Anti-Ischemic Medications Flashcards
Myocardial Ischemia
- Definition
- Two types
- Definition
- When metabolic requirements of the myocyte exceed available supply of oxygen
- Two types
- Supply side ischemia
- Demand side ischemia
Supply Side Ischemia
- Definition
- Affected by two factors
- Definition
- When myocardial oxygen supply doesn’t meet myocardial oxygen demand
- Affected by two factors
- Oxygen carrying capacity of blood
- Coronary blood flow volume
Supply Side Ischemia: Oxygen Carrying Capacity
- Determined by two factors
- Oxygen supply
- Hemoblogin content of the circulatory system
- Normal circumstances
- Determined by two factors
- Oxygen supply
- Environmental factors: changes in altitude or inhaled FiO2
- Intrinsic factors: underlying lung disease due to emphysema or pneumonia
- Hemoglobin content of the circulatory system
- Influenced by conditions like anemia or alterations in oxygen binding capacity of hemoglobin
- Seen w/ hemoglobinopathies like sickle cell disease or methemoglobinemia
- Oxygen supply
- Normal circumstances
- Oxygen carrying capacity remains constant
- Myocardial oxygen extraction is nearly max at rest
- Acute changes in myocardial oxygen supply occur primarily through changes in coronary blood flow volume
Supply Side Ischemia: Coronary Blood Flow Volume
- Modulated through changes in…
- Max during…
- Increases as…
- Modulated through changes in…
- Coronary artery perfusion pressure (directly)
- Extrinsic compressive forces on the coronary artery (indirectly)
- Intrinsic coronary artery resistance (indirectly)
- Max during…
- Ventricular diastole when extrinsic compressive forces exerted on the coronary vessels by LV systolic contraction are minimized
- Increases as…
- Intrinsic vascular resistance decreases
Supply Side Ischemia: Coronary Flow Reserve
- Regulates…
- Modulated by…
- 3 levels of vessel resistance in the coronary vasculature
- Normal circumstances
- Regulates…
- Intrinsic coronary vascular resistance
- Modulated by…
- Changes in arteriolar smooth muscle tone via regulation of Ca2_ channel activity
- 3 levels of vessel resistance in the coronary vasculature
- R1: epicardial conductance
- R2: precapillary arterioles
- R3: microcirculation / capillary beds
- Normal circumstances
- Autoregulation of intrinsic vascular resistance occurs primarily in R2 & R3 vessels
- Vasodilitation occurs in response to metabolic stress / myocardial ischemia due to mycoardial supply-demand mismatch

Supply Side Ischemia: Nitric Oxide
- Regulates…
- Life cycle
- Treatment options
- Regulates…
- Coronary blood flow in R2 vessels
- NO: arteriolar & venodilator
- Production of NO (endothelium-derived relaxing factor, EDRF) secondarily activates myogenic & endothelium dependent vasodilatation
- Life cycle
- Activation of endothelial NO synthetase (eNOS)
- NO produced by intact endothelium from L-arginine
- Diffuses across endothelium
- Coverts GTP to cGMP via guanylate cyclase
- Decreases cytosolic Ca2_ concentration
- Triggers smooth muscle relaxation, vasodilation, & increased myocardial blood suply
- Treatment options
- NO may treat supply side ischemia

Demand Side Ischemia
- Definition
- Altered by changes in…
- Definition
- When myocardial oxygen demand exceeds myocardial oxygen supply
- Altered by changes in…
- Heart rate
- Myocardial contractility
- Myocardial wall stress
Demand Side Ischemia: Heart Rate
- Double product
- Relationship
- Treatment options
- Double product
- Myocardial oxygen demand / consumption = HR & systemic BP
- Relationship
- Linear relationship b/n HR & myocardial oxygen uptake
- Physicla stressors –> increase HR –> increase myocardial oxygen consumption
- Treatment options
- Attenuation of this chronotropic response w/ anti-adrenergic agents (ex. beta-blockers) can help treat myocardial ischemia
Demand Side Ischemia: Myocardial Contractility
- Peripheral oxygen requirements
- Cardiac output
- Stroke volume
- Myofibril contractility is regulated by changes in..
