Cv 10: Ischemic Heart Disease Drugs

Front 1

What is the primary symptom of Ischemic Heart Disease?

Back 1

Angina Pectoris

Front 2

What causes Angina Pectoris?

Back 2

- Accumulation of metabolites resulting from ischemia
- Pain perception is d/t release of mediators from ischemic muscle that activate sensory nerves
- Most commonly d/t flow-limiting stenoses (typical stable) and can be a combination of both forms

Front 3

What is the description of Angina Pectoris?

Back 3

- Pressure, heaviness, tightness, squeezing, burning, choking sensation
- Pain can radiate to L shoulder, flexor region of L arm, jaw, or abdomen
- Women have atypical pain

Front 4

What are the symptoms of Angina Pectoris besides the chest pain?

Back 4

- Nausea
- Dyspnea (labored breathing)
- Diaphoresis (sweating)

Front 5

What are the types of Angina Pectoris?

Back 5

- Typical / Stable
- Variant / Vasospastic
- Unstable

Front 6

How big of an obstruction is seen in Typical / Stable Angina? When does chest pain occur? Other names?

Back 6

- Continuous obstruction >70% of large coronary vessels
- Chest pain occurs with increased oxygen demand (exertion, emotional stress)
- AKA termed effort, classic, or secondary angina

Front 7

What is the cause of Variant / Vasospastic Angina? Other names?

Back 7

- Transient spasm of localized portions of large coronary vessels usually near atheromas
- O2 supply is reduced d/t reversible coronary spasm
- AKA vasospastic, primary, atypical, Prinzmetal's angina

Front 8

What are the goals of anti-Anginal therapy?

Back 8

- Reduce frequency of angina episodes and improve exercise tolerance
- Improve oxygen supply-demand balance

Front 9

What drugs are used for anti-Anginal therapy?

Back 9

- Nitrates
- β-blockers
- Ca2+ Channel blockers

Front 10

What factors determine oxygen demand?

Back 10

- Contractile state
- Heart rate
- Wall tension

Front 11

How do you determine what is the wall tension?

Back 11

LaPlace's Law
Wall Tension = (radius * pressure) / (2 * wall thickness)

Front 12

What increases oxygen requirements?

Back 12

- ↑ HR
- ↑ Contractility
- ↑ Arterial Pressure
- ↑ Ventricular Volume

Front 13

How much of the oxygen supply is extracted at rest?

Back 13

75%

Front 14

What determines the Oxygen Supply?

Back 14

- AV oxygen difference
- Coronary blood flow

Front 15

How do you meet an increased demand for oxygen?

Back 15

Increased coronary flow

Front 16

What is the resting coronary flow? What amount of the C.O.? How is it affected by exercise?

Back 16

- ~225 mL/min
- 4-5% of C.O.
- Can ↑ 4-7x during exercise

Front 17

What are the characteristics of coronary blood flow?

Back 17

- Phasic
- Low during systole (d/t compression)
- Rapid flow during diastole
- Less fluctuation in RV myocardium

Front 18

How does the flow of blood through the coronary arteries match the need?

Back 18

- Local release of vasodilators: adenosone and NO
- Actions of metabolic sensors in vascular smooth muscle (ATP-sensitive K+ channels)

Front 19

What is the function of ATP-sensitive K+ channels?

Back 19

- Sense low ATP in vascular smooth muscle (means there is low O2)
- Opens K+ channels to allow vasodilation of vascular smooth muscle (so that more O2 can get to the site)

Front 20

How is coronary blood flow regulated by the ANS?

Back 20

- α1 receptors - constriction
- β2 receptors - dilation (minor)
- Over-ridden by metabolic regulation (ATP-sensitive K+ channels)

Front 21

How does blood get to the myocardium?

Back 21

- Blood supplied by coronary arteries on epicardium
- Smaller arteries are derived from epicardial arteries and dive into myocardium to supply inner layers of muscle and feed subendocardial plexus
- Flow is limited to a greater extent during systole

Front 22

Which part of the heart's blood flow is most affected by systole / compressive forces? How does it compensate?

Back 22

- Flow to endocardium is limited to a greater extent during systole because compressive forces are greater in subendocardium
- However, preferential dilation of endocardial vessels causes a large increase in flow during diastole

Front 23

What is coronary flow reserve?

Back 23

- When demand for O2 ↑, arterioles dilate to allow for ↑flow (metabolic regulation)
- The maximal ↑ in blood flow achievable above normal resting flow = Coronary Flow Reserve

Front 24

What can limit the coronary flow reserve?

Back 24

- Plaque obstruction of epicardial coronary arteries
- ↑ Resistance
- ↓ Distal perfusion pressure
- Limits flow reserve

Front 25

What happens to the coronary flow reserve when there is a >70% obstruction of the coronary arteries?

