Ios Exam 3

Front 1

Ezetimbe
What is it?
Place in Therapy

Back 1

Cholesterol Absorption Inhibitor

Add-on to statin therapy for LDL-C reduction; monotherapy for patients with contraindications or statin intolerance

No outcomes data are available

Front 2

Ezetimbe side effects

Front 3

Ezetimbe Monitoring

Front 4

Ezetimbe Contraindications

Back 4

NONE

Front 5

Ezetimbe general info:

Front 6

Ezetimbe with simvastatin (Vytorin)

Back 6

• Same as ezetimibe (Zetia®) with simvastatin (Zocor®)
• Available in 10/10 mg, 10/20 mg, 10/40 mg, and 10/80 mg tablets
• Usual starting dose: 10/20 mg or 10/40 mg daily in the evening

Front 7

Fixed dose Niacin with statin:
Advicor
Simcor

Back 7

Advicor: extended release niacin(Niaspan) with lovastatin

Simcor: extended release naicin(Niaspan) with simvastatin

Front 8

Key Points:
Omega 3 fatty acids (FAs)

Back 8

• Docosahexaenoic acid (DHA) & Eicosapentaenoic acid (EPA) are only 2 omega-
3 fatty acids with cardiovascular benefits
• Both DHA and EPA are equally on a mg-per-mg basis
• Alpha linoleic acid is technically an omega-3, but does not have CV benefits
• Used to provide TG lowering and non-HDL reductions
• If TG ≥ 500 mg/dL might have an ↑ in LDL-C when treated with omega-3 FA
• No increased risk of systemic toxicity when used with a statin

Front 9

Prescription FA:
Lovaza

Back 9

o Each 1 g capsule contains 465 mg EPA and 375 mg DHA
o FDA approved for hypertriglyceridemia
o Dosing is 4 caps/day given once daily or BID with food (this dose provides
3360 mg omega-3 fatty acids daily)
o Do not freeze these capsules

Front 10

OTC Fish Oil products
(nutritional supplements)

Back 10

o Typical products: 1 g contains 120 mg DHA and 180 mg EPA, the
remaining content is remnant fish oils
o Other higher potency products are available
o Use a product that is “USP-Verified”
o Freezing or using enteric coated OTC fish oil products minimizes
dyspepsia/fishy smelling belching
o Dosing on OTC label will not lower TG values; higher doses are needed

Front 11

Omega 3 FA dosing

Back 11

based on total amt. EPA and DHA

For:
TG lowering: 2-4 g daily

CV risk reduction in AVD pts: 1 g daily

Front 12

Starting dyslipidemia drug therapy:

Back 12

o Select rational initial doses based on LDL-C reductions needed
o Titrate dose up and/or add an additional agent to achieve targets
o For niacin, titrate dose up slowly to maximize tolerability
o TLC is appropriate for all patients to augment effects of drug therapy

Front 13

Patient Education for dyslipidemia therapy

Back 13

o Highlight the long-term benefits of therapy
o Describe appropriate use and special dosing considerations
o Describe realistic expectation of side effects
o Educate regarding precautions for myalgia depending on the regimen
o Explain and encourage TLC

Front 14

High LDL-C
monotherapy and comination regimen options

Back 14

Monotherapy:
statin
ezetimbe
niacin
bile acid sequestrant

Combinations:
statin + ezetimbe
statin + bile acid seq.
statin + niacin (higher risk systemic toxicity)
niacin + bile acid seq.

Front 15

Mixed dyslipidemia
(High LDL-C, high TGs)
monotherapy and comination regimen options

Back 15

Monotherapy:
statin(high dose needed)
niacin

Combinations:
statin + fibrate (higher risk systemic toxicity)
statin + niacin (higher risk systemic toxicity)
bile acid seq. + niacin

Front 16

High TGs
monotherapy and comination regimen options

Back 16

Monotherapy:
fibrate
niacin
fish oil

Combination:
fibrate + statin (higher risk systemic toxicity)
fibrate + niacin (higher risk systemic toxicity)
Fibrate + omega 3 FA
Niacin + statin (higher risk systemic toxicity)
niacin + omega 3 FAs
omega 3 FAs + statin

Front 17

Hypertryglyceridemia

Front 18

Combination therapy key points:
dyslipidemia

Front 19

Metabolic Syndrome Criteria

Back 19

3 of 5 needed to diagnose MetSyn:

