Exam 2 - Drugs used in Heart failure and arrhythmias

Question 1

Define heart failure and its pathogenesis.

Answer 1

Heart failure occurs when the heart is unable to pump sufficient blood to meet the body’s demands. It results from conditions like coronary artery disease, hypertension, or cardiomyopathy, which damage the heart or increase its workload, leading to decreased cardiac output and fluid retention​. 5 year mortality is 50% with inadequate CO.
-Systolic is more acute, diastolic is more chronic.

Left ventricle = pulmonary congestion
right ventricle = peripheral congestion

Question 2

Compare the four factors of cardiac performance, and how they are altered in heart failure.

Answer 2

Preload: Increased in heart failure due to fluid retention.
Afterload: Often elevated due to increased vascular resistance.
Contractility: Reduced in heart failure as the heart muscle weakens.
Heart Rate: Often increased as compensation, but this is inefficient long-term​

Question 3

Define the Starling law.

Answer 3

The stroke volume of the heart increases in response to an increase in the volume of blood filling the heart (end-diastolic volume), up to a certain point. In heart failure, the heart is less responsive to increases in EDV.

Question 4

Discuss how the following all contribute to EDV: ESV, passive filling, atrial contraction.

Answer 4

End-Systolic Volume (ESV): Increased ESV results in higher EDV.
Passive Filling: Decreased in diastolic dysfunction, limiting EDV.
Atrial Contraction: Atrial systole contributes to EDV, especially important in conditions with impaired relaxation​

Question 5

How much ml is actually pumped out on average?

Answer 5

140mL in left ventricle, 90ml get pumped out.

Question 6

Describe the strategies and list the major drug groups used in the treatment of acute heart failure and chronic failure.

Answer 6

Acute HF: Diuretics, vasodilators (nitroprusside), positive inotropes (dobutamine).
Chronic HF: ACE inhibitors, β-blockers, aldosterone antagonists, diuretics​

Question 7

Draw the molecular mechanisms controlling normal cardiac contractility.

Answer 7

Dependent on calcium-induced calcium release from the sarcoplasmic reticulum, activating actin-myosin cross-bridging for contraction. Drugs like digoxin increase intracellular calcium to enhance contractility

Question 8

Describe the mechanism of action of digitalis and its major effects.

Answer 8

Inhibits the Na+/K+-ATPase pump, leading to increased intracellular calcium, which improves myocardial contractility. It also slows AV node conduction, useful in atrial fibrillation​

Increases PR interval, decreased QT interval.

Question 9

Describe the nature and mechanism of digitalis’s toxic effects on the heart.

Answer 9

Digitalis toxicity can cause arrhythmias (due to calcium overload), nausea, vomiting, and visual disturbances. Hyperkalemia, hypercalcemia, and hypomagnesia can exacerbate toxicity​.

Tachycardia, fibrillation, arrest

Question 10

List positive inotropic drugs other than digitalis that have been used in heart failure.

Answer 10

Dobutamine: β1 agonist that increases heart contractility and output.
Milrinone: Phosphodiesterase (PDE3) inhibitor (it degrades cAMP), increases cAMP, leading to enhanced calcium handling and contractility​

milirinone can also be used for pHTN

Question 11

Explain the beneficial effects of diuretics, vasodilators, ACE inhibitors, and other drugs that lack positive inotropic effects in heart failure.

Answer 11

Diuretics: Reduce preload by promoting fluid excretion.
Vasodilators: Decrease afterload, reducing the workload on the heart.
ACE Inhibitors: Prevent angiotensin II-mediated vasoconstriction and remodeling

Question 12

Discuss the reasoning behind giving beta-blockers for heart failure.

Answer 12

Beta-blockers reduce the harmful effects of chronic sympathetic stimulation on the heart (e.g., tachycardia, arrhythmias) and improve survival by reducing myocardial oxygen demand and remodeling​

Not given in acute HF

Question 13

Describe non-pharmaceutical intervention for HF.