Back 25

Distal perfusion pressure is not sufficient to sustain increased flow required during periods of INCREASED DEMAND

Front 26

What happens to the coronary flow reserve when there is a >90% obstruction of the coronary arteries?

Back 26

Distal perfusion pressure is not sufficient to sustain normal RESTING blood flow

Front 27

Why does subendocardial ischemia develop with exertion when there is a limiting stenosis?

Back 27

- Reduced coronary flow reserve
- Elevated end-diastolic pressure impedes subendocardial flow
- Increased HR decreases time during diastole when subendocardium receives blood flow

Front 28

What are the ECG changes with subendocardial ischemia?

Back 28

- ST segment depression
- T-wave inversion

Front 29

What is the function of collateral blood vessels?

Back 29

- Interconnect epicardial coronary arteries
- Helps supply blood flow to ischemic regions
- Limits areas of ischemia during acute vessel closure

Front 30

How do the collateral blood vessels become utilized?

Back 30

- Pre-exist to some extent but are normally closed and non-functional because no pressure gradient exists to drive flow
- With occlusion, distal pressure drops and vessels open

Front 31

What factors decrease O2 demand / may be mechanisms of anti-angina therapy?

Back 31

- ↓ HR
- ↓ Contractility
- ↓ Wall Tension
- ↓ Afterload (systolic wall tension)
- ↓ Preload (diastolic wall tension)

Front 32

What factors increase O2 supply / may be mechanisms of anti-angina therapy?

Back 32

- Improved blood flow to subendocardium
- ↑ collateral blood flow
- Stop coronary spasm
- Dilate eccentric stenosis

Front 33

What is the goal of drugs for acute anginal episodes? Which drugs are used for this?

Back 33

- Goal is rapid relief of pain
- Use: fast-acting nitrates

Front 34

What is the goal of drugs for chronic anginal episodes? Which drugs are used for this?

Back 34

- Goal is to reduce occurrence
- Use: β-blockers, long acting nitrates, CCBs for typical/STABLE angina
- Use: long-acting nitrates, CCBs for VARIANT angina

Front 35

What is the mechanism of action of Nitrates?

Back 35

- Denitrated in smooth muscle
- Free nitrate/nitrite converted to NO
- Activates GC → ↑cGMP
- Activates PKG → ↓Ca2+ and dephosphorylation of myosin

Front 36

What are the types of Nitrates?

Back 36

- Nitroglycerin
- Isosorbide Dinitrate
- Isosorbide Mononitrate

Front 37

What are the effects of Nitrates on an ischemic heart?

Back 37

- ↑ Venous Capacitance
- ↓ Preload
- ↓ Diastolic Wall Tension and ↓O2 demand

- Small ↓ Afterload
- ↓ Systolic Wall Tension
- Slight reflex tachycardia and ↑contractility d/t reduction in BP

- Coronary dilator
- Dilation of eccentric stenosis
- Dilation of collateral blood vessels

Front 38

What happens to the different nitrates in the liver?

Back 38

- Nitroglycerin: inactivated by Nitrate Reductase in liver (low bioavailability d/t extensive 1st pass metabolism)

- Isosorbide Dinitrate: metabolized in liver to form mononitrate (biologically active)

- Isosorbide Mononitrate: not metabolized in liver

Front 39

What drugs are used for acute therapy of angina? Method of administration?

Back 39

- Nitroglycerin: rapidly dissolvable tablets or aerosol spray both for sublingual administration (leads to high blood conc. rapidly)
- Fast onset and short duration of action

Front 40

What drugs are used for chronic therapy / prophylaxis of angina? Method of administration?

Back 40

- Isosorbide Dinitrate: longer duration of action (4-6 hrs); controlled release forms; 25% oral bioavailability
- Isosorbide Mononitrate: no 1st pass metabolism; t1/2 = 5 hrs
- Nitroglycerin: orally as controlled release or as patch / ointment / paste to skin

Front 41

What are the side effects of nitrate drugs?

Back 41

- Hypotension
- Flushing
- Tachycardia
- Throbbing headache

Front 42

What tolerance can be seen with nitrate drugs?

Back 42

- Complete tolerance can develop if continually used for more than a few hours
- Also reverses rapidly (24h after stopping drug)
- May be d/t depletion of tissue thiols or production of free radicals
- May be more common with patches

Front 43

What limits the effectiveness of the slow-release forms of nitrates?

Back 43

Tolerance can develop after more than a few hours

Front 44

What are some tips to avoid tolerance with nitrate drugs?

Back 44

- Use smallest effective dose
- Schedule nitrate-free period of at least 8 hours to reduce or prevent tolerance

Front 45

What drug can interact with nitrates and cause severe hypotension?

