Lecture 5 - Antiarrhythmics 2 Flashcards
Bradyarrhythmias: HR = ?
< 50-60 bpm
Types of Bradyarrhythmias
- Sick sinus syndrome
- Atrio-ventricular conduction block
Tachyarrhythmias: HR = ?
> 100 bpm
Types of Tachyarrhythmias
- Supraventricular
- Ventricular
List and describe 3 types of Supraventricular arrhythmias
1) Paroxysmal Tachycardia: HR 150-250 bpm
2) Atrial Flutter: atria beat at 250-350 bpm, regular heart rhythm
3) Atrial Fibrillation: atria beat up to 500 bpm, irregular rhythm, uncoordinated contraction
List and describe 3 types of Ventricular arrhythmias
1) Ventricular Tachycardia: >120 bpm, regular heart rhythm
2) Ventricular Fibrillation: irregular rhythm with uncoordinated contraction, immediate cause of death
3) Torsade de pointes: long QT syndrome
What is an 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 most important ions in Pacemaker (slow) cells?
SA node, AV node
Ca2+
K+
What are the most important ions in Non-Pacemaker (fast) cells?
(atria, purkinje fibres, ventricles)
Na+
Ca2+
K+
List a few causes of cardiac arrhythmias
- Insufficient oxygen to myocardial cells
- Acidosis or accumulation of waste products
- Electrolyte disturbances
- Structural damage of the conduction pathway
- Drugs
What are the 2 mechanisms of cardiac arrhythmias?
1) Abnormal impulse formation
A) Abnormal automaticity
B) Triggered Activity
2) Abnormal conduction
Describe:
1A) Abnormal automaticity
- SA node (altered regular pacemaker activity)
- ectopic foci (pacemaker of abnormal origin)
- decrease in phase 4 K+ conductance (hypokalemia) - increases spontaneous depolarization
- inactivation of Na+ channels in depolarized cells (ischema) - converts fast cells into ectopic pacemakers
- localized super sensitivity to catecholamines following ischema
What would cause a change in phase 4 slope?
- increase rate of depolarization
- decrease rate of depolarization
increase rate of depolarization = ?
increased HR
decrease rate of depolarization
decreased HR
More depolarized RMP = ?
increased HR
More hyperpolarized RMP = ?
decreased HR
More negative AP threshold = ?
increased HR
More positive AP threshold = ?
decreased HR
SNS _______ HR
increases
PNS _______ HR
decreases
ACh is released from _____ nerves
parasympathetic
ACh acts on _____ receptors
muscarinic
How does ACh affect the heart?
- phase 4 - slows depolarization rate
- decreases automaticity (SA node)
- slows conduction (AV node)
NE/E is released from ______ nerves
sympathetic
NE/E acts on ______ receptors
B-adrenergic
How does NE/E affect the heart?
- phase 4 - increases depolarization rate and reduces AP firing threshold
- increases automaticity (SA node)
- increases conduction (AV node)
Describe:
1B) Triggered activity
-slow and poorly conducted action potential in atria or ventricle
- cells depolarize before complete repolarization has occurred
- non-automatic myocardial cells (atria, ventricles)
- repolarization is required to change Na channels from inactive to resting
- Ca channel availability is based on time
- may be caused by prolonged duration of action potential - prolonged QT interval?
- with increased action potential duration (QT interval) calcium channels may be ready before the sodium channels
EAD = ?
early after depolarization
EAD is due to ?
opening of Ca channels
EADs may trigger ________
Torsade de Pointes
Torsade de Pointes = ??
twisting of the points
Why type of conditions or drugs may precipitate Torsade de Pointes?
conditions or drugs which prolong the QT interval
Torsade de Pointes:
Characterized by ??
twisting of isoelectric points on ECG and prolonged QT interval
Torsade de Pointes:
Can be ____ or drug-induced
inherited
Torsade de Pointes:
Can lead to ??
ventricular fibrillation and sudden death
Torsade de Pointes:
Responds to _____
magnesium (Class 5 anti arrhythmic)
What drugs can increase QT interval?