Answer 13

Non-Pharmaceutical Interventions for Heart Failure:
Lifestyle modifications include salt restriction, fluid management, weight loss, and exercise. Devices like pacemakers or implantable cardioverter defibrillators (ICDs) may be needed in advanced cases​

Question 14

List the different types of arrhythmias.

Answer 14

Different Types of Arrhythmias:
Atrial Fibrillation (AFib): Characterized by disorganized atrial activity, causing an irregular and often rapid heartbeat. It increases the risk of stroke due to thrombus formation in the atria.
Atrial Flutter: Similar to AFib but involves more regular, rapid atrial contractions (usually a “sawtooth” pattern on EKG).
Ventricular Tachycardia (VT): A fast heart rate originating from the ventricles, often associated with poor cardiac output and risk of deterioration to ventricular fibrillation.
Ventricular Fibrillation (VF): Life-threatening arrhythmia with uncoordinated contraction of the ventricles, leading to no effective pumping of blood and requiring immediate defibrillation.
Heart Block: Refers to delayed or blocked conduction between the atria and ventricles. There are different degrees (first, second, and third-degree block) depending on the severity​

Question 15

Illustrate the intrinsic conduction system and subsequent EKG reading.

Answer 15

The intrinsic conduction system includes the SA node, AV node, bundle of His, right and left bundle branches, and Purkinje fibers. The SA node initiates the heartbeat, causing atrial depolarization (P wave on EKG). The AV node delays the signal slightly, allowing the ventricles to fill before they contract (represented by the PR interval). The QRS complex reflects ventricular depolarization, while the T wave shows ventricular repolarization​

Question 16

Compare the different types of ion channels, their operation, and contribution to the cardiac action potential.

Answer 16

Sodium Channels (Na+): Rapidly open to allow sodium influx during depolarization (Phase 0), initiating the action potential. These channels close during the refractory period.
Calcium Channels (Ca2+): Open during Phase 2 (plateau phase), allowing calcium entry, which maintains depolarization and triggers contraction in the cardiac muscle.
Potassium Channels (K+): Open during Phase 3 (repolarization), allowing potassium to exit the cell, restoring the negative resting membrane potential. Their activity is crucial for resetting the cardiac cell for the next action potential​

Question 17

Describe the process of sodium channel recycling and the positions of the m and h gates.

Answer 17

Sodium Channel Recycling (m & h Gates):
M Gate (Activation Gate): Closed at rest but opens rapidly when the membrane is depolarized, allowing Na+ to enter the cell.
H Gate (Inactivation Gate): Closes shortly after depolarization to stop further Na+ influx and prevent excessive depolarization. During repolarization, the h gate reopens, and the m gate closes, resetting the sodium channel for the next action potential. This process is essential for the rapid firing of action potentials in the heart​

Question 18

Draw the cardiac action potential including the phases and what is occurring at each phase.

Answer 18

Cardiac Action Potential Phases:
Phase 0 (Depolarization): Rapid Na+ influx through sodium channels causes a sharp upward spike.
Phase 1 (Initial Repolarization): Na+ channels close, and K+ begins to exit the cell, causing a slight dip.
Phase 2 (Plateau): Ca2+ influx balances out K+ efflux, maintaining the depolarized state, crucial for prolonged contraction (sustained systole).
Phase 3 (Repolarization): K+ efflux predominates, returning the membrane potential to its resting state.
Phase 4 (Resting Membrane Potential): The Na+/K+ ATPase pump restores ion gradients, preparing the cell for the next action potential​

Question 19

Differentiate disturbances in impulse formation and impulse conduction.

Answer 19

Impulse Formation: Occurs when abnormal automaticity or triggered activity generates ectopic beats (beats that originate from a location other than the SA node). Examples include premature atrial or ventricular contractions.