Back 45

PDE5 inhibitors (used to treat erectile dysfunction)
(eg, sildenafil, tadalafil, and vardenafil)

Front 46

How do β-blockers work for angina pectoris?

Back 46

- Used for chronic tx of typical / stable angina
- Not useful for vasospastic angina
- Block positive inotropic and chronotropic actions of catecholamines on heart (via β1 receptors)

Front 47

What are the effects of β-blockers on an ischemic heart?

Back 47

- ↓ O2 demand
- ↓ HR
- ↓ Contractility
- ↓ BP

- Small ↑ in O2 supply to ischemic areas
- ↑ Endocardial perfusion d/t ↓HR (more time in diastole)

- ↓ CO can lead to ↑preload that can result in ↑wall tension

Front 48

What are the ABSOLUTE contraindications of β-blockers?

Back 48

- Severe bradycardia
- High degree AV block
- Severe, unstable LV failure

Front 49

What are the RELATIVE contraindications of β-blockers?

Back 49

- Asthma and bronchospastic disease
- Severe depression
- Peripheral vascular disease
- Caution in: diabetes and coronary spasm

Front 50

How can Ca2+ Channel Blockers be used for angina?

Back 50

Chronic tx of both typical/stable angina and variant angina

Front 51

What are the effects of Ca2+ Channel blockers on an ischemic heart?

Back 51

- ↓ O2 demand
- ↓HR, contractility, and wall stress (d/t ↓afterload secondary to ↓BP)

- ↑ O2 supply
- ↑ Endocardial blood flow (by ↓HR) and coronary blood flow by dilating collaterals or eccentric stenoses)
- Relieves and prevents coronary spasms

Front 52

What are the dihydropyridines? What do they treat? Effects?

Back 52

- Nifedipine and Amlodipine
- Vasospastic Angina d/t pronounced vascular actions
- May aggravate typical/stable angina d/t reflex tachycardia (↑HR) in response to hypoTN (use w/ β-blocker)

Front 53

What are the non-dihydropyridines? What do they treat? Effects?

Back 53

- Verapamil and Diltiazem
- Typical/Stable Angina d/t greater effect on cardiac muscle to ↓O2 demand
- Use cautiously w/ β-blocker b/c it already ↓HR

Front 54

Which CCBs should be combined w/ a β-blocker? Why?

Back 54

- Nifedipine and Amlodipine
- Causes reflex tachycardia (β-blockers ↓HR)

Front 55

What are the benefits of combination nitrate + β-blocker therapy?

Back 55

Nitrates prevent (produced by β-blockers):
- ↑ diastolic wall tension
- Vasospasm

β-blockers prevent (produced by nitrates):
- ↑HR
- ↑Contractility

Both:
- ↓ Myocardial O2 demand (different mechanisms)
- ↑ Subendocardial blood flow (different mechanisms)

Front 56

What are the types of acute coronary syndromes?

Back 56

- ST elevated MI
- Unstable Angina
- Non-ST elevated MI

Front 57

What causes an acute coronary syndrome?

Back 57

- Plaque erodes or ruptures acutely
- Causes a thrombus formation and partial or complete coronary obstruction

Front 58

What is the difference between ST-elevated MI, Non-ST elevated MI, and unstable angina in terms of the lumen obstruction?

Back 58

- ST-elevated MI: thrombus completely obstructs lumen
- Non-ST elevated MI: platelets and thrombus partially obstruct lumen
- Unstable angina: platelets partially obstruct lumen

Front 59

What are the symptoms and causes of stable angina? How do you relieve symptoms?

Back 59

- Chest pain occurs in stable pattern over time
- Usually associated w/ exertion
- Pain is transient and relieved by rest or nitroglycerin

Front 60

What are the symptoms and causes of acute coronary syndrome? How do you relieve symptoms?

Back 60

- May be new-onset chest pain
- Accelerating in frequency, severity, and duration
- Occurs w/ low exertion or during rest
- NOT relieved by nitroglycerin (needs to be treated immediately)

Front 61

What causes and occurs in an ST-elevated MI (STEMI)?

Back 61

- Complete occlusion of diseased coronary artery
- Causes transmural ischemia and cell death = infarction
- Sx: chest pain

Front 62

What are the EKG and lab results that indicate an ST-elevated MI (STEMI)?

Back 62

- ST segment elevation
- Pathological Q wave - infarction
- Elevated MB-CK and cardiac troponins (cTnI and cTnT)
- Less specific for cardiac injury: CK, lactate dehydrogenase (LDH), aspartate transaminase (AST), myoglobin

Front 63

What causes and occurs in non-ST-elevated MI (NSTEMI)?

Back 63

- Partial thrombus formation after plaque disruption w/ partial occlusion of diseased vessel
- Ischemia is severe enough to cause subendocardial infarction and
- Serum biomarkers are elevated

Front 64

What causes and occurs in Unstable Angina?

