IHD Phys/Pharm

Question 1

what is the primary mechanism by which O2 delivery to myocardium is matched with demand?

Answer 1

autoregulation of arterioles

Question 2

what does myocardial oxygen supply depend on?

Answer 2

oxygen content of blood: usually constant

coronary blood flow: increased demand met by increased coronary flow

Question 3

coronary flow (Q) equation?

Answer 3

Q is directly proportional to perfusion pressure (P) and inversely related to coronary vascular resistance (R)

Question 4

what does perfusion pressure depend on?

Answer 4

diastolic pressure, not systolic pressure. and coronary vascular resistance, which is dynamically modulated (by external compression and intrinsic regulation by metabolites, endothelial factors and neural innervation)

Question 5

when is flow low? rapid? where does it fluctuate least?

Answer 5

low during systole d/t muscle compression. rapid during diastole. less fluctuation in R ventricular myocardium

Question 6

how is flow matched with need?

Answer 6

by autoregulation: metabolic factors like adenosine, lactate, pH

Question 7

what effect does the sympathetic nervous system have?

Answer 7

a1 receptors = constriction
B2 receptors = dilation (minor)
but over-ridden by metabolic regulation

Question 8

how is blood flow distributed in myocardium?

Answer 8

by epicardial coronary arteries: smaller arteries supply inner layers, subendocardial plexus. flow limited more during systole d/t compressive forces

Question 9

factors determining myocardial O2 demand?

Answer 9

contractile state, HR, wall stress. always high but o2 requirement increases w increased HR and contractility

Question 10

wall stress determinants?

Answer 10

(P*r)/2h. approximated by Laplace’s law. wall stress (and therefore O2 demand) increases w increased ventricular volume or pressure. thicker wall = more stress.

Question 11

what is coronary flow reserve?

Answer 11

when demand for o2 increases, arterioles dilate allowing for increased flow. coronary flow reserve is max increase in blood flow achievable above normal resting flow

Question 12

impact of fixed vessel narrowing on coronary flow reserve? 70% vs 90%?

Answer 12

obstruction increases resistance, reduces distal perfusion pressure, limits flow reserve. 70% obs = probs w exercise. 90% = probs at rest.

Question 13

why is exertion a problem w limiting stenosis?

Answer 13

reduced perfusion pressure, elevated LV end-diastolic pressure w exertion impedes subendocardial flow (less of a P gradient), and increased HR decreases time during diastole so less flow to subendocardium then

Question 14

what ECG abnormality is seen during transient subendocardial ischemia?

Answer 14

ST segment depression (also T wave inversion)

Question 15

effect of collateral BVs?

Answer 15

pre-exist but normally closed. w occlusion, open. helps to supply flow to ischemic regions. important in limiting area of ischemia during acute vessel closure.

Question 16

what is the impact of endothelial dysfunction?

Answer 16

ischemia d/t inappropriate vasoconstriction (impaired release of endothelial vasodilators) and loss of normal anti-thrombotic properties like platelet aggregation.
contributes to reduced o2 supply in chronic CAD too.

Question 17

consequences of ischemia?

Answer 17

inadequate oxygenation (decreased ATP impairs ctxn/relaxation and increased diastolic P can cause pulmonary congestion/dyspnea)
local accumulation of metabolic waste products that can activate pain receptors and precipitate arrhythmias. ultimate fate depends on severity and duration of ischemia.

Question 18

what is stable angina?

Answer 18

predictable transient chest discomfort w/ exertion or emotional stress d/t fixed obstructive plaque in one or more arteries. reduced flow may be fine at rest but not w increased o2 demand. inappropriate vasoconstriction.

Question 19

what is unstable angina?

Answer 19

sudden increase in ischemic episodes, occurring with lesser degrees of exertion and even at rest. ACS. can result from rupture of unstable plaque w subsequent platelet aggregation and thrombosis

Question 20

what is variant angina?

Answer 20

focal coronary artery spasm (Prinzmetal’s angina) in which intense vasospasm reduces coronary O2 supply causing angina

Question 21

what is silent ischemia?

Answer 21

episodes of cardiac ischemia that sometimes occur in the absence of discomfort or pain

Question 22

what is syndrome X?

Answer 22

patients who have signs of angina but no evidence of significant atherosclerotic stenoses

Question 23

what are the clinical features of chronic stable angina?

Answer 23

pressure, discomfort, tightness in chest (w exercise). sometimes sympathetic and parasympathetic activation (tachycardia, sweating). caused by increased O2 demand, relieved by stopping activity.

Question 24

chronic stable angina diagnostic studies and results?

Answer 24

EKG: ST segment depression, T wave inversion (during ischemia), sometimes ST elevation seen if severe transmural ischemia.
Stress test: treadmill, monitor to assess. or give dobutamine, adenosine.
Coronary angiograph

Question 25

general principle of anti-angina therapy?

Answer 25

decrease O2 demand, increase O2 supply

Question 26

how can you decrease O2 demand?

Answer 26

decrease HR, decrease contractility, decrease wall tension (reduce afterload, decrease preload)

Question 27

how can you increase O2 supply?

Answer 27

improve blood flow to subendocardium, increase collateral blood flow, stop coronary spasm, dilate eccentric stenosis

Question 28

therapy for acute episodes of chronic stable angina?

Answer 28

stop physical activity, fast-acting nitrates

Question 29

prevention of episodes of chronic stable angina?