1. Abdominal Obesity
o Waist circumference ≥ 40” for men, ≥ 35” for women (lower in Southeastern Asian
populations)

2. High Triglycerides
o ≥ 150 mg/dL or drug treatment for elevated TGs

3. Low HDL-C
o < 40 mg/dL (men), < 50 mg/dL (women), or drug treatment for low HDL-C

4. Elevated Blood Pressure
o ≥ 130/≥ 85 mmHg, or drug treatment for hypertension

5. Elevated fasting glucose
o ≥ 100 mg/dL, or drug treatment for hyperglycemia

Tertiary Targets (HDL-C goals) apply to these patients after attaining both primary and secondary targets

Front 20

Diabetic Dyslipidemia
Type 2 diabetes

Back 20

“Diabetic Dyslipidemia” (a.k.a. atherogenic dyslipidemia):

Front 21

Diabetic Dyslipidemia
Treatment and goals

Back 21

Nearly all should be on a statin:

Front 22

Mechanisms by Which Diet Potentially Influences Risk of Coronary Heart Disease

Back 22

DIET
-->
INTERMEDIARY BIOLOGICAL MECHANISMS:
1. Lipid levels-HDL, LDL, TG, lipoproteins
2. BP
3. Thrombotic Tendency
4. cardiac rhythm
5. endothelial function
6. systemic inflammation
7. insulin sensitivity
8. oxidative stress
9. homocysteine level
-->
RISK OF CORONARY HEART DISEASE

Front 23

Coronary Heart Disease (CHD) Lifestyle
Risk Factors:

Back 23

Risk Factors:
– Obesity
– High waist circumference
• Men: >42”
• Women: >35”
– Physical Inactivity
– Diet high in saturated & trans fat

Front 24

Weight Loss Effect on Lipids

Back 24

• Weight loss will have profound affect on
lowering lipids, independent of
macronutrient composition of diet
(negative energy balance).
• High waist circumference (visceral fat)
highly correlated with CHD & Type 2
diabetes

Front 25

Butt fat vs. Gut fat cells:

Back 25

Gut Fat:
•Large Insulin-
Resistant
Adipocytes
•Adrenergic
Receptors ↑
• Insulin-Mediated
Antilypolysis
•Catecholamine-
Mediated
Lipolysis ↑

-->increase Fatty Acids

Butt Fat:
•Small Insulin-Sensitive
Adipocytes
•Adrenergic Receptors ↓

Front 26

Abdominal vs. reduced obesity

Back 26

Front 27

Plasma Lipids Improve with
Weight Loss Meta-analysis of 70
Clinical Trials

Back 27

Front 28

Relative risks of coronary heart disease for moderate overweight (body mass index [calculated
as weight in kilograms divided by height in meters squared], 25.0-29.9) adjusted for age, sex,
smoking, and physical activity (A) and additionally adjusted for blood pressure and cholesterol
concentrations (B), sorted by descending study size (reflected by the size of the square)

Back 28

Front 29

Relative risks of coronary heart disease for obesity (body mass index [calculated as weight in
kilograms divided by height in meters squared], >=30.0) adjusted for age, sex, smoking, and
physical activity (A) and additionally adjusted for blood pressure and cholesterol concentrations
(B), sorted by descending study size (reflected by the size of the square)

Back 29

Front 30

Dietary Fat Intake

Back 30

• Total fat in the diet to be limited to 25-35% of
total daily calories
• Types of Fat:
– Saturated fat (“bad fat”) – usually solid at room temp
• Increase total cholesterol and LDL; no changes to HDL
– Foods sources:
• Meat, poultry skin
• High-fat dairy products
• Fried foods, chips & snack foods
• Butter
• Baked goods (tropical oils)
• AHA recommends <10% of calories from sat fat

Front 31

Trans Fats

Back 31

• Trans Fats
– Increase total and LDL cholesterol
– Decrease HDL cholesterol
– As little as 1-3% of total calories from trans fat can
impact cholesterol levels
• Produced through process of “hydrogenation”
– Food sources
• Stick margarine
• Crackers and snack foods
• Baked goods
• AHA recommends limiting trans fat (eating as
little as possible)

