Cardiac Physiology and Pharmacology Quiz
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Questions and Answers

What happens when the membrane potential (Em) equals the Nernst potential for potassium (EK)?

  • There is no net flux of K+ across the membrane. (correct)
  • K+ influx occurs.
  • K+ efflux occurs.
  • The cell becomes hyperpolarized.

    • How does the influx of K+ affect the membrane potential in a state of hyperkalemia?

  • It maintains the membrane potential at -70 mV.
  • It causes a net efflux of Na+.
  • It causes depolarization of the membrane potential. (correct)
  • It makes the membrane potential more negative.

    • Which equation represents the relationship of the ion concentration ratios to the equilibrium potential (EX)?

  • EX = 31/Z log[Xo]/[Xi]
  • EX = 91/Z log[Xi]/[Xo]
  • EX = 61/Z log[Xi]/[Xo]
  • EX = 61/Z log[Xo]/[Xi] (correct)

    • What is the role of voltage-gated sodium channels in cardiac cells?

    <p>They initiate action potentials during depolarization.</p> Signup and view all the answers

    What effect does an Em of -80 mV have when compared to EK of -70 mV?

    <p>Encourages K+ influx.</p> Signup and view all the answers

    What happens during the efflux of K+ when Em is more positive than EK?

    <p>Membrane potential becomes more negative.</p> Signup and view all the answers

    How does a change in membrane potential influence ion flow across the membrane?

    <p>It influences whether the membrane potential moves towards or away from equilibrium potential.</p> Signup and view all the answers

    Which characteristic is NOT a property of voltage-gated ion channels?

    <p>They conduct ions in a uniform manner.</p> Signup and view all the answers

    What is a major adverse effect associated with sotalol therapy?

    <p>Torsades de pointes</p> Signup and view all the answers

    What is the primary mechanism of action of dofetilide?

    <p>Potent and selective IKr blocking</p> Signup and view all the answers

    Which drug should be avoided due to its contraindication with dronedarone?

    <p>Ketoconazole</p> Signup and view all the answers

    In which setting must therapy with sotalol be initiated?

    <p>Hospital inpatient</p> Signup and view all the answers

    What can be a potential effect of dronedarone on renal function?

    <p>Increase in serum creatinine without a reduction in renal function</p> Signup and view all the answers

    What is the primary role of the activation and inactivation processes of voltage-gated sodium channels in cardiomyocytes?

    <p>To ensure effective spread of electrical activity for coordinated heart contraction</p> Signup and view all the answers

    Which pharmacological receptor type couples to and activates inward rectifier (Kir) currents?

    <p>M2 muscarinic receptors</p> Signup and view all the answers

    What is the result of furosemide-induced hypokalemia in relation to the QT interval?

    <p>It prolongs the QT interval.</p> Signup and view all the answers

    Which mechanism can lead to ectopic automaticity in cardiac tissues?

    <p>Afterdepolarizations due to calcium overload</p> Signup and view all the answers

    What phase of cardiac conduction does reentry (circus movement) primarily affect?

    <p>Cardiac electrical signal pathways</p> Signup and view all the answers

    What does an increase in adrenergic tone affect regarding IKs channels?

    <p>It increases IKs activity.</p> Signup and view all the answers

    What condition increases susceptibility to early afterdepolarizations (EADs) in cardiomyocytes?

    <p>Congenital long QT syndrome</p> Signup and view all the answers

    In which setting can triggered activity occur as a consequence of afterdepolarizations?

    <p>In cases of hypokalemia and myocardial ischemia</p> Signup and view all the answers

    What does the term 'action potential duration' refer to in cardiac myocytes?

    <p>The duration of electrical activity in a single heartbeat</p> Signup and view all the answers

    Which current primarily contributes to the early component of the sodium current (INa) during an action potential?

    <p>Voltage-gated sodium current</p> Signup and view all the answers

    What effect do shortened refractory periods and reduced conduction velocity have on the heart?

