.

IIa Weight of evidence/opinion is in favor of usefulness/efficacy. (RTC lots of trials)

IIb Usefulness/efficacy is less well established by evidence/opinion. (few clinical trials and mixed results)

III Conditions for which there is evidence that the procedure/treatment is not
useful/effective and in some cases may be harmful.
(expert opinions)

Front 331

ACC/AHA Evidence Based Medicine Ranking
Criteria levels

Back 331

A Data from multiple randomized clinical trials with large patients populations.

B Data from a limited number of randomized trials, small patient populations,
careful analyses of nonrandomized studies, or observational registries.

C Expert consensus was the primary basis for the recommendation

Front 332

Hemodynamic Effects of Anti-Ischemic Medications B-blockers

Back 332

decrease **heart rate, decrease systolic pressure, increase leftm ventricular volume, decrease contractility

Front 333

Hemodynamic Effects of Anti-Ischemic Medications nitrates

Back 333

increase HR, decrease systolic pressure, **decrease left ventricular volume, no change in contractility

Front 334

Hemodynamic Effects of Anti-Ischemic Medications dihydropyridines CCB

Back 334

increase HR, ** decrease systolic pressure, no change or decrease in left ventricular volume

Front 335

Hemodynamic Effects of Anti-Ischemic Medications non-dihydropyrindines

Back 335

** decrease HR, decrease systolic pressure, no change or decrease in left ventricular volume, no change or decrease in contractility

Front 336

Hemodynamic Effects of Anti-Ischemic Medications ranolazine

Back 336

no change in HR, systolic pressure, left ventricular volume, no change or increase in contraction

Front 337

beta-blockers

Back 337

• First line for chronic stable angina
• Decrease myocardial oxygen consumption by ↓ HR, ↓
BP, ↓ myocardial contractility
• Can use cardioselective or non-selective agents
– Cardioselective (preferred): Metoprolol, atenolol, bisoprolol
– Non-cardiosective: Propranolol, nadolol
• Never use agents with intrinsic sympathomimetic activity
(ISA) such as acebutolol
• Key points of beta-blockade therapy
– Need enough blockade to blunt the HR response when
physiologically stressed
– Sufficient blockade results in optimal ↓ cardiac demand
– Side effects can limit the ability to titrate the dose
– Low doses are better than no doses

Front 338

key points b-blockers

Back 338

– Need enough blockade to blunt the HR response when
physiologically stressed
– Sufficient blockade results in optimal ↓ cardiac demand
– Side effects can limit the ability to titrate the dose
– Low doses are better than no doses

Front 339

b-blocker survival benefit

Back 339

6% reduction in 2nd MI or myocardial death

Front 340

selective beta blockers

Back 340

atenolol
metoprolol
bisoprolol

Front 341

non-selective b-blockers

Back 341

carvediolol

Front 342

how many times a day is atenolol doses for beta receptor blockade

Back 342

bid

Front 343

ACC/AHA 2007 Recommendations B-blockers

Back 343

Class I recomendations

Beta-blockers as initial therapy in the absence of contraindications in all patients who have had a myocardial infarction (MI), acute coronary syndrome (ACS), or Left ventricular systolic dysfunction
(LVSD) with or without heart failure (HF) symptoms
( level A)

In hypertensive patients with CAD it is appropriate to treat initially with beta-blockers and ACE inhibitors (ACE-I) and then add other medications to achieve target blood pressure goals (level C)

Front 344

CCBs

Back 344

• First line for vasospastic angina
• MOA
– Dilate coronary and systemic arteries
– ↑ coronary blood flow
– ↓ myocardial oxygen consumption

best vesodilators, decreae demand on heart

Front 345

dihydropyridines CCB

Back 345

– Can be safely used in combination with beta-blocker therapy
– Do not use immediate release nifedipine for CSA
– Medications: Nifedipine, amlodipine

Front 346

non-dihydropyridiness CCB

Back 346

Avoid use in combination with beta-blocker therapy (↓ HR)
– Medications: Diltiazem, verapamil

Front 347

DCCB pharmacologic effects

Back 347

Amlodopine
increase or no change in HR and contractility, increase ** vascular dilation, increase coronary flow, increase or no change in neurohormonal activation