Front 32

Unsaturated Fats

Back 32

• Unsaturated Fats (usually liquid at room
temp)
• Types of unsaturated fats:
– Monounsaturated (olive oil, canola oil, peanut
oil, nuts, avocado)
– Polyunsaturated fats (sunflower, soybean,
safflower oils)
• AHA recommends 25-35% of calories from
unsaturated fats

Front 33

Omega 3 FAs

Back 33

• Omega-3 Fatty Acids
– Mainly from “fatty fish” (salmon, mackerel,
tuna, but also flax seed oil)
• Omega-3 FA have “anti-inflammatory”
action
• AHA recommends 2-3 servings/week of
fish

Front 34

Carbohydrates and Lipids

Back 34

• Diet high in whole grains and fiber associated
with lower blood lipid levels
• Several studies link high fruit and vegetable
intake with lower total cholesterol and lower
CHD risk (antioxidant content)
• Studies with antioxidant supplements have not
shown the same benefits and may be harmful
(Vitamin E & beta carotene)

Front 35

Protein and Lipid association

Back 35

• Association between high animal protein
intake and increasing blood lipids
• Association between higher protein from
plant sources and lower lipids (Omni Heart
Study).

Front 36

physical activity and lipid association

Back 36

• Physical Inactivity major risk factor for
CHD
• Regular physical activity contributes to
primary and secondary prevention of CHD
LDL
Total cholesterol
HDL Cholesterol
150 – 200 minutes PA per week to prevent a
weight gain of <3% in most adults

Front 37

Physical activity for active weight loss

Back 37

• <150 minutes/week

Front 38

Physical activity for weight loss maintenance

Back 38

• 200-300+ minutes/week (more research is
needed)
• Do more, maintenance is better
Physical activity is best
predictor of weight loss
maintenance!!!!!!!!!

Front 39

Resistance training and weight loss

Back 39

• Research does not support resistance
training as effective for weight loss, with
or without diet restriction.
• May promote gain or maintenance of
lean mass and loss of body fat.
• May improve chronic conditions.
• May increase functional capacity so
client can (and may want to) do more.

Front 40

Common Nutrition/Lifestyle
Recommendations
HTN

Back 40

Hypertension
– Weight Loss*
– Increased physical activity*
– Increased fruit & vegetable
intake*
– Decrease sodium intake

*Associated with decreased
incidence of type 2
diabetes

Front 41

Common Nutrition/Lifestyle
Recommendations
Hyperlipidemia

Back 41

• Hyperlipidemia
– Weight Loss
– Increased physical activity
– Increased fruit and
vegetable intake
– Decreased saturated fat
and trans fat intake*
– Increased
monounsaturated fat and
omega-3 fatty acids

*Associated with decreased
incidence of type 2
diabetes

Front 42

How much physical activity is enough?

Back 42

• Surgeon General: accumulate 30 minutes
of moderate intensity physical activity on
most days of the week
• 10,000 steps/day = 30 minutes of
accumulated physical activity

Front 43

CORONARY ANATOMY

Back 43

• coronary arteries branch from aorta
• epicardial vessels send branches into
myocardium (= endocardial arteries)

Front 44

Which regions of the heart does the RCA supply?

Back 44

rt. ventricle. + posterior. left. vent.

Front 45

Which regions of the heart does the LCA supply?

Back 45

ant. + lateral left. ventricle.

Front 46

What does the coronary circulation deliver?
What does it remove?

Back 46

coronary circulation delivers nutrients
&
removes metabolites/wastes

Front 47

Coronary perfusion occurs primarily during diastole rather than during systole. Why?

Back 47

1. During systole, aortic valves block main coronary artery outflow.

2. As myocardium contracts, endocardial vessels are being compressed-->esp. the ones closest to the blood b/c more muscle is pushing it.

Front 48

Define myocardial ischemia

Back 48

myocardial O2 supply is less than myocardial demand

Front 49

myocardial O2 demands are met by:

Back 49

coronary blood flow.

- myocardium can't extract more O2 from blood
- blood can't carry more O2
- coronary blood flow can increase up to 5X (when there is an increase in demand)

Front 50

What can change myocardial O2 supply?
(coronary blood flow)

Back 50

Aortic Diastolic Pressure

Duration of diastole

coronary vascular bed resistance

Front 51

How does aortic diastolic pressure affect myocardial O2 supply?

