11. Anti-arrhythmic Drugs Flashcards
What are the 2 goals of treatment for arrhythmia?
What are the 4 classes of mechanisms?
2 goals:
- Termination of an ongoing arrhythmia
- Prevention of an arrhythmia
4 classes: Class 1- Na channel blockers Class 2- Beta blockers Class 3- K channel blockers Class 4- Ca channel blockers
Can anti-arrhythmic drugs cause arrhythmias too?
Yes with long term use
The function of the heart depends on its electrical activity- mediated by the action potential
The action potential depends on the activity of ion channels: Na ion channels, K ion channels, Ca ion channels
Anti-arrhythmic drugs alter activity of ion channels (if incorrectly used they can cause arrhythmias)
Review the heart diagram slide 6-7 Anti-arrhythmic drugs
Okay
What are the 2 types of cardiac tissue?
- That with which action potentials occur automatically
- SA node (60-100bpm)
- AV node (50-60bpm)
- bundle of His (50-60bpm)
- purkinje system (30-40bpm) - That with which actions potentials do not occur automatically (received from automatic tissues and spread throughout)
- atrial muscle
- ventricular muscle
What are the 3 phases of the pacemaker action potential?
SA node AP
Phase 4- spontaneous If current- non-selective action channels (If current)- mainly carry Na in
Phase 0- rapid depolarization - inward Ca L type channels
Phase 3- repolarization - outward K current
Slide 9 anti-arrhythmic drugs
What are the 5 phases of action potential of cardiac myocytes?
Phase 0- rapid depolarization - inward Na - Ina current determines velocity if impulse conduction throughout ventricle
Phase 1- transient outward K current
Phase 2- (plateau) inward Ca current
Phase 3- repolarization - outward K current
(Phases 2/3 determine duration of AP and refractory period
Phase 4- resting phase, Na channels enter resting state from inactivated state
Slide 10 Anti-arrhythmic drugs
What are the 3 differences between pacemaker cells (SA node, AV node) and myocitic cells (atrial and ventricular muscle cells)?
- Pacemaker cells have automaticity (membrane starts to depolarizes slowly but spontaneously) while myocytes have no automaticity (membrane depolarizes when it receives AP from pacemakers)
- Pacemaker action potential has 3 phases, myocytes has 5 phases
- In pacemakers, Ca causes rapid depolarization in phase 0, in myocytes, Na causes rapid depolarization in phase 0
Slide 11 Anti-arrhythmic drugs
What is the serum K+ physiologic range?
What values are hypokalemic?
What values are hyperkalemic?
Serum K+ physiological range: 3.5 to 5 mM
Hypokalemia (<3.5mM)
Hyperkalemia (>5mM)
Both arrhythmogenic
What is hypokalemia?
How can they cause arrhythmias?
Serum K range of <3.5mM
Slows repolarization
Action potentials become wider (increased duration)
Cause arrhythmias by decreasing conductance of K channels, slow repolarization, K channel pores are blocked by Mg and polyamines, increase Na and Ca cause early and delayed after depolarizations, ectopic beats, ventricular tachycardia and fibrillation
Slides 12-14 anti-arrhythmic drugs
How can diuretics cause arrhythmias?
Diuretics (thiazides and loop) can cause hypokalemia and predispose to arrhythmias
What is hyperkalemia?
Serum K range of >5mM
Depolarizes membrane and slows conduction velocity
Renal failure can cause hyperkalemia and life threatening arrhythmias
Hyperkalemia decreases resting membrane potential (becomes more positive-depolarized)
Increases K channel conductance, faster repolarization
Decreases availability of Na channels responsible for phase 0 depolarization
At very high levels of K > 14mM conduction finals leading to cardiac arrest
Slides 15-16 anti-arrhythmic drugs
What are the effects of class 1 anti-arrhythmic drugs? Na channel blockers
Block Na channels in the open or inactive state
Decrease re entry and prevent arrhythmia
In atrial and ventricular muscle:
Decrease depolarization in phase 0, decrease conduction velocity
In SA node:
- decrease spontaneous Na channel opening in phase 4, decrease heart rate and automaticity
Slide 18 anti-arrhythmic drugs
Slide 27 AAD
What is class IA of Na channel blockers?
Uses?
Adverse effects?
IA- procainamide: class IA sodium channel blocker that prefers binding to open state
Used to treat supraventricular and ventricular arrhythmias (ex: atrial fibrillation)
Adverse effects: chronic treatment may cause lupus like syndrome
What is class IB of Na channel blockers?
Uses?
Adverse effects?