Answer 29

decrease cardiac workload and increase myocardial perfusion with:
long-acting nitrates
B adrenergic receptor blockers
calcium channel blockers

Question 30

nitrates’ effect is primarily on which vessels?

Answer 30

venous blood vessels

Question 31

mechanism of nitrates?

Answer 31

free nitrate converted to NO. NO activates GC, increasing cGMP. that activates PKG, which phosphorylates various targets leading to decreased Ca and dephosphorylation of myosin

Question 32

what effect do nitrates have on preload? why? results?

Answer 32

decrease preload: increase venous capacitance. results in reduced diastolic wall tension and O2 demand. also increases subendocardial blood flow.

Question 33

what effect do nitrates have on afterload? why?

Answer 33

small reduction in systemic arterial BP (afterload). slight reflex tachycardia.

Question 34

what effect on coronary arteries?

Answer 34

coronary dilation: good if due to vasospasm

Question 35

nitrates pharmacokinetics?

Answer 35

low bioavilibility d/t 1st pass metabolism. isosorbide dinitrate metabolized to mononitrate (metabolically active). mononitrate is not metabolized.

Question 36

how are nitrates given acutely? onset/duration of action?

Answer 36

sublingual tablets or spray. fast onset, short duration

Question 37

how are nitrates given chronically?

Answer 37

dinitrate form available in controlled release forms. nitroglycerin as controlled release tabs/caps. or patch & ointment.

Question 38

nitrates tolerance?

Answer 38

develops quickly (hours), but goes away quickly. limits effectiveness of slow-release forms of nitrates w/ maintenance therapy.

Question 39

adverse effects of nitrates?

Answer 39

d/t CV actions: headache, hypotension, reflex tachycardia, flushing

Question 40

how do B blockers exert anti-anginal effect? not useful with what type?

Answer 40

reduce O2 demand: decrease ventricular contraction and HR. not useful if due exclusively to vasospasm

Question 41

how do beta blockers decrease O2 demand?

Answer 41

decrease HR, decrease contractility, decrease BP (afterload)

Question 42

what effect do beta blockers have on preload?

Answer 42

increase preload, causes increase in wall tension

Question 43

B blockers CI?

Answer 43

obstructive airway dz, not w acutely decompensated heart failure, ppl w marked bradycardia or heart block types

Question 44

calcium channel blockers-mechanisms and two types

Answer 44

• Antagonize voltage-gated L-type calcium channels

- dihydropyridines and non-dihydropyridines

Question 45

CCBs-dihydropyridines

Answer 45

Dihydropyridines
• Potent vasodilators
• Relieve ischemia by:
– Decreasing oxygen demand (vasodilation primarily decreases afterload and thereby reduces wall stress)
– Increasing oxygen supply by coronary vasodilation
• Potent agents for the relief of vasospasm
• Nifedipine, amlodipine

Question 46

CCBs-non-dihydropyridines

Answer 46

Non-Dihydropyridines
• Vasodilators (but less potent than dihydropyridines)
• Relieve ischemia primarily by:
– Decreasing oxygen demand by reducing the force of contraction and heart rate
• Verapamil, diltiazem

Question 47

adverse effects of CCBs

Answer 47

• Headache, flushing
• Decrease contractility (V, D)
• Bradycardia (V, D)
• Edema (especially N, D)
• Constipation (especially V)

Question 48

anti-anginal drugs can be used alone or in combination…what are potential benefits/risks?

Answer 48

• Potential benefits of combining a nitrate with a b blocker:
– b blockers prevent the potential reflex increase in heart rate and
contractility produced by nitrates
– Nitrates prevent the potential increase in wall tension produced
by b blockers
• Care should be taken in combining a b blocker with a nondihydropyridine calcium channel blocker
– Additive negative inotropic effect can cause excessive cardiodepression

Question 49

Ranolazine

Answer 49

• Fourth type of anti-ischemic therapy (recently available)
• Decreases frequency of anginal episodes and increases exercise capacity
• Does not work by affecting heart rate of vasodilation
• Believed to inhibit the late sodium current (INa+) in cardiac myocytes

Question 50

Medical Therapy to Prevent Acute Cardiac Events

Answer 50

• Antiplatelet therapy (Pfister)
– Platelet aggregation and thrombosis are key elements in the pathophysiology of acute MI and unstable angina
– Antiplatelet therapy reduces the risk of these acute coronary syndromes
• Aspirin – used indefinitely in patients with known CAD
• Use ADP P2Y12 receptor blockers (i.e., clopidogrel) if aspirin is contraindicated

• Lipid-regulating therapy
– Particularly HMG-CoA reductase inhibitors (statins)

Question 51

Revascularization

Answer 51

• Pursued if:
– Inadequate response to medical therapy
– Unacceptable side effects of medications
– If patient is found to have high-risk disease for which revascularization is known to improve survival
• Revascularization achieved by:
– Percutaneouscoronaryintervention(PCI)
– Coronary artery bypass graft surgery (CABG)

Question 52

PCI

Answer 52

• Includes percutaneous
transluminal coronary
angioplasty (PTCA)
– Balloon-tipped catheter inserted through a peripheral artery (usually femoral) and maneuvered into the stenotic segment of a coronary vessel
– ~1/3 of patients develop recurrent symptoms in 6 months due to restenosis of the dilated artery
• Coronary stents including drug-eluting stents reduce the rate of restenosis

Question 53

CABG

Answer 53

• Involves grafting portions of a patient’s native blood vessel to bypass an obstructed artery
– Use of native veins (i.e., saphenous)
– Arterial grafts (i.e., internal mammary artery)