    <p>They promote reentry phenomena.</p> Signup and view all the answers

    Which subclass of Class I antiarrhythmic drugs is characterized by causing a moderate reduction in Phase 0 slope and increasing effective refractory period?

    <p>Subclass IA</p> Signup and view all the answers

    Which of the following antiarrhythmic drugs primarily blocks Na+ channels in ventricular myocytes?

    <p>Lidocaine</p> Signup and view all the answers

    What is a key characteristic of Class III antiarrhythmic agents?

    <p>They cause a delay in repolarization and prolong the refractory period.</p> Signup and view all the answers

    Which of the following is NOT included in the Vaughn-Williams classification?

    <p>Class II - K+ channel blockers</p> Signup and view all the answers

    Which drug is used for atrial and ventricular arrhythmias and increases the effective refractory period?

    <p>Procainamide</p> Signup and view all the answers

    What is the primary action of β-adrenergic blockers in the treatment of arrhythmias?

    <p>Block myocardial β-adrenergic receptors</p> Signup and view all the answers

    What is the main pharmacological effect of flecainide?

    <p>Inhibits cardiac sodium channels, Nav1.5</p> Signup and view all the answers

    Which antiarrhythmic drug class includes agents that markedly slow conduction without significantly affecting action potential duration?

    <p>Class IC</p> Signup and view all the answers

    Which of the following best describes the action of dofetilide?

    <p>Prolongs action potential by delaying K+ efflux</p> Signup and view all the answers

    What is the primary use of lidocaine in antiarrhythmic therapy?

    <p>Acute intravenous therapy of ventricular arrhythmias</p> Signup and view all the answers

    Which of the following drugs is specifically classified as a Class IV antiarrhythmic?

    <p>Diltiazem</p> Signup and view all the answers

    Which of the following best describes the action of Dronedarone?

    <p>It has similar characteristics to other antiarrhythmic classes.</p> Signup and view all the answers

    Which antiarrhythmic drug is an orally effective congener of lidocaine?

    <p>Mexilitine</p> Signup and view all the answers

    What cardiovascular effect does propanolol primarily exert?

    <p>Reduces automaticity of the SA node</p> Signup and view all the answers

    Which calcium channel blocker is known to also block Na+ channels in addition to Ca2+ channels?

    <p>Verapamil</p> Signup and view all the answers

    What is a common noncardiac adverse effect associated with flecainide?

    <p>Blurred vision</p> Signup and view all the answers

    Which class of antiarrhythmic drugs can achieve rate-dependent control of arrhythmias?

    <p>Class II and IV</p> Signup and view all the answers

    What is the mechanism of action of calcium channel blockers in relation to the AV node?

    <p>Decrease automaticity</p> Signup and view all the answers

    Which of the following antiarrhythmic drugs has the highest incidence of proarrhythmia?

    <p>Ibutilide</p> Signup and view all the answers

    What is a common adverse effect associated with calcium channel blockers?

    <p>Flushing</p> Signup and view all the answers

    Which class of antiarrhythmic drugs is commonly used for maintaining sinus rhythm in patients with atrial fibrillation?

    <p>Class IA</p> Signup and view all the answers

    Which antiarrhythmic drug is delivered with the highest initial dose in the treatment protocol?

    <p>Amiodarone</p> Signup and view all the answers

    What role do the activation and inactivation processes of voltage-gated sodium channels play in cardiomyocytes?

    <p>They ensure the coordinated spread of electrical activity.</p> Signup and view all the answers

    Which factors can influence the QT interval through indirect effects?

    <p>Increased sympathetic tone</p> Signup and view all the answers

    What is the mechanism behind ectopic automaticity in cardiac tissues?

    <p>It arises from triggered activity and abnormal depolarizations.</p> Signup and view all the answers

    What causes early afterdepolarizations (EADs) in cardiomyocytes?

    <p>Loss of repolarization reserve</p> Signup and view all the answers

    What is a potential adverse effect of propranolol when used with vasopressors like epinephrine?

