Angina Lecture 1 and 2

Question 1

Cardiac muscle is highly

Answer 1

efficient extracting O2 even at rest (increased O2 delivery to myocardial tissue is dependent on CORONARY ARTERY vasodilation): think shear stress to dilate vessels or nitrates

Question 2

What contributes to myocardial supply and demand?

Answer 2

Supply: vascular resistance and coronary blood flow (O2 carrying capacity);
Demand: (HR, contractility, systolic wall tension)

Question 3

Angina usually occurs in patients with

Answer 3

CAD involving at least one epicardial artery; also valvular heart disease (increase strength of contractility and increase O2 demand in myocardium), hypertrophic cardiomyopathy, uncontrolled HTN (heart overtaxed even at rest)

Question 4

As myocardial O2 delivery falls:

Answer 4

1. anaerobic glycolysis inadequate to maintain cellular functions
2. ATP and creatine phosphate levels fall
3. IC and EC acidosis develops
4. EC levels of K, lactate, phosphate, and FA levels rise;

Question 5

elevated EC ____ is the most important contributor to

Answer 5

K; electrophysiologic changes of ischemia (increased K leaks outward)

Question 6

Gradients exist between _____ in ischemia:

Answer 6

ischemic and normal cells, and seen on EKG;
in phase 4, IC positive current goes from less neg to ischemic cells to more negative normal cells (diastolic current); FOCUS MORE ON systolic current of injury with AP of ischemic cells being more negative than normal cells during phase 2 and 3 with IC positive current going from NORMAL to ISCHEMIC cells

Question 7

How to diagnose ischemia?

Answer 7

Noninvasive:

1. stress testing (treadmill with 6-12 min of exercise if they can; try to hit 85% max HR, or 220-age)
2. can do test with ECG alone if normal baseline ECG (positive with at least 1 mm of horizontal or downsloping ST depression)
3. if baseline ECG is ABNORMAL, do imaging like echo to look at wall motion abnormalities or perfusion imaging
4. If patient CAN’T EXERCISE, use pharmacologic stress with dobutamine (sympathomimetic drug with beta-1 receptors to increase HR and contractility; or adenosine or dipyridamole as vasodilators, but stenotic arteries can’t respond to vasodilation stimulus and leads to coronary steal)

Question 8

Diagnosis of CAD:

Answer 8

1. Stress testing reveals ONLY presence of hemodynamic significant lesions, but WON’T directly image the vessels
2. For direct imaging of coronaries, think coronary angiogram (minority: CT angiogram)
3. Maybe consider electron beam CT scanning: ID Ca in the coronaries, and very useful in predicting absence of CAD

Question 9

Medical management of CAD:

Answer 9

1. ID and treat risk factors for cardiovascular disease (lipid abnormalities for cholesterol, smoking, diabetes, HTN);

Aim is to FIRST prevent MI and death to increase QUANTITY of life; however, want to reduce symptoms of angina and occurrence of ischemia or QUALITY of life;
use strategy that has greater chance of PREVENTING DEATH

Question 10

Aspirin (Unit IV)

Answer 10

Class: NSAID
Mech: Irreversible inhibition of platelet COX (need COX for prostaglandin and thromboxane synthesis; no Thr A2, no platelet aggregation)
Thera: Reduction in adverse events (MI, CVA, death); for those w/stable angina, unstable angina, acute MI, prophylaxis
Important SE’s: bleeding complications with GI bleeds, bruises, anemia with increased aspirin dose
Misc: Low-doses; if you’re allergic, you’ll get asthma

Question 11

Ticlopidine (Ticlid)

Answer 11

Class: Thienopyridine derivitive
Mech: Inhibits platelet aggregation by ADP; reduces blood viscosity by decreasing plasma fibrinogen and increasing RBC deformability
Thera: Aspirin alternative
Important SE’s: Neutropenia and, rarely, TTP
Misc: Not really used anymore (no decrease in adverse events in those w/ stable angina)

Question 12

Clopidogrel (Plavix)

Answer 12

Class: Thienopyridine derivitive
Mech: Selectively and irreversibly inhibits ADP binding to P2Y12 (blocks ADP-dependent activation of glycoprotein IIb/IIIa complex)
Thera: Great antithrombotic (compared to aspirin or ticlopidine)
Important SE’s: Bleeding (more so than e.g. aspirin)
Misc: No surgical or dental procedures if patient taking this

Question 13

Prasugrel (Effient)

Answer 13

Class: Thienopyridine derivitive
Mech: Irreversibly binds P2Y12 receptor (G protein-coupled chemoreceptor for ADP)
Thera: Reduce thrombotic events in those w/percutaneous coronary intervention (e.g., stent), like ACS
Important SE’s: Massive bleeding risk
Misc: more potent antiplatelet agent compared to e.g. aspirin and clopidogrel in reducing rates of death, CVA, MI; limit this to
1. Patients less than 75
2. Weight more than 60 kg
3. No history of stroke or TIA

Question 14

Ticagrelor (Brilinta)

Answer 14

Class: similar in structure to adenosine
Mech: blocks ADP receptors, but is a reversible blockade (different binding site than ADP)
Thera: ACS?; better mortality results compared to clopidogrel
Important SE’s: non-lethal bleeding
Misc: no hepatic activation and so faster onset of action; eliminated faster so more dosing required and issues with patient compliance

Question 15

Dipyradimole (Persantine)

Answer 15

Class: Pyrimido-pyrimidine derivitive
Mech: Increases platelet intracellular cAMP (inhibits phosphodiesterase 5, activates adenylate cyclase, inhibits uptake of adenosine from vascular endothelium and RBCs)
Thera: Decrease peripheral vascular disease (as an adjunct); stress test of heart
Important SE’s: Vasodilation of coronary arteries can enhance exercise-induced ischemia (because it elevates extracellular adenosine levels)

