Antiarrhythmic Flashcards
1
Q
What are the various classes of anti-arrhythmics?
A
a. Class I: Fast Sodium Channel Blockers
b. Class II: Beta-Adrenergic Antagonists
c. Class III: Inhibitors of Repolarization
d. Class IV: Calcium Channel Blockers
e. Other: (adenosine, digitalis, etc.)
2
Q
Conduction system of the heart?
A
- Sinoatrial (SA) node
- Atria- pauses at AV node
- Atrioventricular (AV) node
- Bundle of His
- Bundle Branches
- Purkinje fibers
- Ventricles
3
Q
What is the action potential in cardiac myocytes?
A
-
Phase 0 rapid depolarization - (-60 is threshold with all or nothing depolarization)
- fast sodium channels open;
- fast inward flow of Na+;
- closing K+ channels )
-
Phase 1 begin repolarization
- sodium channels close
- K+ channels open
-
Phase 2 plateau (where class II antiarrhythmics work and Class Iv (CCB))
- slow calcium channels open
- slow inward flow of Ca2+
-
Phase 3 repolarization (Where Class III antiarrhtyhmics work)
- calcium channels close
- potassium channels open
- slow outward K+ current
-
Phase 4 pacemaker potential; return to resting membrane potentials
- combo increased inward current and decreased outward current
- occurs most rapidly in SA node, but all myocardial cells capable
- Refractory period (phases 1-3) (periods of repolarization)
4
Q
What occurs during NSR?
A
- Sinoatrial node is cardiac pacemaker
- Normal sinus rhythm 60-100 beats/min
- Depolarization triggers depolarization of atrial myocardium
- Conducts more slowly through AV node
- Conducts rapidly through His bundles and Purkinje fibers
5
Q
What occurs during SA/AV node action potential?
A
Phase 0- Ca is major ion causing depolarization at the nodes (Na in myocytes)- kinetics of Ca is slower than Na
- upstroke
- Critical firing threshold (-40mV)
- Slower and Ca2+ mediated
Phase 3
- Repolarization
- Inactivation of Ca2+ and Na+ channels
- Activation of K+ channels
Phase 4
- Gradual depolarization
- Slow inward Na+ (If funny current) and Ca2+ currents
6
Q
What is the effect of SNS and PSNS on SA node?
A
- SA Node rate controlled by autonomic nervous system
- Sympathetic system stimulation
- (ß1 receptors activated)
- Increases catecholamines
- Increased heart rate (positive chronotropic effect)
- Increased automaticity
- Facilitation of conduction of AV node
- Parasympathetic system predominates- at rest, vagal tone of PSNS
- (M2 muscarinic receptors)
- Decreases heart rate
- Inhibits AV conduction
- Reduced automacity
7
Q
How are arrhythmias classified?
A
- An arrhythmia is a disturbance in the electrical activity of the heart
- Classified according to:
- Site of origin of abnormality (atrial/ junctional / ventricular)
- Complexes on ECG (narrow/broad)
- Heart rhythm (regular/irregular)
- Heart rate is increased or decreased
8
Q
Mechanism of Arrhythmia Production?
A
-
Altered automaticity - latent pacemaker cells take over the SA node’s role; escape beats (ectopic)
-
caused by excessive SNS activity (ie epinephrine bolus)
- increase stage 4 depolarization in cells other than SA node
- ischemic cell can take over as pacemaker
-
caused by excessive SNS activity (ie epinephrine bolus)
-
Delayed after-depolarization - normal action potential of cardiac cell triggers a train of abnormal depolarizations
-
main cause is high calcium levels, triggering inward current and train abnormal AP
- Too much Ca, activated Na/Ca exchanger (1 Ca outward and 3 Na inward- net charge 1)–> reach threshold and inappropratie firing
- Also hypokalemia, and prolonged QT interval
-
main cause is high calcium levels, triggering inward current and train abnormal AP
-
Re-entry - refractory tissue reactivated repeatedly and rapidly due to unidirectional block, which causes abnormal continuous circuit
- abnormal tissue, WPW,- abnormal conduciton pathway
- infarction- dead myocardial tissue that doesn’t conduct impulse and impulses have to travel around it
-
Conduction block – impulse fail to propagate in non-conducting tissue
- fibrosis, ischemic damage to conducting system
9
Q
Factors that can underlie cardiac arrhythmias?
A
- Arterial hypoxemia
- Electrolyte imbalance
- Acid-base abnormalities
- Myocardial ischemia
- Altered sympathetic nervous system activity
- Bradycardia
- Administration of certain drugs
- Enlargement of a failing ventricle
10
Q
When do we treat arrhythmias?
A
- They cannot be corrected by the removing the precipitating cause
- Hemodynamic function is compromised
- The disturbance predisposes to more serious cardiac arrhythmias or co-morbidities
11
Q
Management of arrhythmias?
A
- Acute management (clinical assessment of patient and diagnosis)
- Chronic treatment
- Prophylaxis treatment
- Non-pharmacological (vagal maneuver, cardioversion, reentry- RFCA of pathway, defibrillators)
- Pharmacological (some antiarrhythmic drugs are also proarrhythmic)
12
Q
Non pharmacologicla treatment of arrhythmias?
A
- Acute
- Vagal maneuvers
- Cardioversion
- Prophylaxis
- Radiofrequency catheter ablation
- Implantable defibrillator
- Pacing (external, temporary, permanent)
13
Q
What are the Vaughan Williams Classification of Antiarrhythmic drugs?