- Myocyte excitation-contraction coupling
- Beta adrenergic system
- Ca2+ channel & beta-adrenergic receptor antagonists
- Peripheral oxygen requirements
- Increase w/ exercise
- Trigger events that lead to increased cardiac output to meet demands of peripheral metabolism
- Cardiac output
- CO = HR & SV
- Stroke volume
- Modulated by changes in myofibril contractility
- Myofibril contractility is regulated by changes in…
- Loading conditions of the heart
- Sympathetic tone
- Myocyte excitation-contraction coupling
- Transmembrane Ca2+ influx into the myocyte via L-type Ca2+ channels
- Ca2+-induced Ca2+ channel release: activated ryanodine receptors trigger a larger efflux of Ca2+ from the SR
- Surge in intracellular Ca2+ binds troponin-C
- Troponin-C inhibits troponin-I to expose active sites on thin actin
- Intercalation of thick myosin heads w/ subsequen myofibril contraction
- Increased cytosolic Ca2+ –> increased myocardial contractility –> increased metabolic activity & oxygen demand
- Beta adrenergic system
- Beta-1 adrenergic receptor stimulation
- Activation of Gs protein
- Activation of adenylate cyclase
- cAMP production
- Activation of L-type Ca2+ channels
- Ca2+-induced Ca2+ channel release from the SR
- Increased myocardial contractility & oxygen consumption
- Ca2+ channel & beta-adrenergic receptor antagonists
- Inhibit the myocyte excitation-contraction coupling response & the beta adrenergic system
- Treat MI

Demand Side Ischemia: Wall Stress
- LaPlace’s Law
- Relationships
- Pharmacological manipulation
- LaPlace’s Law
- Myocardial wall stress = (P * R) / 2h
- Myocardial wall stress varies directly w/ LV pressure (P) & radius (R)
- Myocardial wall stress varies indirectly w/ myocardial wall thickness (h)
- Relationships
- Decrease LV pressure & radius + increase LV wall thickness –> reduce wall stress & myocardial oxygen consumptoin
- Alter LV pressure, radius, & wall thickeness by changing preload & afterload
- Pharmacological manipulation
- Manipulating LV pressure, radius, & wall thickness can manage demand side ischemia & chronic coronray artery ischemia

3 Major Categories of Anti-Ischemic Medications
- Nitrates
- Beta adrenergic receptor antagonists
- Calcium channel antagonists
Nitrates: Mechanism of Action
- Nitrate conversion
- Net effects of nitrates in managing coronray artery disease
- Supply
- Coronary blood flow: vascular resistance
- Coronary blood flow: extrinsic vompression
- Diastolic perfusion time
- Collateral circulation
- Demand
- Heart rate
- Contractility
- Wall tension: preload
- Wall tension: afterload
- Supply
- Dosages
- Lower dosages
- Higher dosages
- Other
- Nitrate conversion
- Mitochondrial aldehyde dehydrogenase converts exogenous nitrates to NO using sulfhydryl group cofactors
- Net effects of nitrates in managing coronray artery disease
- Supply
- Coronary blood flow: vascular resistance: ↓↓↓
- Coronary blood flow: extrinsic vompression: ↓↓
- Diastolic perfusion time: 0 or ↓
- Collateral circulation: ↑
- Demand
- Heart rate: 0 or ↑
- Contractility: 0 or ↑
- Wall tension: preload: ↓↓↓
- Wall tension: afterload: ↓
- Supply
- Dosages
- Lower dosages
- Venodilation –> decreased preload, myocardial wall tension, & myocardial oxygen demand
- Higher dosages
- Arterial vasodilation –> increased myocardial blood supply
- Other
- Recruitment of collateral vessels –> increased myocardial blood supply from non-ischemic to ischemic territories
- Lower dosages

Nitrates: Short vs. Long Acting
- Short acting nitrates
- Administration
- Absorption
- Onset & duration
- Prophylactic use
- Long acting nitrates
- Administration
- Isosorbide dinitrate (oral)
- Isosorbide mononitrate (oral)
- Short acting nitrates
- Administration
- Mucosal absorption: sublingual tablets or oral spray
- Transdermal absorption: nitroglycerin ointment
- Absorption
- Bypasses enteral absorption
- Avoids first pass metabolism in the liver
- Provides rapid, transient delivery of meds directly into the bloodstream within minutes
- Onset & duration
- Brief onset allows treatment of acute angina
- Brief duration deactivates the drug by hepatic metabolism within 30-60 minutes