Question 16

Cilostazol (Pletal)

Answer 16

1. quinolinone derivative that inhibits cellular phosphodiesterase
2. causes increase in cAMP levels which results in inhibition of platelet aggregation
3. Causes vasodilation: cause of increased mortality and morbidity in HEART FAILURE patients

Question 17

ACE inhibitors

Answer 17

Class: ACE inhibitor
Mech: Blocks endothelial ACE from converting angiotensin I to angiotensin II (potent vasoconstrictor); as a side effect, also prevents breakdown of bradykinin (potent vasodilator) since ACE is known as Kininase II
Thera: Often used as an add-on antihypertensive for anyone with chronic kidney disease/proteinuria, CHF, left ventricular hypertrophy, or post-MI (prevents left ventricular remodeling); reduces incidence of future CAD events, may reduce risk of diabetes
Important SE’s: Dry cough (most common), angioedema (can be fatal), decreased renal function, hypotension (bradykinin can cause cough and angioedema, latter around mouth, mucosa, tongue, skin, etc.)
Misc: Short-acting; contraindicated in pregnancy, renal artery stenosis, hyperkalemia, and prior angioedema (no ARB allowed, either); caution in renal failure

Question 18

Metoprolol, propranolol, bisoprolol (beta-1 selective)

Answer 18

Class: β-blocker
Mech: Decrease contractility, HR (reduced myocardial O2 demand); class II antiarrhythmics (inhibit sympathetic influence on cardiac electrical activity like SA node automaticity, conduction velocity, aberrant pacemaker activity; increase AP duration and effective refractory period in AV node); block epi and NE binding to beta-adrenoreceptors
Thera: Prevent MIs, prevent sudden cardiac death, increase survival post-MI (if patients suddenly stop, really bad!)
Important SE’s: Fatigue, decreased exercise tolerance, worsening claudication, impotence (so men don’t take), insomnia and lethargy
Misc: Contraindicated in severe bradycardia, high degree AV block, sick sinus syndrome, unstable LV failure; relative contraindication is asthma and bronchospastic disease, severe depression, peripheral vascular disease

Question 19

Nitrates

Answer 19

Class: Vasodilator
Mech: Endothelium independent vasodilator with nitrates interacting with enzymes and IC sulfhydryl groups that reduce nitrate groups to NO to activate smooth muscle soluble GC to form cGMP, which inhibits Ca entry into cell to get smooth muscle relaxation; dilates large epidcardial coronary arteries and collateral vessels to relieve coronary vasospasm and venous dilation predeominates; endothelial effects (inhibits platelet aggregation, inhibits leukocyte-endothelial interactions (anti-inflammatory));
Thera: For acute episodes; long-acting formulations are for those already on other drugs and still can’t control angina
Important SE’s: Tolerance w/chronic use due to peroxynitriate production (need nitrate free periods of 8-12 hours), headaches, hypotension, activation of Bezold-Jarisch reflex (causes bradycardia)
Other SE’s: Increase preload?
Misc: Contraindicated in hypertrophic cardiomyopathy, severe aortic stenosis, significant hypotension, use of phosphodiesterase inhibitors

Question 20

Nefedipine (Procardia)

Answer 20

Class: Calcium channel blockers (dihydropyridines, 1st generation)
Mech: Interact with L-type voltage gated plasma membrane Ca channel –> decreased calcium entry into vascular smooth muscle cell, preventing contraction; causes DILATION of epicardial coronary arteries, arteriolar resistance arteries; less heart-specific activity, but more than 1st generation
Thera: Hypertension, Raynauds, angina (3rd choice drug)
Important SE’s: Leg edema, heart failure, AV nodal blockade, reflex tachycardia (lipophilic agents gain entry to brain and depress vasomotor center, rapidly dropping BP; this causes more reflex sympathetic activation (leading to adverse CV effects); long-acting agents are less lipophilic, and will cause less sympathetic activation and initial fall in BP)
Other SE’s: Constipation (most common), headache, flushing
Misc: Contraindicated in overt decompensated heart failure, bradycardia, sinus node dysfunction, high-degree AV block;
some negative inotropic effect

Question 21

Amlodipine (Norvasc): difference with Nefedipine?

Answer 21

Less leg edema!!

Question 22

Felodipine (Plendil), Isradipine (Dynacirc): difference with amlodipine?

Answer 22

Not indicated for ANGINA!!

Question 23

Verapamil (Calan)

Answer 23

Class: Calcium channel blockers (nondihydropyridines, phenylalkamine type)
Mech: Interact with L-type voltage gated plasma membrane Ca channel –> decreased calcium entry into vascular smooth muscle cell, preventing contraction; causes decreased contractility, firing rate of aberrant pacemaker sites, and conduction velocity; prolongs repolarization in SA node and AV node (–> decreases HR); less systemic vasodilation
Thera: Hypertension, anti-anginal (chronotropic effects –> decreased myocardial oxygen demand), SVT (class IV anti-arrhythymic)
Important SE’s: Leg edema, bradycardia, AV nodal blockade, hypotension, worsening heart failure
Other SE’s: Constipation (most common), headache, flushing
Misc: Contraindicated in overt decompensated heart failure, bradycardia, sinus node dysfunction, high-degree AV block

Question 24

Diltiazem (Cardizem): difference from verapamil?

Answer 24

Class: Calcium channel blockers (nondihydropyridines, benzothiazepine type);
intermediate b/w verapamil and dihydropyridines!!!