Antiarrhythmic Drugs (part 2) Flashcards
Arrhythmia =
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
Bradyarrhythmias:
HR < 50-60 bpm
- Sick sinus syndrome
- Atrio-ventricular conduction block
Tachyarrhythmias:
HR > 100 bpm
Supraventricular tachyarrhythmias
due to abnormal electrical signals originating above the ventricles
Paroxysmal tachycardia :
HR 150-250 bpm
Atrial Flutter:
atria beat at 250-350 bpm, regular heart rhythm
Atrial Fibrillation:
atria beat up to 500 bpm, irregular rhythm, uncoordinated contraction
Ventricular tachyarrhythmias
due to abnormal electrical signal originating in ventricles
Ventricular Tachycardia:
> 120 bpm, regular heart rhythm
Ventricular Fibrillation:
irregular rhythm with uncoordinated contraction, immediate cause of death
Arrhythmia caused by:
Alteration in the movement of ions responsible for the action potentials in the pacemaker cells, conduction system and/or muscle.
What are the important ions in the action potential?
- Pacemaker (slow) cells (SA node, AV node)
- Ca and K are most important. - Conduction and muscle (fast) cells (atria, purkinje fibers, ventricles)
- Na, Ca and K are most important
What are the causes of cardiac arrhythmias?
- 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)
What are the mechanisms of cardiac arrhythmias?
- 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
- disturbances in repolarization triggers EARLY AFTERDEPOLARIZATIONS (EADs) in ATRIA or VENTRICLES
- Abnormal conduction
- impaired AV node (heart block) leads to bradyarrhythmias
- RE-ENTRY (circus) conduction leads to tachyarrhythmias
Describe where ACh is
- neurotransmitter
- released from parasympathetic nerves
- acts on muscarinic receptors
phase 4 - slows depolarization rate
- decreases automaticity (SA node),
- slowed conduction (AV node)
Describe where Norepinephrine/Epinephrine is
- 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)
What may trigger Torsade de pointes?
Early Afterdepolarizations (EADs)
What is Torsade de pointes?
twisting of the points (looks like a party streamer)
conditions/drugs which PROLONG the QT interval may precipitate these
Torsade de pointes
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
What do drug induced increase in QT interval include?
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
What does re-entry require?
- available circuit (closed conduction loop)
- unidirectional block
- different conduction speed in limbs of circuit: conduction time (CT) > effective refractory period (ERP)
Where does re-entry occur?
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
What happens when re-entry is localized to atria/ventricles?
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)
A special case of reentry in the AV node:
- paroxysmal supraventricular tachycardia (PSVT)
– cause not clear and is often short lasting
What is the re-entry in the AV node (special case) controlled by?
controlled by drugs that depress AV conduction, causing bidirectional block
- calcium channel blockers (Class IV)
- β-adrenergic receptor blockers (Class II)
- Adenosine (Class V)
Wolff-Parkinson-White Syndrome
in some cases an abnormal electrical pathway connecting the atria and ventricles may be present
What is Wolff-Parkinson-White Syndrome?
- 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
What should you avoid if patient has Wolff-Parkinson-White Syndrome?
Avoid AV node blockers if atrial fibrillation or flutter
- β-adrenergic receptor blocker , calcium antagonist, adenosine or digoxin
What are the Mechanisms of Action of Antiarrhythmic Drugs?
- Reducing Automaticity
- Blocking Re-entry Mechanisms
- Normalize Ventricular Rate (SUPRA-VENTRICULAR tachycardia)
–> by slowing conduction through the AV node
Mechanisms of Action of Antiarrhythmic Drugs
1) Reducing Automaticity
A) Abnormal automaticity
B) Triggered activity
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
Mechanisms of Action of Antiarrhythmic Drugs
2) Blocking Re-entry Mechanisms
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
Mechanisms of Action of Antiarrhythmic Drugs
3) Normalize Ventricular Rate (SUPRA-VENTRICULAR tachycardia)
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
What are the Class I antiarrhythmia drugs?
(procainamide, lidocaine, flecainide)
- primarily block Na channels
What are the Class II antiarrhythmia drugs?
(propranolol, metoprolol, esmolol)
- primarily block B-adrenergic receptors
What are the Class III antiarrhythmia drugs?
(amiodarone, sotalol)
- primarily block K channels
What are the Class IV antiarrhythmia drugs?
(verapamil)
- primarily block Ca channels
What are the Class V antiarrhythmia drugs?
(magnesium, adenosine, digoxin)
- other mechanisms
What are the 3 subclasses of Na+ channel blockers?
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
What is the treatment of Bradycardia?
symptomatic bradycardia (< 50-60 bpm) – PACEMAKER
What is the treatment of Tachycardia?
- isolated ectopic beats or short runs of tachycardia
– if Asymptomatic - no treatment - Symptomatic/severe tachycardia – IMMEDIATE CARDIOVERSION (ELECTRICAL/PHARMACOLOGICAL)
What is the treatment of Atrial Fibrillation?
- 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
What is the treatment of Ventricular Fibrillation?
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
What is the treatment of Ventricular Tachycardia?
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
What are the Implantable Cardioverter Defibrillators (ICD) side effects?
- 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