Nifidipine
increase HR, increase or no change in contractility, increase in neurohormonal activation, increase ** in vascular dilation, increase coranary flow

Front 348

NDCCB pharmacological effects

Back 348

Diltiazem
decrease HR and contractility, increase in neurohormanal activation, vascular dilation, coronary flow

verapamil
decrease in HR, ** decrease contractility, increase in neurohormanal activation, vascular dilation, coronary flow

Front 349

ACC/AHA 2002 Recommendations CCB

Back 349

class I recommendations

CCBs (never immediate release nifedipine) and/or long-acting
nitrates for reduction in symptoms when beta-blockers are
contraindicated (level B)

CCB and/or long-acting nitrates in combination with beta-blockers
when initial treatment with beta-blocker alone is not successful (level B)

CCBs and/or long-acting nitrates as a substitute for beta-blockers if
initial treatment with beta-blockers leads to unacceptable side effects
(level C)

Class IIa recomendations
Long-acting nondihydropyridine CCB instead of beta-blockers
as initial therapy
(level B)

Front 350

nitrates

Back 350

• First line as needed for immediate relief of angina
• Second to Third line for chronic maintenance therapy for stable
angina
• Dilate systemic and coronary arteries resulting in venous pooling of blood (↓ cardiac work and chamber size)
• Contraindicated with PDE-5 inhibitors (e.g., sildenafil, vardenafil, tadalafil) extreme hypotension
• Key points of quick acting nitroglycerin (NTG)
– Sublingual tablets most frequently used (buccal or lingual spray available)
– 75% have pain relief in 3 minutes
– 15% have relief in 5 to 15 minutes
– Directions
• Dissolve 1 SL tablet (0.4 mg) under tongue or in buccal pouch at the first sign of an anginal attack
• If symptoms have not improved after 5 minutes emergency medical
services (EMS) should be contacted
• Continue to take additional SL tablets until EMS arrives (1 tablet every five minutes up to a total of 3 tablets)

ususally add ons to chronic therapy
quickly vasodilates
new bottle every 6 months

Front 351

chronic nitrate therapy

Back 351

Key points of chronic maintenance nitrate
therapy
– Available in immediate release, sustained
release, and transdermal products
– Nitrate Tolerance
• Develops with chronic use
• Mechanism is debated
– All patients on chronic nitrate therapy need a
nitrate free period of at least 8 hours (12 hours is best)

used in addition to CCB or B-therapy

Front 352

Nitrate products

Back 352

Nitroglycerine (SL, Buccal, spray, Ointment, IV, patch, oral sustained release)

isoosorbide dinitrate (oral and sustained release)

isosorbide mononitrate (oral and sustained release)

Front 353

ACC/AHA 2002 Recommendations nitrates

Back 353

class I recomendations

Sublingual NTG or NTG spray for the immediate relief of angina (level B)

CCBs (never immediate release nifedipine) and/or long-acting
nitrates for reduction in symptoms when beta-blockers are
contraindicated
(level B)
CCB and/or long-acting nitrates in combination with beta-blockers
when initial treatment with beta-blocker alone is not successful
(level B)
CCBs and/or long-acting nitrates as a substitute for beta-blockers if
initial treatment with beta-blockers leads to unacceptable side effects
(level C)

Front 354

ranolazine MOA

Back 354

inhibits the late inward NA current preventing Na and CA overload resulting in diastolic relaxation

effects the cardiac cycle

Front 355

ranolazine trials

Back 355

• MARISA
– Primary Outcome
• Increase in exercise duration time
• CARISA
– Primary Outcomes
• Increase in exercise duration time
• Delayed time to angina symptoms
• Delayed time to ST depression
– Secondary Outcomes
• Reduction in angina episodes per week
• Reduction in nitroglycerin (NTG) use per week

• ERICA
– Angina Episodes per week
– NTG use per week
• MERLIN-TIMI-36 (long term)
– No difference in Primary CV composite endpoint
– Recurrent Ischemia
• 16.1% placebo vs. 13.9% ranolazine (p = 0.03)
– Arrhythmia on Holter monitor
• 83.1% placebo vs. 73.1% ranolazine (p < 0.001)
• ROLE
– No significant ECG changes
– Most common ADE’s: dizziness, constipation, peripheral edema