Back 51

it is the coronary perfusion pressure

Front 52

How does duration of diastole affect myocardial O2 supply?

Back 52

increase duration of diastole to increase blood flow.

Can increase diastole by decreasing heart rate.

Front 53

How does coronary vascular bed resistance affect myocardial O2 supply?

Back 53

Increase resistance to blood flow which decreases blood flow

Front 54

vasodilation stimuli are:

Back 54

hypoxia, adenosin, decreased pH

Front 55

What affects myocardial O2 demand?

Back 55

wall stress

heart rate

contractility

Front 56

How does wall stress affect myocarcial O2 demand?

Back 56

increase radius of the ventricle, increase myocardial O2 use

The more the ventricle stretches, the more O2 it uses

Front 57

How does Heart rate affect myocarcial O2 demand?

Back 57

increase HR, increase O2

Front 58

How does contractility affect myocarcial O2 demand?

Back 58

increase contractility, increase O2 demand

Front 59

What does exercise do to myocardial O2 demand and how does it do it?

Back 59

Increase O2 demand by sympathetic NS activation

SNS activation increases HR and increases contractility

Front 60

Atherosclerosis Defn

Back 60

Progressive accumulation of oxidized lipoproteins(LDL) and inflammatory cells under endothelium
-->atherosclerotic plaque
-->vessel stenosis (narrowing)

Front 61

Damage of endothelium on Plaque Leads to:

Back 61

plaque rupture -->
thrombus formation-->
occlusion of the blood vessels

Front 62

T/F
Angina is a disease

Back 62

False, angina is a SYMPTOM

chest pain caused by myocardial ischemia

Front 63

Diseases caused by myocardial ischemia that angina is a symptom of:

Back 63

coronary artery disease
ischemic heart disease

Front 64

spectrum of coronary disease:
from least to most severe

Back 64

silent ischemia
stable angina
unstable angina
non-Q wave MI
Q wave MI

Front 65

Define silent ischemia

Back 65

asymptomatic myocardial ischemia

imbalance in O2 supply and demand, but need ECG to diagnose

decrease O2 demand, if ischemia, it can be seen on ECG

-no overt signs to the patient

Front 66

Define stable angina:

Back 66

includes classic and variant angina

Front 67

characteristics of unstable angina:

Back 67

Newly diagnosed angina--> until can define type of angina

change in anginal pattern (trigger for pain has changed)

(variant angina)

Front 68

features of angina:

Back 68

pain caused when coronary blood flow is inadequate to supply O2 required by myocardium
--> myocardial ischemia

Pain caused by:
1. substances released during hypoxia
2. normal metabolites not removed by decreased coronary blood flow

Front 69

Define classic angina

Back 69

(exertional angina, angina of effort)
• associated with atherosclerotic disease of coronary arteries
• occurs when metabolic needs of myocardium exceeds ability of occluded coronary
vessels to deliver adequate blood flow
• precipitated by factors that increase work demands on the heart
e.g., exercise
exposure to cold
emotional stress
• diagnosis = pain relieved by rest or NTG

Front 70

Define Variant angina

Back 70

(vasospastic angina, Printzmetal's angina)
• associated with spasm of coronary arteries (mainly in presence of stenosis)
- hyperactive sympathetic nervous system
- defective Ca2+ handing by coronary vascular smooth muscle
- altered endothelium-derived factors favoring vasoconstriction
- ↑ endothelin or AII
- ↓ PGI2 or nitric oxide
• occurs during rest or with minimal exercise
- frequently nocturnal
- cyclic or regular occurrence

Front 71

Define Unstable Angina

Back 71

(preinfarction angina, crescendo angina)
• associated with obstructive coronary artery disease (+ coronary vasospasm?)
- thrombotic occlusion of coronary artery at site of atherosclerotic plaque
- initiated by platelet aggregation
• pain characterized by changing pattern
• occurs during rest, appears more frequently and lasts longer
• accelerated form of angina

Front 72

What can be done to decrease O2 demand?

Back 72

increase aortic DBP

increase diastole duration (decrease HR)

decrease resistance (dilate vessels)

Front 73

What can be done to increase O2 supply?

