Coronary Artery Disease

Question 1

What generates symptoms in coronary artery disease?

Answer 1

• mismatch between oxygen supply and demand

Question 2

Name factors that favor vasodilation

Answer 2

• shear stress, nitrates (NO), β2, adenosine, EDHF

Question 3

Name factors that favor vasoconstriction

Answer 3

• α1, 5-HT, TXA2, angiotensin II, endothelin

Question 4

What are two drug strategies used in the treatment of angina?

Answer 4

• increase oxygen delivery by decreasing vasospasm or dilating arteries
• decrease oxygen requirement by decreasing TPR, CO, or both

Question 5

What is the most important contributor to the electrophysiologic changes seen in ischemia?

Answer 5

elevated extracellular potassium (extracellular levels of lactate, phosphate, and fatty acids also rise)

Question 6

Describe the systolic and diastolic injury currents seen between ischemic cells and normal cells

Answer 6

• **Systolic: during phase 2 and 3, the shortening of the AP causes ischemic cells to be more negative, so current flows from normal cells to ischemic ones
• Diastolic: during phase 4, ischemic cells are less negative so current flows from ischemic cells to normal ones

Question 7

Ticlopidine is an antiplatelet agent. How does it work and what are the side effects?

Answer 7

• inhibits platelet aggregation induced by adenosine diphosphate and reduces blood viscosity by reducing plasma fibrinogen and increasing red cell deformability
• SE: neutropenia, rarely TTP

Question 8

Which drug irreversibly inhibits binding of adenosine by binding to adenosine receptors and blocking the activation of glycoprotein IIb/IIIa complex?

Answer 8

• clopidogrel
• greater antithrombotic effects than ticlopidine
• used with stent placement to prevent aggregation

Question 9

How does prasugrel work and what kind of patients is it used in?

Answer 9

• irreversibly binds to P2Y receptor (antiplatelet)
• associated with an increased risk of bleeding, so limited to use in patients younger than 75, greater than 60kg, and no history of stroke or TIA

Question 10

This drug is an antiplatelet, reversibly blocks ADP receptors, doesn’t require hepatic activation, has a fast onset of action and elimination, and has been associated with higher risks of bleeding events

Answer 10

• ticagrelor

- don’t supplement with aspirin over 100mg!

Question 11

These two drugs are used primarily for claudication that is associated with peripheral vascular disease. They can’t really be used for angina, mostly because of their vasodilatory cardiac concerns. What are they and how does each work?

Answer 11

• dipyridamole and cilostazol
• both inhibit cellular phosphodiesterase and lead to increased levels of platelet cAMP, which inhibits platelet aggregation

Question 12

What are the effects of angiotensin II?

Answer 12

• vasoconstriction of arterioles
• stimulates release of aldosterone
• stimulates release of ADH

Question 13

ACE inhibitors are shown to do what in the setting of cardiac disease (and this cannot be attributed to blood pressure reduction alone!)?

Answer 13

• reduces incidence of death, MI, and stroke in subjects with and without heart failure
• shows positive effects on remodeling of heart

Question 14

Which is the shortest acting ACE inhibitor? Name some others, while you’re at it

Answer 14

• shortest acting: captopril

- enalapril, lisinopril, ramipril, quinapril, fosinopril

Question 15

What anginal condition are β blockers contraindicated in?

Answer 15

• vasospastic (Prinzmetal’s) angina
• in angina of exertion, β blockers work by decreasing the oxygen demand
• most used for CAD are β1 selective

Question 16

What are contraindications to use of a β blocker?

Answer 16

• severe bradycardia
• high degree AV block
• sick sinus syndrome
• unstable acute LV failure
• asthma
• severe depression
• peripheral vascular disease

Question 17

How do nitrates work?

Answer 17

• travel into smooth muscle cell, reduced to NO which activates guanylyl cyclase to form cGMP
• cGMP decreases intracellular Ca, which results in smooth muscle relaxation and vasodilation
• biggest effect is on venous dilation (decreases preload), but also dilates epicardial coronary vessels

Question 18

What kind of angina do nitrates work on? What are some side effects?

Answer 18

• both stable and unstable angina, usually taken at onset of pain
• SE: headaches, hypotension, Bezold-Jarisch reflex/bradycardia, and development of tolerance with chronic use
• tolerance due to depletion of tissue sulfhydryl groups - must incorporate nitrate free periods into dosing

Question 19

Patient presents to the ER with severe anginal pain. What are some pre-existing conditions you want to make sure he doesn’t have before you give him some nitroglycerin?

Answer 19

• hypertrophic cardiomyopathy
• severe aortic stenosis
• already hypotensive
• current use of PDE inhibitors for his ED

Question 20

How do calcium channel blockers work as vasodilators?

Answer 20

• reduce flux of calcium across membrane , which relaxes muscle cells
• also works as a negative inotrope

Question 21

What calcium channel blockers are important in the treatment of unstable angina?

Answer 21

• the vasoselective dihydropyridines (amlopdipine, felodipine, isradipine)