Front 356

ACC/AHA 2007 Recommendations ranolazine

Back 356

there are no recomendations for the use of ranolazine

Class IIB recomendations
Metabolic agents (e.g., ranolazine) may be used where available as
add on therapy, or as substitution therapy when conventional drugs
are not tolerated
(level B)

Front 357

ranolazine

Back 357

• Indicated for
– CSA patients
– On beta-blockers and/or CCBs and nitrates
– Symptomatic
• Inhibits the late inward sodium channel
• Optimal Patients
– Intolerance to beta-blockers
– Patients with low heart rates or blood
pressures
• Avoid use with concomitant medications known
to prolong QTc Intervals
• Dosing: 500 mg po BID (Max 1000 mg po BID)

add on therapy

Front 358

developement of ischemia causes

Back 358

↑ O2 demand
• Heart rate
• Blood pressure
• Preload
• Contractility
↓ O2 supply

all of the above causes Ca overload

use B-blockers, nitrates and CCB to prevent

Front 359

consequences of ischemia

Back 359

• Electrical instability
• Myocardial dysfunction
(↓systolic function/
↑ diastolic stiffness)

all of the above causes compression of nutritive blood vessels

Front 360

CSA Dx-->

Back 360

treat with a b-blocker and if symptoms presist treat with long acting nitrate or CCB and if symtops still presist add the opposite of previosly added and then consider revascularization

all patients should be on NTG PRN

all meds should be titrated up before adding another agent

All patients should be on ASA

Front 361

antiplatelet therapy

Back 361

• ACC/AHA Recommendation in 2007:
– ASA 75 – 162 mg daily for patients with CSA
• American College of Chest Physicians
Recommendation:
– ASA 75 – 162.5 mg daily for patients with CSA
• Antithrombotic Trialists’ Collaboration:
– 7 clinical trials in CSA/CAD
– 144/1448 (9.8%) vs. 208/1472 (14.1%) of vascular
events in antiplatelet treated vs placebo, respectively

Front 362

CAPRIE trial

Back 362

Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events;
no change in events

Front 363

CURE trial

Back 363

Clopidogrel in Unstable Angina to Prevent
Recurrent Events;

no change in events

Front 364

MATCH trial

Back 364

Management of Atherothrombosis with Clopidogrel in High-risk Patients;

Front 365

CHARISMA trial

Back 365

Clopidogrel and
Aspirin versus Aspirin Alone for the Prevention of Atherothrombotic Events;

Front 366

palvix + ASA

Back 366

doubled the risk of bleeding in the CHARISMA trial

Front 367

ACC/AHA 2007 Recommendations ASA

Back 367

class I recommendations

Aspirin 75 to 162 mg in the absence of contraindications (level A)
Use of warfarin in conjunction with aspirin and/or clopidogrel is associated with an increase risk of bleeding and needs to be closely monitored (level B)

Class II a recommnedations
Clopidogrel when aspirin is absolutely contraindicated (level B)

class IIb recommendations
Low-intensity anticoagulation with warfarin in addition to aspirin (level B)

Front 368

Lipid-lowering Therapy

Back 368

• All patients with CAD should be on LDL-C
lowering therapy to reduce risk of CV
events
• Statin therapy is preferred
– Capable of a 30-40% LDL-C reduction

If baseline LDL-C is < 100 mg/dL still start
statin therapy unless contraindicated

Front 369

NCEP ATP III Goals (2004 Update) cholesterol

Back 369

very high risk LDL < 70
High risk LDL < 100

Front 370

ACC/AHA 2007 Recommendations dyslipidemia

Back 370

class I recomendations

Low density lipoprotein cholesterol (LDL-C) lowering therapy should
be targeted to a goal of at least < 100 mg/dL and if on the treatment LDL-C is > 100 mg/dL then therapy should be intensified
(level A)
In moderate to high-risk patients using LDL-C lowering therapy it is recommended to use therapy capable of achieving a 30-40%
reduction in LDL-C levels (level A)
Daily physical activity and weight management are recommended for
all patients (level B)
Dietary therapy for all patients should include intake of saturated fats (<7% total calories), trans-fatty acids, and < 200 mg cholesterol daily)
(level B)
Triglycerides (TG) are 200 to 499 mg/dL then non-HDL-C <130 mg/dL (level B)
TGs > 500 mg/dL therapeutic options to lower TGs (niacin or fibrates) should be initiated prior to LDL-C targeted therapy with a non-HDL-C goal of < 130 mg/dL
(level C)
Drug combinations are beneficial for patients on lipid lowering therapy who are not able to achieve and LDL-C < 100 mg/dL
(level C)