    <p>Acute hypertensive episodes</p> Signup and view all the answers

    Which of the following best describes a reentry circuit in cardiac muscle?

    <p>It creates a circuitous pathway that can recur abnormally.</p> Signup and view all the answers

    What is a key characteristic of inward rectifiers (Kir) in cardiac cells?

    <p>They facilitate significant inward currents at negative membrane voltages.</p> Signup and view all the answers

    Which condition is NOT an indication for the use of amiodarone?

    <p>Sinus bradycardia</p> Signup and view all the answers

    What is the primary pharmacological action of amiodarone?

    <p>Decrease automaticity</p> Signup and view all the answers

    Which condition can increase the susceptibility to adverse cardiac events due to EADs?

    <p>Congenital long QT syndrome</p> Signup and view all the answers

    Which substance primarily affects the trafficking or expression of cardiac ion channels?

    <p>Glucose</p> Signup and view all the answers

    Which of the following is a characteristic effect of amiodarone?

    <p>Blockade of Ca2+ and Na+ channels</p> Signup and view all the answers

    What phenomenon leads to afterdepolarizations and triggered activity in the myocardium?

    <p>Decreased intracellular ATP levels</p> Signup and view all the answers

    What is a major potential toxicity associated with amiodarone?

    <p>Pulmonary toxicity</p> Signup and view all the answers

    What happens when the membrane potential (Em) is more positive than the equilibrium potential (EK) for K+?

    <p>K+ efflux makes the membrane potential more negative.</p> Signup and view all the answers

    How does dronedarone differ from amiodarone?

    <p>It is a structurally modified derivative aimed at reducing toxicities</p> Signup and view all the answers

    Which equation calculates the equilibrium potential for a given ion?

    <p>Eion = 61/Z log([Xo]/[Xi])</p> Signup and view all the answers

    In the context of treating arrhythmias, which of the following describes a key function of beta-adrenergic blockers?

    <p>Decrease myocardial contractility</p> Signup and view all the answers

    Which effect is specifically associated with the administration of high-dose intravenous amiodarone?

    <p>Bradyarrhythmias</p> Signup and view all the answers

    What defines the state when no net ion movement occurs across the membrane?

    <p>When membrane potential equals the Nernst potential for that ion.</p> Signup and view all the answers

    Which ion channel feature contributes to the variability in conductance among voltage-gated ion channels?

    <p>Inconsistent gating mechanisms among the family.</p> Signup and view all the answers

    What occurs during a hyperkalemic state in terms of K+ movement?

    <p>K+ influx occurs, depolarizing the cell.</p> Signup and view all the answers

    Which characteristic of voltage-gated sodium (Nav) channels is critical for their function in depolarization?

    <p>Rapid inactivation following activation.</p> Signup and view all the answers

    What role does the Nernst equation play in understanding ion movement across the membrane?

    <p>It calculates the equilibrium potential that influences ion flux.</p> Signup and view all the answers

    Which statement about the relationship between membrane potential and ion concentration is accurate?

    <p>Membrane potential adjusts to bring ion flow closer to equilibrium potential.</p> Signup and view all the answers

    Which antiarrhythmic agent is known to have the lowest incidence of proarrhythmia?

    <p>Amiodarone</p> Signup and view all the answers

    What is the primary mechanism by which calcium channel blockers affect the AV node?

    <p>Block slow inward Ca2+ current</p> Signup and view all the answers

    Which of the following antiarrhythmic drugs can be classified as a Class IC agent?

    <p>Flecainide</p> Signup and view all the answers

    What is a common adverse effect of calcium channel blockers?

    <p>Flushing</p> Signup and view all the answers

    In the context of atrial fibrillation, what is the significance of early rhythm-control therapy?

    <p>It aims to restore and maintain sinus rhythm.</p> Signup and view all the answers

    What is a primary consequence of reduced conduction velocity in the context of atrial fibrillation?