Lidocaine
Exhibits use dependant block (blocks Na channels in their open and inactive states)
Works best in depolarized or rapidly driven tissues (found in ischemic myocardium)
Also has local anesthetic action
Adverse effects: tremor, dysarthria, confusion, dizziness, seizures (due to block of CNS Na channels)
Used for acute IV treatment of ventricular arrhythmias. NOT useful in atrial arrhythmias
(Don’t think I have to know this use)
Slides 29-30 AAD
What are the common therapeutic effects of Na channel blockers? Who are class I drugs restricted to?
To treat supraventricular and ventricular arrhythmias (atrial flutter or fibrillation) and maintain sinus rhythm
To prevent ventricular tachycardia and fibrillation
Class I drugs restricted to patients with structurally normal hearts (can cause arrhythmias I’m not normal hearts)
Slide 31 AAD
What are the effects of class 2 anti-arrhythmic drugs? β blockers
Block β1 and β2 receptors in heart
In SA, AV nodes:
- decrease spontaneous Na channel opening in phase 4, decrease heart rate
- decrease Ca channel opening and depolarization in phase 0, decrease automaticity and conduction velocity at AV node
In ventricular muscle:
- decrease contractility (different mechanism)
Slide 19 AAD
Slide 32 AAD
What are the therapeutic uses of β blockers?
(4 of them)
Adverse effects?
Widely used, decrease mortality after myocardial infarction
Terminate re-entry arrhythmias involving AV node
Control the ventricular rate in atrial flutter and fibrillation
To suppress stress induced arrhythmias
Control arrhythmias induced by Na channel blockers
Adverse effects: can cause severe bradycardia and even AV block
What are the effects of class 3 anti-arrhythmic drugs? K channel blockers Adverse effects?
Block K channels
In atrial and ventricular muscle:
- decrease repolarization in phases 2 and 3, increase action potential duration (wider), increase refractory period, decrease re entry, prolonged repolarization
No effect in SA node
Adverse effects: increased risk of early after hyperpolarizations and torsades de pointes
Slide 20 AAD
Slide 34 AAD
What is the K channel blocker Amiodarone?
Adverse effects?
Blocks K channels, inactivated Na channels, Ca channels, and β receptors
Increases action potential duration, decreases conduction velocity, increases refractoriness in all cardiac tissues
Used for recurrent ventricular tachycardia or fibrillation resistant to other drugs
Adverse effects: (with higher doses and long term therapy) pneumonitis, pulmonary fibrosis, hyper or hypothyroidism
Slide 35 AAD
What is the K channel blocker sotalol?
Adverse effects?
Blocks K channels in all cardiac tissue (increases action potential duration)
Blocks β channels (decrease automaticity, decrease AV conduction, increase AV refractory period)
Used for ventricular tachyarrhythmias, atrial flutter and fibrillation
Adverse effects: fatigue, bradycardia, risk of torsades de pointes (with high dose and low plasma K)
Slide 36 AAD
What are the effects of class 4 anti-arrhythmic drugs? Ca channel blockers
Block L TYPE calcium channels in the heart
In AV node:
- decrease Ca channel opening and depolarization in phase 0, decrease automaticity and conduction velocity at AV node
In SA node:
- decrease depolarization in phase 0, decrease heart rate
Slide 21 AAD
What are the uses and adverse effects of Ca channel blockers?
Uses: supraventricular tachyarrhythmias, AV re-entrant tachycardia, decrease ventricular rate in atrial flutter and fibrillation, parental verapamil and diltiazem for rapid conversion of PSVTs to sinus rhythm
Adverse effects: bradycardia or AV block, hypotension, constipation
Do not combine non-DHPs with β blocker (can precipitate heart failure)
Slide 40 AAD
What are the 6 causes of arrhythmias?
- Defects in impulse formation- increase sympathetic or parasympathetic activity
- Electrolyte disturbances- hypo or hyperkalemia
- Drugs that increase action potential duration (decrease K currents, EADs, and DADs)
- Defects in impulse conduction- re entry, conduction block
- Damage to myocytes- myocardial infraction (mostly ventricular tachycardia and fibrillation)
- Structural defects
What are the 5 types of arrhythmias?
- Sinus tachycardia- SA node rate 100-180bpm
- Paroxysmal supraventricular tachycardia (PSVT)- atrial rate 140-250bpm
- Atrial flutter- atrial rate 280-300bpm
- Atrial or ventricular fibrillation- rate >300bpm
Atrial fibrillation can be fine for many years
Ventricular fibrillation is emergency - Torsades de Pointes (twisting of points around the baseline in an ECG)- results from after depolarizations when action potential duration is increased (some have prolonged QT syndrome) - slide 37-38 AAD