Class IIa recomendations
Reasonable to target LDL-C to < 70 mg/dL or use high-dose statins (level A)
If choose a LDL-C goal of < 70 mg/dL then titrate drug to achieve this goal taking in account possible S/Es and cost. If goal of < 70 mg/dl is
not achievable based on initial LDL-C levels then target a 50% ↓ (level C)
Baseline LDL-C is 70 to 100 mg/dL it is reasonable to treat to a LDL-C goal of < 70 mg/dL
(Level B)
Adding plant stanol/sterols (2gm/d) and/or viscous fiber (>10 gm/d) is reasonable to further lower LDL-C (level A)
TGs are 200 to 499 mg/dL then it is reasonable to target a non-HDL-C of < 100 mg/dL
(level B)
Therapeutic options to reduce non-HDL-C (after LDL-C lowering therapy) are Niacin or Fibrates
(level B)

Front 371

ACC/AHA 2007 Recommendations ASA

Back 371

class I recommendations

Aspirin 75 to 162 mg in the absence of contraindications (level A)
Use of warfarin in conjunction with aspirin and/or clopidogrel is associated with an increase risk of bleeding and needs to be closely monitored (level B)

Class II a recommnedations
Clopidogrel when aspirin is absolutely contraindicated (level B)

class IIb recommendations
Low-intensity anticoagulation with warfarin in addition to aspirin (level B)

Front 372

ACE-Is role in preventing CV events

Back 372

• The ACC/AHA 2002 guidelines recommended:
– ACE-I’s in patients with CAD or other vascular disease (Class
IIa, Level B)
– Recommendation based on HOPE trial
• Two major clinical trials not included in the 2002 guidelines were
assessed for the 2007 guidelines:
– EUROPA
– PEACE
• An exact mechanism of action that explains the benefit of ACE-I
therapy in CSA is unknown
– Inhibition of ACE results in
• Vasodilation
• Diuresis
• Anti-remodeling

Front 373

Lipid-lowering Therapy

Back 373

• All patients with CAD should be on LDL-C
lowering therapy to reduce risk of CV
events
• Statin therapy is preferred
– Capable of a 30-40% LDL-C reduction

If baseline LDL-C is < 100 mg/dL still start
statin therapy unless contraindicated

Front 374

NCEP ATP III Goals (2004 Update) cholesterol

Back 374

very high risk LDL < 70
High risk LDL < 100

Front 375

ACC/AHA 2007 Recommendations dyslipidemia

Back 375

class I recomendations

Low density lipoprotein cholesterol (LDL-C) lowering therapy should
be targeted to a goal of at least < 100 mg/dL and if on the treatment LDL-C is > 100 mg/dL then therapy should be intensified
(level A)
In moderate to high-risk patients using LDL-C lowering therapy it is recommended to use therapy capable of achieving a 30-40%
reduction in LDL-C levels (level A)
Daily physical activity and weight management are recommended for
all patients (level B)
Dietary therapy for all patients should include intake of saturated fats (<7% total calories), trans-fatty acids, and < 200 mg cholesterol daily)
(level B)
Triglycerides (TG) are 200 to 499 mg/dL then non-HDL-C <130 mg/dL (level B)
TGs > 500 mg/dL therapeutic options to lower TGs (niacin or fibrates) should be initiated prior to LDL-C targeted therapy with a non-HDL-C goal of < 130 mg/dL
(level C)
Drug combinations are beneficial for patients on lipid lowering therapy who are not able to achieve and LDL-C < 100 mg/dL
(level C)