- Prophylactic use
- Used prior to activities that can trigger angina
- Can improve exercise tolerance for 30-40 minutes
- Administration
- Long acting nitrates
- Administration
- Oral forms
- Sustained release transdermal patch
- Isosorbide dinitrate (oral)
- Enteral absorption –> rapid first pass hepatic metabolism
- Variable drug bioavailability
- Renally excreted
- Dosed 2x/day
- Isosorbide mononitrate (oral)
- Doesn’t undergo significant first-pass hepatic metabolism
- Greater bioavailability
- Dosed 1x/day
- Administration
Nitrates: Side Effects
- Nitrate tolerance (tachyphylaxis)
- Definition
- Prevented by…
- Other side effects
- Nitrate tolerance (tachyphylaxis)
- Definition
- In patients taking chronic long acting nitrates, drug effect becomes less potent over time
- Prevented by…
- Adjusting the nitrate dosing interval to provide a 10-12 hour nitrate free interval (at night) to allow for resensitization
- Removing time released transdermal nitroglycerin patches at night & reapplying them in the morning
- Definition
- Other side effects
- Headache & flushing (common)
- Related to vasodilation of meningeal & cutaneous blood vessels
- Hypotension
- From venous & arterial dilation in the presence of intravascular volume depletion
- Hypoxemia (uncommon)
- Inhibition of vasoconstriction in regions of pulmonary hypoventilation –> ventilation/perfusion mismatch
- Tissue hypoxia (rare)
- In patients w/ methemoglobinemia
- Hypotension w/ phosphodiesterase inhibitors
- Phosphodiesterase inhibitors (ex. sildenafil) are contraindicated
- Headache & flushing (common)
Beta-Adrenoreceptor Antagonists (Beta-Blockers): Types of Adrenoreceptors
- Beta-adrenoreceptor antagonists
- Beta-1 receptors
- Location
- Effects
- Treatment
- Beta-2 receptors
- Location
- Effects
- Side effects
- Alpha receptors
- Location
- Effects
- Beta-adrenoreceptor antagonists
- Exert their effect on the CV system through competitive inhibition of effects of endogenous catecholamines
- Beta-1 receptors
- Location
- Found in myocardium & specialixed conduction tissue
- Effects
- Increase myocyte contractility
- Accelerate SA node depolarization
- Accelerate His-Purkinje system conduction
- Treatment
- Treat ischemic heart disease by decreasing chronotropic & myocardial contractile responses during physcial stress (ex. exercise)
- Location
- Beta-2 receptors
- Location
- Found in peripheral & coronary circulation & in pulmonary bronchioles
- Effects
- Promote dilation of peripheral vasculature
- Promote relaxation of pulmonary bronciholes
- Side effects
- Claudication in patients w/ peripheral vascular disease
- Coronary vasospasm in patients w/ vasospastic (Prinzmetal’s) angina
- Bronchospasm in patients w/ reactive airway disease (ex. asthma)
- Location
- Alpha receptors
- Location
- Found in peripheral circulation
- Effects
- Trigger peripheral vasoconstriction
- Promote vasodilation –> decrease afterload
- Location

Beta-Adrenoreceptor Antagonists (Beta-Blockers): Characteristics
- Cardioselective beta blockers
- Examples
- Lower doses
- Higher doses
- Intrinsic sympathomimetic activity (ISA)
- Examples
- Effects
- As endogenous catecholamine levels rise w/ exercise…
- Uses
- Alpha-adrenoreceptor blocking activity
- Examples
- Effects
- Uses
- Third generation beta-blockers
- Cardioselective beta blockers
- Ex. atenolol & metoprolol
- Lower doses
- Preferentially block beta-1 receptors
- Beta-1 selective agents are better tolerated in patients w/ mild asthma or peripheral vascular disease
- Higher doses
- Cardoiselective properties are reduced –> non-beta-1 receptor selective
- Intrinsic sympathomimetic activity (ISA)
- Ex. pindolol & acebutolol
- Effects
- Partial agonists
- Weak agonists that competitively block beta adrenoreceptors from the effects of potent endogenous catecholamines
- Induce less bradycardia & negative inotropic effects at rest than beta blockers w/o ISA
- As endogenous catecholamine levels rise w/ exercise…
- Agents “shield” the beta adrenoreceptor from more potent effects of circulating catecholamines