    <p>Enhanced reentry phenomena</p> Signup and view all the answers

    Which class of antiarrhythmic agents is characterized by causing a pronounced decrease in Phase 0 slope?

    <p>Class I-C</p> Signup and view all the answers

    Which of the following antiarrhythmic drugs is known to prolong repolarization and has a broad range of effects?

    <p>Amiodarone</p> Signup and view all the answers

    What mechanism is primarily responsible for the action of β-adrenergic blocking agents?

    <p>Blockade of myocardial β-adrenergic receptors</p> Signup and view all the answers

    Which subclass of Class I antiarrhythmic drugs is known for having little effect on the effective refractory period?

    <p>Subclass IC</p> Signup and view all the answers

    What is a distinguishing feature of Class III antiarrhythmics compared to Class I antiarrhythmics?

    <p>Delay repolarization</p> Signup and view all the answers

    Which of the following statements accurately describes a common feature of Class I antiarrhythmic drugs?

    <p>They can be subclassified based on their effects on Phase 0 slope.</p> Signup and view all the answers

    What potential side effect is associated with the use of procainamide?

    <p>Prolonged QT interval</p> Signup and view all the answers

    Which antiarrhythmic drug primarily blocks Na+ channels in ventricular myocytes?

    <p>Lidocaine</p> Signup and view all the answers

    Which antiarrhythmic drug also possesses weak β-blocking properties?

    <p>Propafenone</p> Signup and view all the answers

    What is the primary mechanism of action of Ranolazine in treating chronic angina?

    <p>Blocks sodium channel late phase influx</p> Signup and view all the answers

    Which of the following effects is NOT associated with adenosine’s action on adenosine receptors?

    <p>Stimulates norepinephrine release</p> Signup and view all the answers

    What is the indication for using Ivabradine in clinical practice?

    <p>Management of chronic stable angina in patients unable to take beta blockers</p> Signup and view all the answers

    Which adverse effect is commonly associated with adenosine?

    <p>Asthma – dyspnea – chest pain</p> Signup and view all the answers

    What regulatory approval did Ivabradine receive in 2015?

    <p>For treatment of chronic stable angina</p> Signup and view all the answers

    Study Notes

    Antiarrhythmic Drugs

    • Antiarrhythmic drugs are used to treat abnormal heart rhythms
    • Different classifications exist based on mechanisms of action
    • These mechanisms include Na+ channel blockade, β-adrenergic receptor blockade, prolong repolarization (K+ channel blockade), Ca2+ channel blockade, adenosine, and digitalis glycosides.

    Electrical and Chemical Gradients for K+ and Na+ in a Resting Cardiac Cell

    • Potassium (K+) concentration inside a cardiac cell is 4mM, outside is 150mM
    • Sodium (Na+) concentration inside a cardiac cell is 10mM, outside is 140mM
    • Membrane potentials for both ions are 0mV to 90mV.
    • Electrical gradients are from outside to inside
    • Concentration gradients are from high to low concentration

    Timing of Life's Fundamental Events

    • Fast events involve electrical signaling
    • 1 day - DNA replication and cell division
    • 1 hour - Gene transcription; protein synthesis
    • 1 minute - Hormone regulation
    • 0.1-1 second - Typical enzyme activity
    • 1 millisecond - Electrical signaling, vision, hearing, nerve conduction, muscle contraction

    Voltage-gated Ion Channel Superfamily

    • More than 140 members
    • Conductance varies by 100-fold
    • Variable gating
    • K+, Ca2+, Na+
    • Bacterial ancestor likely similar to KcsA channel

    Nernst Equation

    • Equilibrium potential is the membrane potential that balances diffusion gradients
    • Depends on the ratio of ion concentration on both sides of the membrane
    • Allows calculation of theoretical potential for a given ion
    • Ex = 61/Z log[X+]o/[X+]i, where:
      • Ex = equilibrium potential for ion in millivolts (mV)
      • [X+]o = concentration of ion outside the cell
      • [X+]i = concentration of ion inside the cell
      • Z = valence of ion