Class IIa recomendations
Reasonable to target LDL-C to < 70 mg/dL or use high-dose statins (level A)
If choose a LDL-C goal of < 70 mg/dL then titrate drug to achieve this goal taking in account possible S/Es and cost. If goal of < 70 mg/dl is
not achievable based on initial LDL-C levels then target a 50% ↓ (level C)
Baseline LDL-C is 70 to 100 mg/dL it is reasonable to treat to a LDL-C goal of < 70 mg/dL
(Level B)
Adding plant stanol/sterols (2gm/d) and/or viscous fiber (>10 gm/d) is reasonable to further lower LDL-C (level A)
TGs are 200 to 499 mg/dL then it is reasonable to target a non-HDL-C of < 100 mg/dL
(level B)
Therapeutic options to reduce non-HDL-C (after LDL-C lowering therapy) are Niacin or Fibrates
(level B)

Front 376

ACE-Is role in preventing CV events

Back 376

• The ACC/AHA 2002 guidelines recommended:
– ACE-I’s in patients with CAD or other vascular disease (Class
IIa, Level B)
– Recommendation based on HOPE trial
• Two major clinical trials not included in the 2002 guidelines were
assessed for the 2007 guidelines:
– EUROPA
– PEACE
• An exact mechanism of action that explains the benefit of ACE-I
therapy in CSA is unknown
– Inhibition of ACE results in
• Vasodilation
• Diuresis
• Anti-remodeling

Front 377

ACE Inhibitor Mechanism of Action

Back 377

inhibits angiotensin I from going to angiotensin II
therefore increases vasodilation, Increase bradikinin, increases NO, natriu.diuresis, anti-remoldeling

actions through AII receptor anit-proliferation, cell defferntiation, and tissue repair

Front 378

Myocardial Tissue Seletivity ACE-Is

Back 378

Quinapril > benazepril > ramipril > perindopril
> lisinopril > trandolapril > enalapril >fosinopril > captopril

HOPE=ramipril
EUROPA= perindopril
PEACE= trandolapril

Front 379

What trial had the best managed patients in regards to ACE

Back 379

PEACE
therefore ability to prove benefits was less likely

Front 380

HOPE trial (ACE)

Back 380

14.0% ramipril
vs. 17.8%
placebo
(p < 0.001)

all patients should have been on ASA only 76% were

it was easier to show benefits of therapy because patients were poorly managed

Primary outcomes
CV death, nonfatal MI, stroke

Front 381

EUROPA trial (ACE)

Back 381

again poorly managed patients

primary outcomes
CV death, nonfatal MI, cardiac arrest with successful resuscitation
8.0%
perindopril vs.
9.9% placebo
(p = 0.003)

Front 382

PEACE trail (ACE)

Back 382

best managed pateints so hard to show benefits

primary outcomes
CV death, nonfatal MI, revascularization

Front 383

ACC/AHA 2007 Recommendations ACE

Back 383

Class I recomendations

with beta-blockers and ACE inhibitors (ACE-I) and then add other medications to achieve target blood pressure goals
(level C)
ACE-Is in all patients with left ventricular ejection fraction (LVEF) < 40% and in those with hypertension, diabetes, or chronic kidney disease (CKD)
(level A)
ACE-Is in all patients unless considered low risk (LVEF > 40% with well controlled cardiovascular (CV) risk factors and s/p
revascularization)
(level B)

Class IIa recomendations
ACE-I in low risk patients with mildly reduced or normal LVEF in whom
CV risk factors are not controlled and revascularization has not been
performed (level B)

Front 384

ONTARGET trial

Back 384

showed that ARBS are just as good as ACEs, but do not use in combination

Front 385

ACC/AHA 2007 Recommendations ARBS

Back 385

class I recomendations

Angiotensin receptor blockers (ARB) are recommended for patients
who have hypertension, have indications for but are intolerant to ACE-I, have heart failure, or have had a MI with and LVEF < 40% (level A)

class IIB recommendation
ARBs may be considered in combination with ACE-Is for HF due to LVSD (level B)

Front 386

Can CCB therapy prevent CV
events in patients with CSA
either as initial therapy or as
add on therapy?

