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Cardiology > Anti-Ischemic Medications > Flashcards

Anti-Ischemic Medications Flashcards

1
Q

Myocardial Ischemia

  • Definition
  • Two types
A
  • Definition
    • When metabolic requirements of the myocyte exceed available supply of oxygen
  • Two types
    • Supply side ischemia
    • Demand side ischemia
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2
Q

Supply Side Ischemia

  • Definition
  • Affected by two factors
A
  • Definition
    • When myocardial oxygen supply doesn’t meet myocardial oxygen demand
  • Affected by two factors
    • Oxygen carrying capacity of blood
    • Coronary blood flow volume
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3
Q

Supply Side Ischemia: Oxygen Carrying Capacity

  • Determined by two factors
    • Oxygen supply
    • Hemoblogin content of the circulatory system
  • Normal circumstances
A
  • 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
  • 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
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4
Q

Supply Side Ischemia: Coronary Blood Flow Volume

  • Modulated through changes in…
  • Max during…
  • Increases as…
A
  • 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
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5
Q

Supply Side Ischemia: Coronary Flow Reserve

  • Regulates…
  • Modulated by…
  • 3 levels of vessel resistance in the coronary vasculature
  • Normal circumstances
A
  • 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
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6
Q

Supply Side Ischemia: Nitric Oxide

  • Regulates…
  • Life cycle
  • Treatment options
A
  • 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
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7
Q

Demand Side Ischemia

  • Definition
  • Altered by changes in…
A
  • Definition
    • When myocardial oxygen demand exceeds myocardial oxygen supply
  • Altered by changes in…
    • Heart rate
    • Myocardial contractility
    • Myocardial wall stress
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8
Q

Demand Side Ischemia: Heart Rate

  • Double product
  • Relationship
  • Treatment options
A
  • 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
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9
Q

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
A
  • 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
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10
Q

Demand Side Ischemia: Wall Stress

  • LaPlace’s Law
  • Relationships
  • Pharmacological manipulation
A
  • 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
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11
Q

3 Major Categories of Anti-Ischemic Medications

A
  • Nitrates
  • Beta adrenergic receptor antagonists
  • Calcium channel antagonists
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12
Q

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
  • Dosages
    • Lower dosages
    • Higher dosages
    • Other
A
  • 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: ↓
  • 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
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13
Q

Nitrates: Short vs. Long Acting

  • Short acting nitrates
    • Administration
    • Absorption
    • Onset & duration
    • Prophylactic use
  • Long acting nitrates
    • Administration
    • Isosorbide dinitrate (oral)
    • Isosorbide mononitrate (oral)
A
  • 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
  • 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
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14
Q

Nitrates: Side Effects

  • Nitrate tolerance (tachyphylaxis)
    • Definition
    • Prevented by…
  • Other side effects
A
  • 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
  • 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
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15
Q

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
A
  • 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)
  • 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)
  • Alpha receptors
    • Location
      • Found in peripheral circulation
    • Effects
      • Trigger peripheral vasoconstriction
      • Promote vasodilation –> decrease afterload
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16
Q

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
A
  • 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
17
Q

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
A
  • Cardioselective beta-1 blockers
    • Hydrophilic
      • Atenolol
      • Esmolol (IV)
    • Lipophilic
      • Metoprolol
      • Bisoprolol
      • Betaxolol
  • Cardioselective beta-1 blockers w/ ISA
    • Hydrophilic
      • Acebutolol
    • Lipophilic
  • Noncardioselective beta blockers (beta-1 & beta-2)
    • Hydrophilic
      • Nadolol
      • Timolol
    • Lipophilic
      • Propranolol
  • Noncardioselective beta blockers (beta-1 & beta-2) w/ ISA
    • Hydrophilic
      • Carteolol
    • Lipophilic
      • Pindolol
      • Penbutolol
  • Noncardioselective beta blockers (beta-1 & beta-2) w/ alpha-receptor blockade
    • Hydrophilic
      • Labetolol
    • Lipophilic
      • Carvedilol
18
Q

Beta-Adrenoreceptor Antagonists (Beta-Blockers): Metabolism

  • Hydrophilic (water soluble)
    • Half-lives
    • Excretion / metabolism
    • CNS effects
  • Lipophilic (lipid soluble)
    • Half-lives
    • Excretion / metabolism
    • CNS effects
A
  • 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
19
Q

Beta-Adrenoreceptor Antagonists (Beta-Blockers): Net Effects on Myocardial Supply & Demand

  • Supply side ischemia
  • Demand side ischemia
A
  • 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
20
Q

Beta-Adrenoreceptor Antagonists (Beta-Blockers): Adverse Effects

  • CNS
  • Conduction
  • Cardiac
  • Peripheral vasculature
  • Glycemia
A
  • 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”
  • 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)
21
Q

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
A
  • 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
  • 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
22
Q

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
A
  • 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
23
Q

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
A
  • 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
24
Q

Calcium Channel Antagonists: Adverse Side Effects

  • BP
  • Cardiac
  • Conduction
  • Edema
  • GI
  • Other
  • Mortality
A
  • 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
25
Q

Ranolazine: Mechanism

  • General mechanism
  • Mechanism of action
    • Stage 4
    • Stage 0
    • Stage 1
    • Stage 2
    • Stage 3
    • Stage 4
A
  • 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)
26
Q

Ranolazine: Effect on Ischemic Myocytes

A
  • 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
27
Q

Ranolazine: Adverse Side Effects & Metabolism

  • Adverse side effects
  • Metabolism
  • Contraindications
A
  • 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
28
Q

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
A
  • 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

Cardiology (40 decks)

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