Coronary Heart Disease

Question 1

When does LV perfusion occur?

Answer 1

during diastole

intracavity pressure & excessive myocyte shortening during systole prevents perfusion

Question 2

Explain the auto-regulation of coronary blood flow.

Answer 2

global coronary flow is auto-regulated so that flow is relatively independent of coronary perfusion pressure
flow=pressure/resistance Ohm’s Law
*flow brings O2 to cells, maintain flow through varying pressures (vary resistance in arterioles to maintain flow)

Question 3

control of coronary vascular resistance

Answer 3

metabolic (O2 demand, byproducts)
autonomic nervous system
humoral
endothelial modulation

Question 4

determinants of MVO2 (myocardial oxygen consumption)

Answer 4

contractility: increased inotrope, increased O2 demand
HR: increased O2 demand
wall tension: Law of Laplace (pressure x radius/2 wall thickness)

Question 5

alpha adrenergic stimulation of coronary vasculature

Answer 5

direct: alpha1 increases epicardial coronary resistance (vasoconstriction); alpha2 increases release of NO (vasodilation)
indirect: increase afterload by peripheral alpha1 stimulation; baroreceptor decrease in HR

Question 6

beta adrenergic stimulation of coronary vasculature

Answer 6

beta 2: decreased epicardial & endocardial vascular resistance

beta1: increased HR, contractility, MVO2
* decrease O2 demand

Question 7

parasympathetic stimulation of coronary vasculature

Answer 7

directly: decrease epicardial & resistance vessel tone
indirectly: decreased HR, ABP, MVO2

Question 8

stable angina

Answer 8

classic; effort-related; relieved w/ rest & medication; fixed lesion; regular pattern

Question 9

variant angina

Answer 9

Prinzmetal; transient vasospasm while resting; often severe crushing pain; often occurs in cycles

Question 10

unstable angina

Answer 10

acute coronary syndrome; MI; emergent; severe atherosclerosis & stenosis; release of vasoconstrictor substances

Question 11

microvascular angina

Answer 11

lasts longer; not acute

Question 12

pharmacological targets for decreasing CVR

Answer 12

• -increasing cGMP to prevent interaction of myosin w/ actin (nitrates)
• -decrease intracellular Ca+2 (Ca+2 channel blockers)
• -inhibit platelet aggregation (Asp, etc)
• -stabilize/prevent plaque (statins)
• -anticoagulants (thrombin inhibitors)

Question 13

pharmacological targets for reducing HR & contractility

Answer 13

beta blockers: block SNS

cardio-selective Ca+2 channel blockers: decrease intracellular cardiac myocyte calcium

Question 14

pharmacological targets for decreasing wall stress (decrease preload/afterload, increase wall thickness)

Answer 14

venodilation: nitrates to increase cGMP
vasodilation: nitrates increase cGMP, vasoselective Ca+2 channel blockers, RAAS blockers to decrease AII
decreased hypertrophy & vascular remodeling: RAAS blockers

Question 15

mechanism of action of nitrovasodilators

Answer 15

reduce O2 demand: venodilator decreases preload, arterial vasodilator decreases afterload, reduce wall stress & MVO2
increase O2 supply: dilate conduit arteries at stenosis, increase collateral flow, increase subendocardial flow, decrease plt activation

Question 16

What is tachyphylaxis?

Answer 16

the more you give a med, the more it doesn’t work ex: nitrates

Question 17

Why don’t dihydropyridines affect veins?

Answer 17

relax vascular smooth muscle of arteries (little smooth muscle in veins)

Question 18

How do cardioselective Ca+2 channel blockers decrease contractility?

Answer 18

decrease sinus node pacemaker rate and AV node conduction velocity

Question 19

Why is nicardipine used to prevent vasospasm?

Answer 19

Ca+2 channel blocker; increase cerebral O2 supply by dilating cerebral arteries to increase coronary blood flow

Question 20

Ca+2 channel blockers vs nitrates

Answer 20

epicardial vs subendocardial activity

Question 21

Why should you avoid Ca channel blockers in HF?

Answer 21

d/t negative inotropic effect (esp verapamil)

Question 22

Beta2 receptor antagonists may increase vasospasms. Therefore they should not be used in pts w/…

Answer 22

SAH

Prinzmetal’s angina

Question 23

mechanism of action of ranolazine

Answer 23

inhibits late Na current to redue Na and Ca overload in ischemic myocytes; shift ATP production from fatty acid oxidation to glycolysis

Question 24

mechanism of action of P2Y12 receptor antagonist

Answer 24

clopidogrel, prasugrel

block ADP-mediated activation of glycoprotein GPIIb/IIIa

Question 25

chronic tx of unstable angina

Answer 25

• -prevent plt activation & aggregation (Asp, P2Y12 inhibitor, glycoprotein IIb/IIIa blocker
• -limit thrombus formation (heparin, thrombin inhibitor)
• -prevent vasoconstriction (nitrates, Ca channel blocker)
• -inhibit RAAS
• -reduce MVO2 & prevent vasoconstriction (nitrates, ACEIs, ARBs, Ca channel blockers)
• -stabilize atherosclerotic plaque (statins, antiplt)

Question 26

tx acute MI

Answer 26

fibrinolytic therapy dependent on duration of ischemia; coronary intervention (angio, CABG)

Question 27

tx stable angina

Answer 27

acute: sublingual nitro
chronic: beta receptor antagonist, low dose Asp, Ca channel blockers, long-acting nitrates, ACDIs & ARBs, statins

Question 28

What is syndrome X and how is it treated?

Answer 28

angina or angina-like discomfort w/ exercise, ST-segment depression or other signs of ischemia; caused by normal coronary arteries w/ microvascular dysfunction; tx w/ beta blockers, Ca channel blockers, nitrates, ACEIs, statins

Question 29

tx of Printzmetal angina

Answer 29

nitrates, Ca channel blockers

*no beta blockers b/c they may make vasospasm worse