Antiarrhythmic Drugs (part 2)

Question 1

Arrhythmia =

Answer 1

any rhythm that is not a normal sinus rhythm with normal atrioventricular (AV) conduction

any rhythm that is not a normal sinus rhythm with normal atrioventricular (AV) conduction

Question 2

Bradyarrhythmias:

Answer 2

HR < 50-60 bpm
- Sick sinus syndrome
- Atrio-ventricular conduction block

Question 3

Tachyarrhythmias:

Answer 3

HR > 100 bpm

Question 4

Supraventricular tachyarrhythmias

Answer 4

due to abnormal electrical signals originating above the ventricles

Question 5

Paroxysmal tachycardia :

Answer 5

HR 150-250 bpm

Question 6

Atrial Flutter:

Answer 6

atria beat at 250-350 bpm, regular heart rhythm

Question 7

Atrial Fibrillation:

Answer 7

atria beat up to 500 bpm, irregular rhythm, uncoordinated contraction

Question 8

Ventricular tachyarrhythmias

Answer 8

due to abnormal electrical signal originating in ventricles

Question 9

Ventricular Tachycardia:

Answer 9

> 120 bpm, regular heart rhythm

Question 10

Ventricular Fibrillation:

Answer 10

irregular rhythm with uncoordinated contraction, immediate cause of death

Question 11

Arrhythmia caused by:

Answer 11

Alteration in the movement of ions responsible for the action potentials in the pacemaker cells, conduction system and/or muscle.

Question 12

What are the important ions in the action potential?

Answer 12

1. Pacemaker (slow) cells (SA node, AV node)
   - Ca and K are most important.
2. Conduction and muscle (fast) cells (atria, purkinje fibers, ventricles)
   - Na, Ca and K are most important

Question 13

What are the causes of cardiac arrhythmias?

Answer 13

• Insufficient OXYGEN to myocardial cells
• ACIDOSIS or accumulation of waste products
• ELECTROLYTE disturbances
• STRUCTUAL DAMAGE of the conduction pathway
• DRUGS (e.g. antiarrhythmics, psychotropics and antihistamines)

Question 14

What are the mechanisms of cardiac arrhythmias?

Answer 14

1. Abnormal impulse formation
   aka: ECTOPIC FOCI = pacemaker of abnormal origin
   A) Abnormal automaticity
   - SA node (altered regular pacemaker activity) enhanced activity of spontaneous pacemakers
   B) Triggered activity
   
   • disturbances in repolarization triggers EARLY AFTERDEPOLARIZATIONS (EADs) in ATRIA or VENTRICLES
     –> long QT/torsade de points
2. Abnormal conduction
   - impaired AV node (heart block) leads to bradyarrhythmias
   - RE-ENTRY (circus) conduction leads to tachyarrhythmias

Question 15

Describe where ACh is

Answer 15

• neurotransmitter
• released from parasympathetic nerves
• acts on muscarinic receptors

phase 4 - slows depolarization rate
- decreases automaticity (SA node),

• slowed conduction (AV node)

Question 16

Describe where Norepinephrine/Epinephrine is

Answer 16

• neurotransmitter
• released from sympathetic nerves
• acts on β1-adrenergic receptors
• phase 4 - increases depolarization rate and reduces AP firing threshold
• increases automaticity (SA node), increased conduction (AV node)

Question 17

What may trigger Torsade de pointes?

Answer 17

Early Afterdepolarizations (EADs)

Question 18

What is Torsade de pointes?

Answer 18

twisting of the points (looks like a party streamer)

conditions/drugs which PROLONG the QT interval may precipitate these

Question 19

Torsade de pointes

Answer 19

characterized by twisting of isoelectric points on ECG and
prolonged QT interval

inherited and/or DRUG INDUCED (increased QT interval)

can lead to ventricular fibrillation and sudden death

responds to MAGNESIUM

Question 20

What do drug induced increase in QT interval include?

Answer 20

include:
- antiarrhythmics (Class Ia and III)
- antihistamines (e.g. seldane)
- anti-psychotics
- antibiotics (e.g. erythromycin)

• can cause sudden death
• hERG assays now routine during drug development

Question 21

What does re-entry require?

Answer 21

• available circuit (closed conduction loop)
• unidirectional block
• different conduction speed in limbs of circuit: conduction time (CT) > effective refractory period (ERP)

Question 22

Where does re-entry occur?

Answer 22

can occur in any part of the heart
- within a small region of the atria or ventricles
- within the AV node
- between atria and ventricles, etc
- accounts for most tachyarrhythmias in cardiac patients

Question 23

What happens when re-entry is localized to atria/ventricles?

Answer 23

when localized to atria/ventricles, re-entry can be stopped by converting the UNIDIRECTIONAL block INTO BI-directional block
- In NON-PACEMAKER (FAST) cells; this can be done with drugs that BLOCK Na+ CHANNELS DIRECTLY (Class I drugs) or by drugs that REDUCE Na+ CHANNEL ACTIVITY INDIRECTLY (Class III drugs; they delay repolarization which slows recovery of Na+ channels from inactivation)

Question 24

A special case of reentry in the AV node:

Answer 24

• paroxysmal supraventricular tachycardia (PSVT)
  – cause not clear and is often short lasting

Question 25

What is the re-entry in the AV node (special case) controlled by?

Answer 25

controlled by drugs that depress AV conduction, causing bidirectional block - calcium channel blockers (Class IV) - β-adrenergic receptor blockers (Class II) - Adenosine (Class V)

Question 26

Wolff-Parkinson-White Syndrome

Answer 26

in some cases an abnormal electrical pathway connecting the atria and ventricles may be present

Question 27

What is Wolff-Parkinson-White Syndrome?