    Control of Membrane Potential

    • If membrane potential equals the Nernst potential for an ion, there is no net flux
    • Varying membrane potential affects ion flux
    • Hyperkalemia increases intracellular K+ causing influx and depolarization
    • When Em is positive to Ek, K+ efflux causes hyperpolarization

    Functional Properties of Voltage-Gated Sodium Channels

    • Inactivation state makes cardiomyocytes resistant to immediate second action potential firing
    • Activation and inactivation processes ensure appropriate temporal and directional spread of electrical activity
    • Coordinated contraction is necessary to propel blood throughout the body

    Electrical Signal of a Single Sodium Channel

    • 15 picoamp (pAmp)
    • 10 million Na+ ions per second
    • One trillionth of the typical 15 Amp household wall socket

    Conformational Cycle of a Voltage-gated Sodium Channel

    • Resting, depolarization, activated, inactivated, hyperpolarization, inactivation

    Voltage-gated Sodium Channel

    • Extracellular and intracellular components are visualized

    Structural and Pharmacological Characterization of Voltage-Gated Sodium Channels

    • Structural components of the channel are shown
    • Drugs and molecules interacting with the channel are visualized

    Action Potential Waveforms and Underlying Ionic Currents in Adult Human Cardiac Myocytes

    • Action potential phases: rapid depolarization (0), partial repolarization (1), plateau (2), repolarization (3), pacemaker depolarization (4)
    • Ionic current changes (Na+, K+, and Ca2+) accompany the action potential phases
    • Conduction of the impulse through the heart, with the ECG trace

    Pacemaking Mechanisms

    • Mechanisms of control for pacemaking are shown
    • Ion channels are mentioned

    Temporal Relationship Between AP, Cytoplasm Ca2+, and Contraction

    • Relationship of action potential, calcium, and contraction are shown

    Congenital Long-QT Syndrome: Channelopathies

    • Long QT Syndrome, prolongation of QT interval, syncope, and sudden death described
    • Genes and proteins associated with the syndrome are listed

    hERG Current and LQTS

    • hERG current is associated with LQTS
    • Action potential waveforms and ionic currents shown

    M₂ Muscarinic and A₁ Adenosine Receptors Coupling to and Activating Kir Currents

    • Mechanism showing inward rectifier K+ channels

    Early and Late Components of Sodium Current (INa)

    • Shows early and late sodium current
    • Calcium, late sodium, and hERG potassium

    Indirect Effects on QT Interval

    • QT interval affects are shown

    Electrical Remodeling in Heart Failure (HF)

    • Electrical remodeling in heart failure is shown with associated genes and proteins

    Mechanisms of Cardiac Arrhythmias

    • Ectopic automaticity
    • Afterdepolarizations and triggered activity
    • Reentry

    Mechanisms of Ectopic Firing

    • Enhanced automaticity
    • Early afterdepolarizations (EADs)
    • Delayed afterdepolarizations (DADs)

    Afterdepolarizations and Triggered Activity

    • Hypokalemia, congenital long QT syndrome, loss of repolarization reserve, drug-induced action potential duration

    Reentry Circuit in Small Branches of Purkinje System

    • Circus movement (reentry excitation) in heart muscle
    • Shortened refractory period and reduced conduction velocity promote reentry

    AF Mechanisms

    • Ectopic focus, single-circuit reentry, multiple-circuit reentry mechanisms for AF

    Abnormal Impulse Formation or Propagation Underlying Atrial Fibrillation

    • Abnormal impulse propagation (vulnerable substrate) and abnormal impulse formation (ectopic activity) are underlying atrial fibrillation

    Vaughn-Williams Classification

    • Based on cellular properties of normal His-Purkinje cells
    • Classification based on drugs’ ability to block specific ionic currents and adrenergic receptors

    Antiarrhythmic Agents

    • Vaughan-Williams Classification scheme:
      • Class I - Na+ channel blockers
      • Class II - Sympatholytic agents
      • Class III - Prolong repolarization
      • Class IV - Ca2+ channel blockers
      • Purinergic agonists
      • Digitalis glycosides

    Antiarrhythmic Drug Mechanisms

    • Na+ channel blockade
    • β-adrenergic receptor blockade
    • Prolong repolarization (K+ channel blockade)
    • Ca2+ channel blockade
    • Adenosine
    • Digitalis glycosides.