- Agents reduce exercise-associated increases in HR & myocardial contractility
- Uses
- Limited, never first line agents in treating ischemic heart disease
- May increase mortality in patients w/ coronary artery disease
- Alpha-adrenoreceptor blocking activity
- Ex. labetolol & carvedilol
- Effects
- Prevent unopposed alpha-adrenergic receptor stimulation in peripheral vasculature when peripheral beta-2 receptors are inhibited
- Limit peripheral vasoconstriction
- Uses
- Treat HTN
- Not used as firs tline agents in treating ischemic coronary artery disease b/c their potency varies
- Third generation beta-blockers
- Ex. carvedilol & bucindolol
- Improve survival in patients w/ LV systolic dysfunction
Beta-Adrenoreceptor Antagonists (Beta-Blockers): Characteristics & Metabolism
- Cardioselective beta-1 blockers
- Hydrophilic
- Lipophilic
- Cardioselective beta-1 blockers w/ ISA
- Hydrophilic
- Lipophilic
- Noncardioselective beta blockers (beta-1 & beta-2)
- Hydrophilic
- Lipophilic
- Noncardioselective beta blockers (beta-1 & beta-2) w/ ISA
- Hydrophilic
- Lipophilic
- Noncardioselective beta blockers (beta-1 & beta-2) w/ alpha-receptor blockade
- Hydrophilic
- Lipophilic
- Cardioselective beta-1 blockers
- Hydrophilic
- Atenolol
- Esmolol (IV)
- Lipophilic
- Metoprolol
- Bisoprolol
- Betaxolol
- Hydrophilic
- Cardioselective beta-1 blockers w/ ISA
- Hydrophilic
- Acebutolol
- Lipophilic
- Hydrophilic
- Noncardioselective beta blockers (beta-1 & beta-2)
- Hydrophilic
- Nadolol
- Timolol
- Lipophilic
- Propranolol
- Hydrophilic
- Noncardioselective beta blockers (beta-1 & beta-2) w/ ISA
- Hydrophilic
- Carteolol
- Lipophilic
- Pindolol
- Penbutolol
- Hydrophilic
- Noncardioselective beta blockers (beta-1 & beta-2) w/ alpha-receptor blockade
- Hydrophilic
- Labetolol
- Lipophilic
- Carvedilol
- Hydrophilic
Beta-Adrenoreceptor Antagonists (Beta-Blockers): Metabolism
- Hydrophilic (water soluble)
- Half-lives
- Excretion / metabolism
- CNS effects
- Lipophilic (lipid soluble)
- Half-lives
- Excretion / metabolism
- CNS effects
- Hydrophilic (water soluble)
- Longer half-lives
- Renally excreted
- Fewer CNS side effects
- Lipophilic (lipid soluble)
- Shorter half-lives
- Hepatically metabolized
- Cross the BBB more readily
Beta-Adrenoreceptor Antagonists (Beta-Blockers): Net Effects on Myocardial Supply & Demand
- Supply side ischemia
- Demand side ischemia
- Supply side ischemia: improve
- Decrease heart rate
- Increase diastolic filling time
- Increase coronary blood flow by icnreasing vascular resistance & extrinsic compression
- Demand side ischemia: prevent
- Decrease heart rate
- Decrease myocardial contractility
- Bradycardia –> increase diastolic filling time –> increase preload
- Nominal effect relative to other favorable effects of this class of drug
Beta-Adrenoreceptor Antagonists (Beta-Blockers): Adverse Effects
- CNS
- Conduction
- Cardiac
- Peripheral vasculature
- Glycemia
- CNS
- Fatigue
- Disrupted sleep patterns
- Sexual dysfunciton
- Depression
- Treatment: dose reduciton or converstion to a more hydrophilic beta blocker
- Conduction
- Sinus bradycardia
- AV nodal blockade
- Treatment: avoid beta blockers in patients w/ symptomatic bradycardia & conduction disease
- Cardiac
- Congestive heart failure in patients w/ LV dysfunction
- Long term benefit of neurohormonal blockade in patients w/ LV dysfunction extends beyond the anti-ischemic effects of this group of drugs
- Treatment: ensure patients w/ LV dysfunction are euvolemic before starting a beta blocker
- Once initiated, “start low & go slow”
- Congestive heart failure in patients w/ LV dysfunction
- Peripheral vasculature
- Exacerbate peripheral vascular disease in patients w/ atheroslcerosis or vasospasms (ex. Raynaud’s phenomenon)
- Glycemia
- Inhibiting beta2-receptor-mediated glycogenolysis –> insulin-induced hypoglycemia (life threatening in brittle diabetics)
Calcium Channel Antagonists
- General effects
- Dihydropyridine
- First generation examples & effects
- Second generation examples & effects
- Non-dihydropyridine
- General effects
- Benzothiazapine: first generation examples & effects