- aniarrhythmics (Class 1a and 3)
- antihistamines
- anti-psychotics
- antibiotics (ex. erythromycin)
Describe:
2) Abnormal conduction
- impaired AV node (heart block) leads to bradyarrhythmias
- re-entry (circus) conduction leads to tachyarrhythmias
- local differences in conduction velocity and membrane characteristics lead to development of electrical circuits (circus conduction)
- re-routing of the normal electrical circuitry results in multiple beats before the next sinus beat is generated resulting in tachycardia
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)
See slides 20-22 about a unidirectional block
cool beans
List some causes of re-entry
- ischemia
- congenital
- hyperkalemia
Re-entry can occur in what parts of the heart?
In any part of the heart:
- AV node
- between SA node and atria
- between atria and ventricles
- accounts for most tachyarrhythmias in cardiac patients
How can re-entry be stopped?
by converting the unidirectional block tissue to bi-directional block
**In non-pacemaker (fast) cells, this can be done with drugs that block Na+ channels directly (Class 1 drugs)
A special case of re-entry in the AV node can cause what?
paroxysmal supra ventricular tachycardia (PSVT)
-cause is not clear and is often short lasting
Re-entry in the AV node is controlled by what kind of drugs?
Drugs that depress AV conduction, causing bidirectional block:
- calcium channel blockers (Class 4)
- B blockers (Class 2)
- Adenosine (Class 5)
In some cases an abnormal electrical pathway may be present. Ex. _______
wolff-parkinson-white syndrome
Describe 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
- Treated by catheter ablation of abnormal electrical pathway
- Amiodarone is first choice agent used to stabilize heart rate
______ = first first choice agent used to stabilize heart rate in Wolff-Parkinson-White syndrome
Amiodarone
When would you want to avoid AV node blockers?
If atrial fibrillation or flutter
-B blocker, Ca2+ blocker, adenosine or digoxin
What are the 3 mechanisms of action of antiarrhythmic drugs?
1) Reducing Automaticity
2) Blocking re-entry mechanisms
3) Normalizing ventricular rate (supraventricular tachycardia)
Describe ways we can reduce automaticity
1) blocking inactivated Na or Ca channels in depolarized tissues (preventing conversion to “resting” state)
- will reduce triggered activity
2) hyper polarize RMP (more negative RMP)
- will reduce pacemaker activity
3) increase membrane threshold potential for activation of NA (fast cells) of CA channels (slow cells)
- will reduce pacemaker activity
Describe ways we can block re-entry mechanisms
1) -Reduce phase 0 depolarization
- Slows conduction in the ischemia area
- Converts region of unidirectional block to bidirectional block
2) -Prolong the action potential repolarization
- Increases the effective refractory period (ERP)
- Conduction time < ERP = re-entry blocked
Describe how we can normalize ventricular rate (supraventricular tachycardia)
-slowing AV nodal conduction
(B blockers - Class 2)
(Ca blockers - Class 5)
(Digoxin)
- reduces ventricular rate
- increasing time for ventricular filling from atrium
- improves stroke volume (SV)
- increases cardiac output (CO = HR X increased SV)
- improved hemodynamics
Class 1 drugs block ___ channels
Na+
Examples of Class 1 drugs
procainamide
lidocaine
flecainide
Class 2 drugs block __
B receptors
Examples of Class 2 drugs
propranolol
metoprolol
esmolol
Class 3 drugs block __ channels
K+
Examples of Class 3 drugs
amiodarome
sotalol
Class 4 drugs block __ channels
Ca2+
Examples of Class 4 drugs
verapamil
Class 5 drugs have other mechanisms: Give some examples of class 5 drugs
magnesium
adenosine
digoxin
Describe Class 1A sodium channel blockers
Procainamide:
- Moderate phase 0 depression and slow conduction
- Usually prolong repolarization
Also blocks K+ channels in phase 3
- prolongs duration of action potential (QT interval)
- increases effective refractory period
slowed conduction + increased refractory = block reentry
Also decreases phase 4 slope = reduced automaticity of ectopic pacemakers (ventricular muscle and purkinje fibres)
Describe Class 1B sodium channel blockers
Lidocaine:
- Minimal phase 0 depression and slow conduction
- Usually shorten repolarization
- modest effect in normal tissue -especially atria because the AP duration is so short
- block is increased in depolarized tissue (ex. ischemic) - selective depression of conduction in depolarized cells
Describe Class 1C sodium channel blockers
Flecainide:
- Strong phase 0 depression and slow conduction
- Little effect on repolarization
- Modest K channel block but no increased QT interval
- Slight to no effect on the refractory period
Why is the use of procainamide limited?