    Classification of Antiarrhythmics: Subclass IA

    • Cause moderate reduction in Phase 0 slope
    • Increase effective refractory period (ERP)
    • Increased action potential duration (APD)
    • Includes quinidine, procainamide, disopyramide

    Classification of Antiarrhythmics: Subclass IB

    • Small decrease in Phase 0 slope
    • May decrease ERP
    • May decrease APD
    • Brief duration of blockade
    • Negligible interaction with voltage-gated K+ channels.
    • Preferentially interacts with inactivated sodium channels
    • Includes lidocaine and mexiletine

    Classification of Antiarrhythmics: Subclass IC

    • Pronounced decrease in Phase 0 slope
    • Markedly slow conduction
    • Little effect on APD and ERP
    • Long duration of blockade
    • Includes flecainide and propafenone

    Class I Antiarrhythmic Drugs

    Class II Antiarrhythmics

    • Based on two major actions (ß-adrenergic blockade and Na+ channel blockade)
    • Includes propranolol, metoprolol, atenolol, sotalol, and esmolol

    Class III Antiarrhythmics

    • Cause delay in repolarization and prolonged refractory period
    • Includes amiodarone, ibutilide, bretylium, dofetilide

    Class IV Antiarrhythmics

    • Slow rate of AV-conduction
    • Includes verapamil and diltiazem

    Antiarrhythmic Drugs List

    • Quinidine
    • Procainamide
    • Disopyramide
    • Lidocaine
    • Mexiletine
    • Flecainide
    • Propafenone
    • Propranolol
    • Metoprolol
    • Atenolol
    • Sotalol
    • Esmolol
    • Amiodarone
    • Ibutilide
    • Bretylium
    • Dofetilide
    • Verapamil
    • Diltiazem
    • Adenosine
    • Digoxin
    • Atropine

    Lidocaine

    • Blocks both open and inactivated cardiac Na+ channels
    • Decreases automaticity, especially in ectopic pacemakers
    • Not useful for atrial arrhythmias

    Adverse Reactions for Lidocaine

    • Large intravenous doses may produce seizures.
    • Tremor, dysarthria, and altered levels of consciousness more common

    Mexiletine

    • Congener of lidocaine
    • Orally effective
    • Used in the treatment of ventricular arrhythmias

    Flecainide

    • Potent inhibitor of cardiac sodium channels (Nav1.5)
    • Very long recovery from Na+ channel block
    • Blocks ryanodine receptor calcium release channels
    • Cornerstone rhythm control strategy for AF without structural heart disease, but with adverse effects.

    Adverse Effects of Flecainide

    • Dose-related blurred vision is a common non-cardiac adverse effect
    • Has negative inotropic effects
    • Does not cause EADs or torsades de pointes
    • Maintenance of sinus rhythm in patients with supraventricular arrhythmias
    • Increased mortality (2.5-fold) in patients convalescing from myocardial infarction

    -adrenergic Receptor Blockers: Propranolol

    • β-blockade
    • Quinidine-like effect
    • Reduces automaticity of SA node
    • Reduces automaticity and conduction velocity in AV node, His Purkinje and ventricles
    • May reverse effects of epinephrine on mean arterial pressure

    Effects of Vasoconstrictor on Local Anesthetic Action

    • Duration of anesthesia

    Cardiovascular Effects of Epinephrine

    • Patients medicated with nonselective beta-blockers

    Administration of Epinephrine

    • Administration of epinephrine after propranolol

    Adverse Effects of Propranolol

    • Reduced myocardial contractility, bradycardia, angina upon sudden withdrawal, bronchospasm
    • Used for supraventricular tachycardia