- Phenylalkylamine: first generation examples & effects
- General effects
- Manage ishcemic heart disease in patients who are beta blocker intolerant
- Noncompetitivley inhibit L-type Ca2+ channels in cardiac & smooth muscle cells
- –> decreased mycoardial contractility
- –> increased coronary peripheral arterial vasodilation
- Dihydropyridine
- First generation
- Ex. Nifedipine
- More potent peripheral vasodilators
- Little direct effect on SA node function
- Induce reflex tachycardia in response to their potent vasodilator effects
- Second generation
- Ex. Amlodipine, Felodipine, Nicardipine, Isradipine
- More vasoselective
- First generation
- Non-dihydropyridine
- General effects
- More potent effect on SA & AV node Ca2+ channel recovery
- More pronounced negative chronotropic & dromotropic effects on the cardiac conduction system
- May –> symptomatic sinus bradycardia & AV nodal blockade
- Benzothiazapine: first generation
- Ex. Diltiazem
- Safely used in combination w/ a beta blocker
- Monitor HR & PR-interval
- Phenylalkylamine: first generation
- Ex. Verapamil
- Shouldn’t be used in combination w/ a beta blocker due to eincreased incidence of complete heart block
- General effects
Calcium Channel Antagonists: Net Effects on Myocardial Oxygen Supply & Demand
- Dihydropyridine Ca2+ channel blockers
- Examples
- Effect on myocardial supply
- Effect on myocardial demand
- Non-dihydropyridine Ca2+ channel blockers
- Examples
- Effect on myocardial supply
- Effect on myocardial demand
- Dihydropyridine Ca2+ channel blockers
- Ex. nifidepine, amlodipine, felodipine
- Increase myocardial supply
- Increase coronary blood flow by decreasing vascualr resistance & extrinsic compression
- Increase collateral circulation
- Decrease myocardial demand
- Increase heart rate
- Increase or slighly decrease contractility
- Decrease wall tension by decreasing systemic vascular resistance & afterload
- May increase adrenergic tone –> reflex tachycardia
- Non-dihydropyridine Ca2+ channel blockers
- Ex. diltiazem, verapamil
- Increase myocardial supply
- Decrease heart rate
- Increase coronary artery vasodilation by decreasing vascular resistance
- Increase diastolic perfusion time
- Increase collateral circulation
- Decrease myocardial demand
- Decrease heart rate
- Decrease contractility
- Decreae peripheral vascular resistance by decreasing afterload & slightly increasing preload
Calcium Channel Antagonists: Metabolsim
- Metabolism
- Availability
- Bioavailability
- Drugs that increase Ca2+ channel antagonist bioavailability
- Drugs that increase cyclosporine bioavailability
- Drugs that increase serum digoxin levels
- Metabolism
- All hepatically metabolized
- Exceptoin: diltiazem undergoes hepatic metablism & renal excretion
- Availability
- Both short & extended release preparations
- Bioavailability
- Affected by drugs which are hepatically metabolized
- Influnece the metabolism of other medications
- Drugs that increase Ca2+ channel antagonist bioavailability
- Cimetidine (H2 blocker)
- Phenytoin
- Carbamezapine
- Drugs that increase cyclosporine bioavailability
- Diltiazem
- Verapamil
- Drugs that increase serum digoxin levels
- Verapamil
Calcium Channel Antagonists: Adverse Side Effects
- BP
- Cardiac
- Conduction
- Edema
- GI
- Other
- Mortality
- Hypotension
- Dihydropyridines
- CHF exacerbation
- Non-dihydropyridines
- Conduction abnormalities
- Sinus bradycardia & AV block in non-dihydropyridines (verapamil)
- Edema
- Due to augmented peripheral vasodilation
- GI
- Nause & constipation due to GI smooth muscle relaxation
- Gingival hyperplasia
- Rare
- Possible increase in CV mortality
- Short acting nifedipine may increase CV mortality in patients w/ coronary artery disease
- Potent peripheral vasodilation –> increased adrenergic tone
- Not seen w/ long acting nifedipine
- Administer w/ a beta blocker
- Short acting nifedipine may increase CV mortality in patients w/ coronary artery disease
Ranolazine: Mechanism
- General mechanism
- Mechanism of action
- Stage 4
- Stage 0
- Stage 1
- Stage 2
- Stage 3
- Stage 4
- General mechanism