Back 64

- Partial thrombus formation after plaque disruption w/ partial occlusion of diseased vessel
- Magnitude and severity of ischemia does NOT result in significant cell death
- Serum biomarkers are NOT elevated

Front 65

What are the EKG and lab results that indicate a non-ST-elevated MI (NSTEMI) or Unstable Angina?

Back 65

- EKG: indicates subendocardial ischemia
- ST segment depression
- T wave inversion

Front 66

How do you treat Acute Coronary Syndrome?

Back 66

- Anti-thrombotics (anti-platelets, anti-coagulants, HMG-CoA reductase inhibitors)
- Therapies to optimize oxygen supply/demand balance

Front 67

What are the drugs used to optimize oxygen supply and demand in acute coronary syndrome?

Back 67

- Nitroglycerin
- β-blockers
- Morphine (reduces pain and anxiety)
- O2

Front 68

What reperfusion therapy is used for a ST-elevated MI (STEMI)?

Back 68

Rapid reperfusion to limit infarct size:
- Percutaneous coronary intervention (PCI): angioplasty or stent placement

Thrombolysis:
- Alteplase and related thrombolytics

Front 69

What reperfusion therapy is used for non-ST-elevated MI (NSTEMI) and Unstable Angina?

Back 69

- Immediate reperfusion therapy is not indicated
- Manage medically
- Urgently (w/ 12-48 hours) assess need for revascularization

Front 70

What determines the prognosis of an Acute Coronary Syndrome?

Back 70

- Infarct size
- Early treatment to reduce rate of infarct progression (early reperfusion)

Front 71

Over what period of time is the ischemic area from infarction evolving? What does this mean?

Back 71

Over 6 hours (it takes 6 hours for myocardium to die, so you have that amount of time to get in there and salvage the myocardium)

Front 72

What is the cause of Ischemic Cardiomyopathy?

Back 72

- Coronary Artery Disease - causes impaired LV function (below normal ejection fraction)
- Damage from infarction
- Poor contractile function in regions w/ low blood flow

Front 73

How does Ischemic Cardiomyopathy change with time?

Back 73

Progressive w/ symptoms of clinical heart failure

Front 74

What are the heart changes in Ischemic Cardiomyopathy?

Back 74

- LV dilation and hypertrophy = Eccentric hypertrophy
- Dilated cardiomyopathy: chamber is dilated

Front 75

What revascularization techniques are used for Ischemic Cardiomyopathy?

Back 75

- PCI: Percutaneous Coronary Intervention (angiplasty or stent placement)
- CABG: Coronary Artery Bypass Grafting

Front 76

What are the goals of secondary prevention of Ischemic Heart Disease?

Back 76

- Reduce plaque progression
- Stabilize plaque
- Prevent thrombosis, should plaque rupture occur
- Reduce incidence of MI and death

Front 77

What therapies are used for secondary prevention of Ischemic Heart Disease?

Back 77

- Low dose Aspirin (75-162 mg/day)
- β-blockers
- ACE-Inhibitors

Front 78

What are the functions of low dose Aspirin (75-162 mg/day)? In what patients is this therapy utilized?

Back 78

- Used in patients w/ known Coronary Artery Disease
- Reduces plaque progression and stabilizes plaques
- Prevents thrombosis should plaque rupture occur

Front 79

What should be used in patients who are intolerant to Aspirin?

Back 79

Use ADP P2Y12 receptor blockers

Front 80

What are the functions of β-blockers for secondary prevention of ischemic heart disease? In what patients is this therapy utilized?

Back 80

- Secondary prevention in patients w/ infarction
- Reduces incidence of re-infarction and mortality after infarction
- Non-selective or β1-selective blockers are both effective
- Benefit related to: anti-arrhythmic effects, prevent post-infarction remodeling, preserve/improve ventricular function

Front 81

What are the functions of ACE-Inhibitors for secondary prevention of ischemic heart disease? In what patients is this therapy utilized?

Back 81

- Secondary prevention patients w/ infarction, particularly if ejection fraction is reduced
- Reduces mortality after infarction
- Prevents / reduces adverse remodeling
- Improves hemodynamics
- Reduces progression to congestive heart failure

Front 82

What should be used in patients who are intolerant to ACE-Inhibitors?

Back 82

Angiotensin Receptor Blocker (ARB)

Front 83

What drug should be used in patients with known coronary artery disease to prevent ischemic heart disease?

Back 83

Aspirin (75-162 mg/day)

Front 84

What drug should be used in patients with a history of infarction?

Back 84

β-blockers

Front 85

What drug should be used in patients with a history of infarction with a reduced ejection fraction?

Back 85

ACE-Inhibitors (or Angiotensin II Receptor Blockers)