- depresses hemodynamics
- blockade of K channels
- prolongation of QT interval
- may cause Torsade de points
- may cause Lupus like Syndrome
- reversible, occurs in1/3 of patients
- chronic treatment doesn’t appear to reduce mortality rate
Class 1B - Lidocaine:
Usually given __
IV
Class 1B - Lidocaine:
Has no value in treating _______ ________, due to lack of effect on the atria (because AP duration is too short)
supra ventricular tachyarrhythmias
Class 1B - Lidocaine:
Toxicity ?
- Low incidence of toxicity and hemodynamic side effects
- Neurologic effects: tremor, nausea, lightheadedness, hearing disturbances, slurred speech and convulsions
Class 1C - Flecainide:
Contraindicated in ??
patients with previous myocardial infarction, highly arrhythmogenic
Class 1C - Flecainide:
Used to treat what?
supra ventricular (atrial fibrillation and flutter) and life-threatening ventricular arrhythmias, particularly where benefits outweigh pro arrhythmic risk (life-threatening sustained VT) but only in patients with structurally normal hearts
_____ = non-specific B blocker
Propranolol
____ and ____ = B1 selective blockers
Metoprolol
Esmolol
B blockers ____ HR
decrease
How do B-blockers decrease HR?
- reduced phase 4 slope in pacemaker cells by reducing the pacemaker current (funny current - If)
- reduced AV conduction velocity by reducing the voltage-gated Ca2+ current
- prolonged refractory period in nodal tissues
B-blockers are mainly used to control ??
ventricular rate in supra ventricular tachycardias (atrial fibrillation and flutter)
B-blockers reduce short and long term mortality after ??
acute MIs
- counters increased sympathetic activity in patients with AMI
- anti-hypertensive and anti-ischemic effect is beneficial
Contraindications of B-blockers?
- bradycardia and heart block
- patients with pulmonary problems: cardioselective beta blockers may be used with caution, but non-selective B-blockers CI.
- decompensated congestive heart failure (due to negative inotropic effects)
- in diabetics, may mask tachycardia occurring with insulin-induced hypoglycaemia (risk of diabetic shock/coma)
- CI in Wolff-Parkinson-White Syndrome (may increase re-entry)
Because esmolol has a very short __________ it may be used inc cases where B-blockers would normally be CI.
duration of action (t1/2 = 10 min)
Describe:
Class 3 agents (amiodarone and sotalol)
- K+ channel blockade in phase 3 prolongs the cardiac AP duration (increased QT interval)
- increased refractory period
Describe Amiodarone (Class 3)
Wide Spectrum anti arrhythmic
- block inactivated Na channels (Class 1)
- block Ca channels (Class 4)
- modest B-blocker (Class 2)
Sotalol is also a _____
B-blocker
Class 3 agents (amiodarone and sotalol) are generally well tolerated hemodynamically, can be used in patients with ??
structural heart disease
Risk with Class 3 agents (amiodarone and sotalol) ?
by prolonging AP duration, they prolong QT interval - may predispose pt to torsade de pointes
Amiodarone is used for?
Both supra ventricular and ventricular tachycardia:
For supra ventricular tachycardia - maintains sinus rhythm in patients with recurrent atrial fibrillation
For ventricular tachycardia - effective, with less risk of pro-arrhythmic effect compared to other drugs
Shit ton of adverse effects with amiodarone - see slides 46 and 47
prob won’t but ok :)
Why kind of arrhythmias is sotalol effective against?