Impulse Conduction: Involves issues like reentry circuits (as seen in atrial flutter or ventricular tachycardia) or conduction blockages, such as AV block, which slow or completely block electrical signals traveling through the heart​

Question 20

Describe EKG differences in heart block

Answer 20

First-Degree Heart Block: Prolonged PR interval (>0.20 seconds), indicating delayed conduction through the AV node but no missed beats.
Second-Degree Heart Block (Mobitz Type I - Wenckebach): Progressive PR interval lengthening until a QRS complex is dropped, then the cycle repeats.
Second-Degree Heart Block (Mobitz Type II): Sudden dropped QRS complexes without PR interval prolongation, which may progress to third-degree block.
Third-Degree Heart Block: Complete dissociation between atrial and ventricular activity; P waves and QRS complexes occur independently

Question 21

Describe the function and distinguishing components of the 4 major groups of antiarrhythmic drugs.

Answer 21

Four Major Groups of Antiarrhythmic Drugs:
Class I (Na+ Channel Blockers): Reduce the rate of depolarization (Phase 0). Subdivided into:
IA (Quinidine): Prolongs action potential duration, used in atrial and ventricular arrhythmias.
IB (Lidocaine): Shortens action potential, used in ventricular arrhythmias, especially post-MI.
IC (Flecainide): Markedly slows conduction, used in refractory arrhythmias.
Class II (Beta-Blockers): Decrease heart rate and AV conduction by blocking β1 receptors, used in atrial arrhythmias and post-MI (e.g., metoprolol).
Class III (K+ Channel Blockers): Prolong repolarization and action potential duration, used in severe arrhythmias (e.g., amiodarone).
Class IV (Ca2+ Channel Blockers): Slow AV node conduction, used in atrial fibrillation and flutter (e.g., verapamil)​

Question 22

List 1 or 2 of the most important drugs in each of the 4 groups (and 3 subgroups of I) of antiarrhythmics. List the major toxicities of those drugs.

Answer 22

Class IA: Quinidine (prolongs QT, risk of torsades de pointes).
Class IB: Lidocaine (CNS toxicity at high doses, including seizures).
Class IC: Flecainide (proarrhythmic in patients with structural heart disease).
Class II: Metoprolol (bradycardia, hypotension).
Class III: Amiodarone (pulmonary fibrosis, thyroid dysfunction).
Class IV: Verapamil (constipation, bradycardia)​(Ch 11 - Antihypertensiv…).

Question 23

Describe the effects of adenosine of SVT

Answer 23

Adenosine works by transiently hyperpolarizing the AV node and interrupting reentry circuits that cause supraventricular tachycardia (SVT). It’s given as a rapid IV bolus and has a very short half-life (~10 seconds). Patients often feel a transient sensation of flushing or chest discomfort due to the brief asystole that may follow the administration​

Question 24

List non-pharmacological therapy for arrhythmias

Answer 24

Pacemakers: Used for bradyarrhythmias or heart blocks to ensure a regular rhythm by providing electrical impulses to the heart.
Implantable Cardioverter-Defibrillators (ICDs): Detect and treat life-threatening ventricular arrhythmias (like ventricular tachycardia or fibrillation) by delivering a shock to restore normal rhythm.
Catheter Ablation: A procedure used to destroy abnormal electrical pathways in the heart that cause arrhythmias, often used for atrial fibrillation, atrial flutter, or Wolff-Parkinson-White syndrome

Question 25

Organize the anti-arrhythmia drugs based on treatment use in acute and chronic care.

Answer 25

Acute:
Adenosine: Used in acute SVT to terminate the arrhythmia.
Amiodarone: Used in acute management of ventricular arrhythmias, especially in cases of ventricular tachycardia or fibrillation.

Chronic:
Beta-Blockers: Used long-term to control rate and rhythm in atrial fibrillation or to prevent sudden cardiac death post-MI.
Amiodarone: Used for chronic management of refractory arrhythmias due to its broad antiarrhythmic properties​