Answer 27

- alternative conduction pathway -- ventricles back to atria (bundle of Kent) - incidence is less than 3% population -- often asymptomatic and rarely fatal - catheter ablation of abnormal electrical pathway is the preferred long-term approach

Question 28

What should you avoid if patient has Wolff-Parkinson-White Syndrome?

Answer 28

Avoid AV node blockers if atrial fibrillation or flutter - β-adrenergic receptor blocker , calcium antagonist, adenosine or digoxin

Question 29

What are the Mechanisms of Action of Antiarrhythmic Drugs?

Answer 29

1. Reducing Automaticity 2. Blocking Re-entry Mechanisms 3. Normalize Ventricular Rate (SUPRA-VENTRICULAR tachycardia) --> by slowing conduction through the AV node

Question 30

Mechanisms of Action of Antiarrhythmic Drugs 1) Reducing Automaticity A) Abnormal automaticity B) Triggered activity

Answer 30

A) slow the rate of spontaneous Phase 4 depolarization by blocking B1 receptors or Ca2+ channels --> reduced pacemaker activity B) by blocking open & inactivated Na+ or Ca2+ channels in depolarized tissues --> reduced triggered activity

Question 31

Mechanisms of Action of Antiarrhythmic Drugs 2) Blocking Re-entry Mechanisms

Answer 31

1) Reduce Phase 0 depolarization (CLASS I, II or IV) Slows conduction in the ischemia area converts region of UNIDIRECTIONAL BLOCK TO BIDIRECTIONAL BLOCK 2) prolong the action potential repolarization (CLASS III K channel blockers) increases the effective refractory period (ERP) conduction time < ERP = re-entry blocked

Question 32

Mechanisms of Action of Antiarrhythmic Drugs 3) Normalize Ventricular Rate (SUPRA-VENTRICULAR tachycardia)

Answer 32

slowing AV nodal conduction beta-blockers (Class II), calcium channel blockers (Class IV), adenosine and digoxin --> reduces ventricular rate --> increasing time for ventricular filling from atrium --> improves stroke volume (SV) --> increases cardiac output (CO = HR x ↑↑SV) --> improved hemodynamics

Question 33

What are the Class I antiarrhythmia drugs?

Answer 33

(procainamide, lidocaine, flecainide) - primarily block Na channels

Question 34

What are the Class II antiarrhythmia drugs?

Answer 34

(propranolol, metoprolol, esmolol) - primarily block B-adrenergic receptors

Question 35

What are the Class III antiarrhythmia drugs?

Answer 35

(amiodarone, sotalol) - primarily block K channels

Question 36

What are the Class IV antiarrhythmia drugs?

Answer 36

(verapamil) - primarily block Ca channels

Question 37

What are the Class V antiarrhythmia drugs?

Answer 37

(magnesium, adenosine, digoxin) - other mechanisms

Question 38

What are the 3 subclasses of Na+ channel blockers?

Answer 38

IA - procainamide moderate Na+ channel blockade; dissociates from the channel with intermediate kinetics IB - lidocaine weak Na+ channel blockade; dissociates from the channel with rapid kinetics IC – flecainide strong Na+ channel blockade; dissociates from the channel with slow kinetics

Question 39

What is the treatment of Bradycardia?

Answer 39

symptomatic bradycardia (< 50-60 bpm) – PACEMAKER

Question 40

What is the treatment of Tachycardia?

Answer 40

- isolated ectopic beats or short runs of tachycardia -- if Asymptomatic - no treatment - Symptomatic/severe tachycardia – IMMEDIATE CARDIOVERSION (ELECTRICAL/PHARMACOLOGICAL)

Question 41

What is the treatment of Atrial Fibrillation?

Answer 41

- anticoagulation (prior to cardioversion, if possible) - antiarrhythmics: 1) ventricular rate control (BY TARGETING AV NODE) - verapamil, beta-blocker, digoxin: target AV node to reduce ventricular rate 2) conversion to sinus rhythm – in highly symptomatic patients (BY TARGETING ECTOPIC FOCI/RE-ENTRY): - procainamide, flecainamide, amiodarone or sotalol

Question 42

What is the treatment of Ventricular Fibrillation?

Answer 42

irregular rhythm with uncoordinated contraction, IMMEDIATE CAUSE OF DEATH REQUIRES IMMEDIATE CARDIOVERSION: - ELECTRICAL: transthoracic defibrillation and/or - PHARMACOLOGICAL: IV amiodarone, lidocaine or magnesium may be used as an adjunct

Question 43

What is the treatment of Ventricular Tachycardia?

Answer 43

to terminate an episode - in patients unconscious and hypotensive (mean arterial pulse <60 mm Hg): cardioversion (synchronized DC shock) - in patients with stable hemodynamics: IV lidocaine, flecainide patients without structural heart disease), amiodarone, sotalol special cases - torsade de pointes: IV magnesium is the treatment of choice arrhythmias after acute myocardial infarction: IV lidocaine often used as a first line agent for chronic therapy of VT: - implantable cardioverter defibrillators (ICD) is preferred over antiarrhythmic drugs for initial therapy

Question 44

What are the Implantable Cardioverter Defibrillators (ICD) side effects?

Answer 44

- anxiety, depression, post-traumatic stress disorder (b/c shocks are uncomfortable) - amiodarone may be used in conjunction to reduce risk of ICD shocks *Electrical stimulus will disrupt activity & maintain a normal sinus rhythm