Back 73

decrease ventrilcular filling

decrease HR

decrease contractility

Front 74

Therapeutic objective for myocardial ischemia:

Back 74

balance O2 supply and demand
- improve coronary blood flow
- reduce myocardial O2 requirement

Front 75

List the NITRATES

Back 75

nitroglycerin
isosorbide mononitrate
isosorbide dinitrate

Front 76

MOA of nitrates:

Back 76

relax blood vessels by:
release of nitrite → NO formation
→ activation of guanylate cyclase → smooth muscle relaxation (Veins > Arterioles)

Relaxation of epicardial coronary vessels

total coronary blood flow is not increased -> not a generalized vasodilation

coronary flow redistributed from normal to ischemic area via collateral vessels

Front 77

What are the beneficial Effects of dilating veins?

Back 77

increase endocardial blood flow

decrease myocardial O2 consumption

Front 78

What are the beneficial effects of dilating arterioles?

Back 78

coronary vessel dilation

decreased myocardial O2 consumption

Front 79

What disadvantageous effect can occur by dilating veins?

Back 79

Increased contractility, increased HR = NOT GOOD

If decreased BP too much, reflex tachycardia offsets the beneficial effect

Front 80

Side Effects of Nitrates

Back 80

• orthostatic hypotension, dizziness, syncope (b/c vasodilation)
NOTE: If ↓ VR too much → decrease aortic DBP, decrease coronary perfusion pressure

• throbbing headache

• flushing

• ↑ sympathetic discharge-reflex (increase HR and contractility, increase O2 demand)

• tolerance- dilator effect wears off w/ continual use
-8 hr abstinence period each day or lose effectiveness
e.g., explosives factory workers

• dependence
continual exposure to nitrates ⇒ if remove nitrates for 1-2 days
→coronary vasospasm
∴ in chronic users, taper dosing when w/drawing nitrate

Front 81

Indications for Nitrates

Back 81

• used acutely or prophylactically
- sublingual NTG (quick, 1-2 min)
- buccal, oral, transdermal (maintenance) ->TOLERANCE SE, must give 8 hr break

Front 82

Administration of a nitrate to a patient who has taken sildenafil (Viagra®), vardenafil (Cialis®) or
tadalafil (Levitra®) can lead to a precipitous drop in blood pressure. What mechanism
underlies this effect?

Back 82

They act by blocking PDE5

normally:
nitrate->NO->guanylate cyclase->cGMP->vasodilation

cGMP is metabolized by PDE5, and this is blocked by ED drugs, so cGMP levels increase because not being metabolized by PDE5, increase vasodilation, and decrease BP!

Front 83

Calcium Channel Blockers

Back 83

verapamil
diltiazem
amlodipine
nifedipine
nicardipine
felodipine

Front 84

MOA CCBs:

Back 84

Arteriolar selective
• inhibit voltage-dependent calcium channels (see previous section)
→ ↓ Ca2+ influx → smooth muscle relaxation

• vasodilation → ↓ peripheral vascular resistance
→ decrease afterload
→ decrease cardiac work
→ O2 demand (good for classic angina)

• ↓ coronary artery tone → increase coronary perfusion
→ increase blood flow
→ O2 supply
good for variant angina

• ↓ Ca2+ influx in to myocardial cells (verapamil > diltiazem=cardiac suppressive effects)
→ decrease contractility
→ decrease O2 demand

• slows SA node (verapamil, diltiazem)
→ ↓ HR
→ decrease O2 demand

Front 85

Side Effects CCBs:

Back 85

hypotension
dizziness
fatigue
cardiac depression (verapamil and diltiazem + beta blocker b/c decrease AV block and decrease ventricular function) CCB drugs can be contraindicated in heart failure

Front 86

Beta blockers

Back 86

atenolol
metoprolol
propanolal
nadolol
timolol

Front 87

beta blocker MOA

Back 87

β-blockers inhibit effects of catecholamines on heart
exercise, stress → increase sympathetic drive

OVER THE LONG TERM, β-blockers ↓ BP by ↓ PVR → decrease afterload, decrease O2 demand

Front 88

Side Effects beta blockers

Back 88

• ↓ heart rate → ↑ end-diastolic volume → ↑ wall stress
→ increase O2 demand (partially offset beneficial effects) ->combine with nitrate to decrease VR
• withdrawal of chonically-administered β-blocker
→ exacerbation of angina and ventricular dysrhythmias b/c upregulated beta-receptors can now be activated