Supraventricular tachycardia (equally effective as amiodarone) - maintains sinus rhythm in patients with recurrent atrial fibrillation
Ventricular tachycardia: less effective than amiodarone, but may be preferred when amiodarone toxicity is a concern since it has fewer non-cardiac effects
Adverse effects of sotalol
- Excreted exclusively by kidneys - may accumulate in patients with renal disease
- Bradycardia (13%) - CI in patients with sick sinus syndrome
- Bronchospasm - due to non-selective block of B-blockers
- Greater risk of torsade de pointes than amiodarone (due to AP prolongation)
Describe Class 4 drug - Verapamil
- Blocks Ca channels in plasma membrane (open and inactivated)
- Slow conduction in AV node due to Ca channel blockade
- Used to reduce ventricular rate in supra-ventricular tachycardias (atrial fibrillation and flutter)
- Increased ventricular filling - increased CO
- Verapamil used in acute paroxysmal supra ventricular tachycardia (reentry through the AV node)
- CI in Wolff-Parkinson-White syndrome
Magnesium (Class 5) useful in ??
Torsade de Pointes, even when magnesium levels are normal - first-line agent
Where else is magnesium valuable in?
Ventricular arrhythmias in ischemic cells, associated with loss of cellular magnesium.
Describe the mechanism of magnesium
Mechanism unknown, but may involve regulating calcium accumulation
- reduces sodium and calcium currents
- reduces calcium release from the SR
- cofactor of the Na+/K+ ATPase pump
Very fucking briefly describe Adenosine (Class 5) - this lecture needs to END
-Acts on purine (A1) receptors of SA and AV nodes
Mode of action:
- increases K+ conductance (hyperpolarizes)
- depresses slow inward Ca2+ current
- slows the phase 4 of AV pacemaker action potential
- slows sinus rate and decreases AV node conduction
- used for supra ventricular tachycardia due to AV node re-entry
kay sorry that wasn’t that brief
Adenosine is given ___
IV
Drug interactions with Adenosine ?
methylxanthines (caffeine/theophylline) block adenosine receptors
Describe Digoxin (Class 5)
- decreases AV node conduction
- simulates vagus nerve and releases ACh
- inhibits calcium currents and activates K+ currents
- useful in atrial fibrillation, atrial flutter, and supra ventricular tachycardia with a rapid ventricular response
- reduces the ventricular rate - increases stroke volume - increases CO
- can lead to delayed afterdepolarizations
- should not be used in wolf-parkinson-white syndrome - may cause death
Treatment of bradycardia
symptomatic bradycardia (<50-60 bpm) = pacemaker
Treatment of tachycardia
- isolated ectopic beats or short runs of tachycardia
- if asymptomatic - no treatment
-symptomatic/severe tachycardia - immediate cardioversion (electrical/pharmacological)
Treatment of paroxysmal tachycardia
- vagal maneuvers (valsalva, carotid massage)
- IV adenosine or verapamil or beta-blockers; target AV node to reduce ventricular rate
For WPW: has to be treated with procainamide, flecainide or amiodarone
If area of tissue responsible for the arrhythmia can be identified (ectopic site, accessory pathway), then radio frequency ablation is preferred: highly effective, life-long cure. Avoids unwanted side effects of arrhythmic drugs
How do you treat atrial fibrillation?
- anticoagulation
- antiarrhythmics:
1) ventricular rate control
2) maintain sinus rhythm
1) Rate control:
- Verapamil, beta-blocker, digoxin; target AV node to reduce ventricular rate
- Amiodarone
2) Rhythm control - in highly symptomatic patients:
- Procainamide, flecainamide, amiodarone or sotalol
How do you treat ventricular fibrillation?
Irregular rhythm with uncoordinated contraction, immediate cause of death
- transthroacic defribrillation - IV amiodarone, lidocaine or magnesium may be used as an adjunct
How do you treat ventricular tachycardia to terminate an episode
In patients unconscious and hypotensive (mean arterial pulse <60 mmHG): cardioversion (synchronized DC shock)
In patients with stable hemodynamics: IV lidocaine, flecainide patients without structural heart disease), amiodarone, sotalol
How do you treat ventricular tachycardia (special cases)
Torsade de pointes: IV magnesium is the treatment of choice
-Arrhythmias after acute MI: IV lidocaine often used as a first line agent
How do you treat ventricular tachycardia (for chronic therapy for VT)
implantable cardioverter defibrillators (ICD) is preferred over anti arrhythmic drugs for initial therapy
Side effects of implantable cardioverter defibrillators (ICD)?
- anxiety, depression, post-traumatic stress disorder
- amiodarone may be used in conjunction to reduce risk of ICD shocks