- Treats stable angina w/o altering HR, BP, or contractility
- Decreases myocardial wall tension by preventing intracellular Ca2+ overload in the ischemic myocyte
- Inhibits the delayed INa & IKr channels of the myocardial AP
- Mechanism of action
- Stage 4
- Resting myocyte cell membrane potential is maintained by the IK1 current, Na/Ca pump, Na/K pump, & ICl current
- Stage 0
- Rapid depolarization
- Voltage gated Na channels activate
- Stage 1
- Rapid repolarization
- Membrane potential overshoots –> Na channels inactivate
- Delayed Na channels remain active
- Ranolazine exerts its effect through the inhibition of this delayed Na current
- Stage 2
- Plateau phase
- L-type Ca2+ channels activate
- Influex of extracellular Ca2+ into the myocyte
- Ca2+ induced Ca2+ channel release from the SR
- Myofibril contraction
- Stage 3
- Repolarization
- Delayed K currents activate
- Stage 4
- Diastolic relaxation & restoration of the resting cell membrane potential
- Intracellular Ca2+ is pumped back into the SR via the SERCA pump
- Ca2+ is transported from the intracellular to extracellular space by the Na/Ca exchanger (1 Ca2+ for 3 Na)
- Stage 4

Ranolazine: Effect on Ischemic Myocytes
- Ischemic myocytes –> increased late Na current –> increased intracellular Na
- Decreased Na/Ca pump electrochemical gradient for Ca2+
- Increased intracellular Ca2+
- Increased actin-myosin filament interaction
- Increased myocardial wall tension & oxygen demand
- Demand side ischemia
- Increased compressive forces on the intramyocardial coronary vessels
- Decreased myocardial oxygen supply
- Supply side ischemia
- Ranolazine
- Inhibits delayed Na current
- Favorably effects coronary blood flow supply-demand mismatch
- Inhibits extrinsic compression
- Inhibits wall tension
Ranolazine: Adverse Side Effects & Metabolism
- Adverse side effects
- Metabolism
- Contraindications
- Adverse side effects
- High doses –> inhibit delayed K currents –> QT prolongation & torsade de pointes
- Metabolism
- Metabolized by the CYP3a system in the liver w/ some renal clearance
- Drug levels increase when given w/ meds that inhibit the CYP3a system or in patients w/ impaired hepatic function
- –> increased risk of QT prolongation & torsade de pointe
- Contraindications
- Liver disease
- Strong CYP3a inhibitors (ex. ketoconazole (antifungal))
- Decrease ranolazine dose w/ moderate CYP3a inhibitors (ex. diltiazem, verapamil)
- Macrolide antibiotics (ex. clarithromycin)
- Antiretroviral agents to treat HIV
- Digoxin levels should be followed when taking both digoxin & ranolazine
Summary
- Main anti-ischemic medications
- Medications w/ additional benefits in preventing recurrent CV events & cardiac mortality
- Beta blockers w/o ISA
- Long acting nitrates
- Short acting nitrates
- Non-dihydropyridine Ca2+ channel blockers
- Triple drug therapy & novel agents like ranolazine
- Main anti-ischemic medications
- Beta blockers
- Nitrates
- Ca2+ channel blockers
- Medications w/ additional benefits in preventing recurrent CV events & cardiac mortality
- Aspirin
- HMA-CoA reductasae inhibitors
- ACE-inhibitors
- Clopidogrel
- Beta blockers w/o ISA
- First line therapy in patients w/ chronic ischemic heart disease
- Favorable effects on supply-demand ischemia
- Prevent sudden cardiac death following MI
- Prevent adverse effects of neurohormonal activation in patients w/ ischemic cardiomyopathy
- Initiated & dosages titrated to achieve adequate beta receptor blockade
- Demonstrated by resting bradycardia & attenuation in exercise-induced increases in heart rate
- Long acting nitrates
- Administred w/ an appropriate nitrate free interval
- Added when patients have persistent angina despite optimal beta blocker dose
- No additional survival benefit in patients w/ angina on medical therapy
- Short acting nitrates
- Used as needed in response to episodes of acute angina
- Used prophylactically prior to activites that produce angina
- Non-dihydropyridine Ca2+ channel blockers
- Used in patients w/ contraindications to beta blockade
- Triple drug therapy & novel agents like ranolazine
- May be required in patients w/ refractory symptoms
