Anti-Arrhythmics Flashcards
Phases of cardiac potential: how many phases? What are they called?
Five phases from 0 - 4
0- rapid depolarisation 1- initial repolarization 2- plateau phase 3- repolarization 4- resting potential
What happens in Phase 0?
Results from rapid influx of Na+
Depolarisation raises resting membrane potential from -85mV to +20mV. At this point threshold potential has been reached and an all or none action potential response occurs.
Rapid influx Na+ raises membrane potential further to 20mV.
What happens in Phase 1?
Initial repolarization:
Voltage gated Na channels close as transmembrane potential becomes sufficiently positive.
Notch caused by transient outward K+ and inward Cl- movement.
What happens in Phase 2?
Inward movement of Ca+ ions through slow L-type Ca channels,
and outward movements of K+.
Cancel out each other, and only slow downward slope to repolarisation.
What happens in Phase 3?
Repolarization as calcium efflux slows/stops and
K+ movement out via concentration gradient via open K+ channels.
Relative refractory period.
What happens phase 3-4?
Resting membrane potential is re-established by 2K+ moving inwards for every 3Na+ outwards
Gives a net outward movement of positive charge.
Mechanisms of Arrhythmia generation (4)?
- Enhanced automaticity
- Abnormal automaticity
- Triggered activity
- Re-entry (circus movement)
what arrhythmias occur with
- enhanced normal automaticity
- Abnormal automaticity
- Triggered activity
- Inappropriate sinus tachycardia, by phase 4 depolarisation.
- Ectopic atrial tachycardia by phase 4 depolarisation
- Torsades de pointes- action potential duration/ early afterdepolarisation
Digixon induced arrhythmia- calcium over load or delayed afterdepolarization.
What are the re-entry arrhythmias?
Atrial flutter type 1- conduction and excitability
Wolf Parkinson White - conduction and excitability
Ventricular fibrillation - refractory period vulnerable
How many phases of cardiac cycle do pacemaker cells have?
3 phases, - 0, 4 and 3
How is resting membrane potential re-established?
- the resting membrane potential is re-established by 2K+ in and 3Na+ out.
What classification does The Vaughan-Williams Classification Scheme?
5 classes with class 1 (a, b, c) 1- Na channel blockers (fast, intermediate, slow) 2- B blockers 3- K channel blockers 4- Ca channel blockers 5- work by unknown mechanism
How do Vaughan-Williams Class I work?
Provide examples of the subclasses, effect on action duration and effective refractory period and clinical uses.
Drugs reduce the phase 0 slope and the peak of the action potential - decrease membrane excitability and conduction velocity.
a - quinidine, procainamide. (increase ADP + ERP) (AF/SVT)
b - lidocaine (reduced ADP + ERP) (Dig Toxicity/ VF)
c - flecainide (no change) (AF/SVT)
Propranolol also has some Class 1 action.
Side effects of Na channel blockers?
CVS side effects - hypotension, bradycardia, arrhythmia
CNS side effects- Two phases: excitatory phase followed by depressive phase with increasingly heavier exposure.
- Nervous, anxiety, tremor, dizziness, hallucinations, seizures, psychosis, euphoria
- Drowsy, lethargic, slurred speech, confusion, LOC, respiratory depression
Contraindications to Na channel blocker?
- Syndromes:
Adam Stokes syndrome
Wolf Parkinsons White - Conduction defects:
2/3 heart block
Serious SA node block without pacemaker - Meds:
Prior use of amiodarone
Use of other Class 1 antiarrhythmics
Flecainide:
Uses
Side effects
Avoided?
Use: pill in the pocket to terminate AF, treatment of supraventricular tachycardias (inc those in WPW)
Side effects: arrhythmias (Torsades de Pointes), prolonged PR, widened QRS, can be negatively ionotropic effect
Avoid- structural heart diseases
Mechanism of B-blocker activity
Decreases sympathetic activity on the heart by acting as antagonists at b-receptors (antagonising catecholamines).
Prolongs Phase 4 ‘diastolic’ depolarization.
reduces intracellular cAMP levels and therefore reduces Ca influx. Produce bradycardia, depress myocardial contractility, prolong AV conduction.
Useful in treating supraventricular tachycardias.
Side effects of B-blockers
Hypotension Bradycardia Heart block Depression Sexual dysfunction Impaired glucose handling
Mechanism of K+ channel blockers
Prolong repolarization by blocking potassium channels, K+ efflux in Phase 3.
- > prolongs action potential duration and effective refractory period
- > bradycardia
Amiodarone:
Uses
Side effects
Contraindications
Uses- treatment of ventricular and supraventricular tachycardias, WPW
Increases APD, ERP
Side effects: interstitial lung disease, thyroid dysfunction (hypo/hyper), abnormal liver enzymes, corneal micro deposits and photosensitivity
Contra- pregnancy, bradycardia,
Mechanism of the Ca channel blocker?
Contra-indications
Side effects
- prevents influx of Ca through slow L-type channels in the AV and SA node, slowing conduction and automaticity.
- This shortens phase 2 - plateau of cardiac potential.
- Reduce contractility of the heart.
Contraindication: Should not be used in WPW- precipitate VT.
Side effects: constipation, dizziness, headache, redness on the face, ankle oedema, bradycardia
Adenosine mechanism action?
What arrhythmias can it be used to differentiate?
AV node block via specific adenosine-A receptors.
Short half life, less than 10 seconds - taken up rapidly by red blood cells.
Can be used to differentiate between VT and SVT. Will only treat SVT.
Adenosine side effects and contraindications.
Side effects: diaphoresis, metallic taste, nausea, sense of impending doom.
Contra-indications: asthma, decompensated heart failure, long QT syndrome.
Digoxin mechanism of action
Commonly used for rate control in AF
Action is to inhibit Na/K ATPase in the myocardium. Raises Na intracellular levels - eventually raises Ca and therefore prolongs phase 4 and phase 0 of the cardiac potential.
Also indirectly increases acetylcholine at cardiac muscarinic receptors. Slows conduction and prolonging the refractory period in the AV node and bundle of His.
Weak ionotrope.
Digoxin side effects
Narrow therapeutic index
- gynaecomastia, nausea, yellow vision.
- Hypokalaemia can precipitate side effects as both act at same cardiac receptors.
ECG changes in Digoxin toxicity
ST depression
Flat T waves
QT interval shortening
“Reverse tick sign”
Name some Class 1 anti-arrhythmias.
A- quinidine, procainamide (intermediated assoc/ dissoc)
B- lidocaine, phenytoin (fast assoc)
C- flecainide, propafenone (slow assoc)
Name class 2 antiarrhythmics
Beta blockers
Propranolol
Metoprolol
Name some class 3 antiarrhythmics
K channel blockers
Amiodarone - class 1-4 activity Sotalol - also Bblocker
Name some class 5 antiarrhythmics
Adenosine and Digoxin
- unknown mechanism
Lidocaine is contraindicated in which syndrome?
Wolf Parkinson White
What type of blockade happens in Class 1?
Sodium channel block.
Phase 0 prolonged
Increased effective refractory period.
Slows down HR
Good for SVT - AF, WPW tachy
Class 2 antiarrhythmics mechanism?
Ion target
Phase target
Reduced sympathetic stimulation of heart by blocking B-adrenegeric receptors.
Decreases Phase 4 nodal slope (Na/ Ca slow channel slope)
Class 3 antiarrhythmics:
Target ion block
Phase block
Effect on action potential
Potassium channel block,
Phase 3 of cardiac myocytes action potential
Prolongs ERP AND QT interval
Contraindicated in long QT syndromes- can trigger VF and VT