Back 386

• Three major clinical trials not included in the 2002 guidelines were
assessed for the 2007 guidelines:
– ACTION
– CAMELOT
– INVEST
• Mechanism of action that explains the benefit of CCB therapy in
decreasing atherosclerotic formation is not well developed
• Thought to be related to improvement in endothelial nitric oxide
release, resulting in the avoidance of atheroma formation in the
vessels
– CAMELOT only positive study
– Limitations of study comparison secondary to patient populations
included in each study and differences in primary endpoints

Front 387

is there evidence to supprt CCB role to prevent CSA events

Back 387

no they are used in CSA to treat symptoms

Front 388

ACC/AHA 2002 Recommendations CCB

Back 388

class I recommendations

CCBs (never immediate release nifedipine) and/or long-acting nitrates for reduction in symptoms when beta-blockers are contraindicated
(level B)
CCB and/or long-acting nitrates in combination with beta-blockers when initial treatment with beta-blocker alone is not successful (level B)
CCBs and/or long-acting nitrates as a substitute for beta-blockers if initial treatment with beta-blockers leads to unacceptable side effects (level C)

class IIa recomendations
Long-acting nondihydropyridine CCB instead of beta-blockers
as initial therapy
(level B)

Front 389

is dipyridamole recommended for CSA

Back 389

no

Front 390

is chelation therapy recommended for CSA

Back 390

no

Front 391

ACC/AHA 2002 Recommendations others for CSA

Back 391

class I recommendations

Blood pressure goals according to JNC-7 of < 140/90 mmHg or
< 130/80 mmHg for patients with diabetes or chronic kidney disease
(level A)
Aldosterone blockade is recommended for use in post-MI patients without significant renal dysfunction (Scr < 2.5 mg/dL in men and
< 2.0 mg/dL in women) or hyperkalemia (K+ < 5.0 mEq/L) who are already receiving therapeutic doses of an ACE-I or beta-blocker, have LVEF < 40%, and have either Diabetes or HF
(level A)
Annual influenza vaccine in all patients with Cardiovascular disease (level B)

Front 392

COURAGE trial

Back 392

• Treatment Arms:
– PCI (+/- stent) + Optimal
Medical Therapy (OMT)
– OMT alone
• Eligible patients:
– Stable CAD
• CCS I-III Angina
• Stable post MI
• Asymptomatic with objective
myocardial ischemic findings
• Primary Endpoint
(Composite):
– Nonfatal MI
– All-cause mortality
• Median follow-up: 4.6 years

stable CAD patients
these were maximally mangaed patients

Front 393

Optimal Medical Therapy CSA

Back 393

• Antiplatelet therapy
– ASA 81 – 325 mg/day or
– Clopidogrel 75 mg/day
(on both if had PCI)
• Angina medications (Alone or in combination)
– Metoprolol succinate
– Amlodipine
– Isosorbide mononitrate
• Angiotensin blocking therapy
– Lisinopril or
– Losartan
• Lipid lowering therapy
– Simvastatin +/- ezetimibe
– Goal LDL-C level of 60 to 85 mg/dL
– Following LDL-C goal achievement went to secondary goal of raising
HDL-C (Exercise, niacin ER, and fibrate alone or combination)

very aggressive treatment

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COURAGE: Cumulative Event Outcomes

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Death, MI was not significant

revascularization was significant

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Pharmaceutical Care Card for CSA

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A = Aspirin and Antianginal therapy
B = Beta-blocker and Blood pressure
C = Cigarette smoking and Cholesterol
D = Diet and Diabetes
E = Education and Exercise

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medication monitoring CSA

Back 396

Gage the effectiveness of therapy
– Vital Signs
– Use of sublingual nitroglycerin (refills?, weekly use?)
– Adverse effects
– Electrocardiogram if needed
– Exercise tolerance testing has limited value (b-blocker will reduces ability, gives idea of stenosis)

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b-blocker target HR for CSA

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55-70 bpm

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in the liver cholesterol is converted too...

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cholic acid a bile acid that is abundant

adds a COOH group to cholesterol

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what are signs of avd?

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PAD
Coronary artery disease (angina, MI, sudden cardiac death)
Symptomatic Carotid artery disease (stroke, TIA)
Abdominal aortic aneurysm

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when do you use ASA in primary prevention patients

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when farmingham score is > or = 10%

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primary prevention of avd patients and omega-3

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a variet of preferably oily fish at least 2/weekly

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secondary prevention of avd and omega-3

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1g/day of epa+dha; oily fish preferred but supplements are an alternative

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TG lowering for avd and omega-3

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2-4g/day of epa+dha, provided as capsules