    Amiodarone HCl – Pharmacologic Effects

    • Widely-used antiarrhythmic
    • Indications: unstable VT, VF, SVT, and AF
    • Class III effects: duration of action potential and effective refractory period
    • Systemic toxicity: pulmonary toxicity and bradyarrhythmias with loading dose

    Amiodarone Actions

    • Blocks Na+, Ca2+, and β-adrenoceptors
    • Delays repolarization and increases refractory period via K+ channel blockade
    • Decreases automaticity
    • Slows conduction
    • A vasodilator

    Dofetilide

    • A "pure" class III antiarrhythmic
    • Potent and selective Ikr blocker
    • Can prolong the QT interval (1-3% incidence of torsades)
    • Therapy must be initiated in a hospital
    • Maintenance of sinus rhythm in patients with atrial fibrillation

    Proarrhythmia: Torsades de Pointes

    • Class IA (quinidine, procainamide, disopyramide): 2-9%, 2-3%, 2-3%
    • Class III (d,l-sotalol, ibutilide, dofetilide, amiodarone): 1-5%, 1-2%, 6%, 1-3%, < 1%

    Early Rhythm-Control Therapy in Patients with Atrial Fibrillation (EAST-AFNET 4)

    • First primary outcome: events/person-year
    • Cardiac outcomes: death from cardiovascular causes, stroke, hospitalization with worsening of heart failure or acute coronary syndrome, and second primary outcome
    • Efficacy of early rhythm control compared to usual care

    Guideline recommendations for antiarrhythmic drug use in patients with AF

    • No structural heart disease
    • Structural heart disease: CAD, HF

    Catheter Ablation or Antiarrhythmic Drugs for Ventricular Tachycardia

    • Survival free of primary end-point
    • Comparison of catheter ablation with drug therapy (sotalol or amiodarone)

    Calcium Channel Blockers: Verapamil, Diltiazem

    • Block slow inward Ca2+ current
    • Reduce automaticity
    • Increase refractory period and decrease conduction velocity of AV Node
    • Inhibit contractility
    • Vasodilation

    Calcium Channel Blockers (Adverse Effects)

    • Flushing
    • Reduced contractility of the heart
    • AV node conduction defects
    • Constipation
    • Used for supraventricular arrhythmias

    Self-administered intranasal etripamil for atrioventricular-nodal-dependent SVT

    • Cumulative conversion rate (%)
    • Symptom-prompted, repeat-dose regimen

    Ranolazine

    • Initially approved for treatment of chronic angina pectoris
    • Beneficial antianginal effects and unique antiarrhythmic efficacy in AF and ventricular tachyarrhythmias
    • Works primarily by preferentially blocking Na+ channel late phase of influx
    • Less [Na+], allows Na+/Ca2+ exchanger to operate in normal forward mode
    • Also blocks Ikr at therapeutic concentrations

    Ivabradine

    • Approved by FDA for treatment of chronic stable angina
    • Reduces heart rate through inhibition of the If current
    • Exerts an antianginal effect

    Adenosine (Adenocard®)

    • Released by most cells
    • Normal plasma levels ~300 nM
    • Can reach micromolar levels in ischemic tissue

    Adenosine Receptors

    • Four receptor subtypes (A1, A₂A, A₂B, A₃) classified
    • All four are G-protein coupled receptors
    • Methylxanthines (caffeine, theophylline) are competitive antagonists

    Adenosine (Effects)

    • Stimulates adenosine receptors (A1 receptors in the heart)
    • Increases K+ conductance
    • Inhibits opening of Ca²⁺ channels
    • Reduces norepinephrine release
    • Reduces automaticity and AV nodal conduction

    Adenosine (Adverse Effects)

    • Flushing
    • Asthma
    • Dyspnea
    • Chest pain
    • SA nodal arrest
    • AV nodal block

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