A
- Class I: Sodium channel blockers
- Ia- ex disopyramide - Na-channel block intermediate dissociation
- Ib- lidocaine- Na channel block fast dissociation
- Ic- Flecainide- sodium channel block slow dissociation
- Class II: Beta adrenergic blockers
- Class III: Potassium channel blockers
- Class IV: Calcium channel blockers
- Class V: Unclassified drugs
14
Q
What are some drugs unclassified in Vuaghan Williams system?
A
- Atropine
- Adrenaline (epinephrine)
- isoprenaline (isoproteronol)
- digoxin
- adenosine
- Calcium cholorid
- Magnesium chloride
15
Q
What is MOA of Class I antiarrhythmic agents?
A
- Block sodium channels
- Blocks inward sodium ion flow during depolarization which will slow conduction rate and result in suppression of the maximum upstroke velocity (V max) of the cardiac action potential
- bind alpha subunit on sodium channel
- bind more strongly in open, inactivated state
- lidocaine binds preferentially inactivated state
- do not bind readily in rested state
- “use dependent block”
- Slows conduction
- Depresses Phase 0
16
Q
MOA Class IA agents? Examples?
A
- Intermediate Na+ channel blocker (intermediate dissociation)
- Decrease depolarization rate (phase 0)
- Slows conduction velocity
- Increase refractory period (prolonged repolarization)
- Increase AP duration
- Decreased automaticity
- Examples:(more historical)
- Quinidine –Not currently available in US
- Procainamide
- Disopyramide
17
Q
What is procainamide use? dose? s/e?
A
- Class IA
- Used in the treatment of ventricular tachyarrhythmias (less effective with atrial)
- Dose: Loading 100 mg every 5 minutes until rate controlled (max 15 mg/kg); then infusion 2-6 mg/min
- Side effects:
- Myocardial depression leading to hypotension
- Sydrome that resembles lupus erythematosus
18
Q
What is disopyramide? uses? s/e?
A
- Class Ia
- Used in the treatment of both atrial and ventricular tachyarrhythmias
- Oral agent
- Side effects:
- Significant myocardial depressant effects
- Anticholinergic effects, which result in blurred vision, dry mouth, constipation, and urinary retention
- off target effect, independent Na chanel
19
Q
What are class IB agents? their effects? examples?
A
Fast Na+ channel blocker (fast dissociation)
- Decreases AP duration
- Decreases effective refractory period
- Produces little effect on maximum velocity depolarization rate
- because fast dissociation
- Decreases automaticity (particularly in ectopic ischemic cells)
- useful for ischemic myocytes
- preferentially block cells ifring rapidly and leave normal sinus rhythm intact
- bind selectively to inactivated channels and associate/dissociate very quickly
- Examples:
- Lidocaine - Class IB Prototype
- Mexiletine
- Tocainide
- Phenytoin
20
Q
Lidocaine class? Use?
A
- Class IB antiarrhythmic
- Used in the treatment of ventricular arrhythmias
- Used in acute treatment of ventricular dysrhythmias in immediate aftermath of MI (Rang & Dale, 7th ed. p 256)
- Is no longer recommended for preventing ventricular fibrillation after acute MI (Stoelting, 8th ed. P. 523)
- Particularly effective in suppression reentry rhythms: ventricular tachycardia, fibrillation, PVCs
21
Q
Lidocaine dose, max dose? metabolism?
A
- Dose: 2 mg/kg IV, infusion 1-4 mg/min
- (max dose 3 mg/kg)
- Therapeutic plasma concentration 1-5 ug/mL
- Hepatic metabolism
- Active metabolite with antiarrhythmic activity
- Metabolism may be impaired by drugs such as cimetidine and propanolol, or physiologic altering conditions such CHF, acute MI, liver dysfunctioin, GA; or can be induced by drugs like barbiturates, phenytoin, or rifampin
- dependent on hepatic blood flow for metabolism
22
Q
Lidocaine adverse effects
A
- hypotension
- bradycardia
- seizures- inhibiting the inhibitors
- CNS depression
- drowsiness, dizziness
- lightheadedness
- tinnitus
- confusion
- apnea,
- myocardial depression,
- sinus arrest, heart block
- ventilatory depression
- cardiac arrest
- can augment preexisting neuromuscular blockade
29
Q
What are Class II agents MOA? Use? Examples?
A
MOA
- Beta-adrenergic antagonists.
- Decrease rate of spontaneous phase 4 depolarization resulting in decreased SA node discharge and decreased autonomic nervous system activity
- Decreased conduction velocity
- Decreased automaticity
-
Example:
- Propanolol – Prototype
- Metoprolol
- Esmolol
- Labetolol (off-label use)
USE:
- Used in treatment of SVT, atrial and ventricular arrhythmias
- Used in treatment ventricular dysrhythmias during MI and reperfusion
- Prevents catecholamine binding to beta receptors
- Slows of heart rate
- Decreases myocardial oxygen requirements
35
Q
Class III agents?
A
- Block potassium ion channels (impact on phase 3 of AP)
- Results in prolongation of cardiac repolarization by increasing the duration of the cardiac action potential and the effective refractory period, which results in prolongation of the QTc interval on ECG
- can promote polymorphic VT and torsades, especially when combines with other QT prolongaters
44
Q
MOA Class IV agents? Examples?
A
-
Block slow calcium channels
- cardiac selective ones like verapamil are mostly used here
- *primary site AV node- helps to slow heart rate
- Blocks slow calcium channels, which decreases conduction through AV node (block sponatenous phase 4 depolarization and decrease rate of rise in phase 0 in AV node) and shortens Phase 2 (the plateau) of the action potential in ventricular myocytes
- Contractility of the heart decreases
Examples:
- Verapamil – Class IV Prototype
- Diltiazem *
