Pharma treatment of dysrhythmias Flashcards
Discuss the underlying physiology of dysrhythmia
Underlying Physiology
Dysrhythmia (arrhythmia) describes conditions where the co-ordinated sequence of electrical activity in the heart is disrupted
This could be due to:
• Changes in the heart cells (ectopic pacemaker)
• Changes in the conduction of the impulse through the heart
• Combinations of these
Discuss the classifications of dysrhythmia
Dysrhythmias (arrhythmias) are broadly classified as:
• Atrial (supraventricular)
• Junctional (associated with the AV node)
• Ventricular
Three above are the site of the origin of the abnormality
• Tachycardia or bradycardias
What are the general classifications of dysrhythmia by event
Dysrhythmias (arrhythmias) arise from four broad categories of event: • Ectopic pacemaker activity • Delayed after-depolarisations • Circus re-entry • Heart block
Discuss classes of antidysrhythmic drugs with the Vaughan Williams system
- 1a: -Sodium channel blockers, disopyramide
- 1b: -Sodium channel blockers, lignocaine
- 1c: -Sodium channel blockers, flecainide
- 2: -b-adrenoreceptor blockers, sotalol
- 3: -Potassium channel block, amiodarone
- 4: -Calcium channel blockers, verapamil
- Unclassified: adenosine and digoxin
Discuss class 1 antidysrhythmics
Drug binding domains of voltage-gated sodium channels
- Inhibit action potential propagation and they reduce the rate of cardiac depolarisation during phase 0.
- Subdivision to class a, b and c is based on the properties of the drugs in binding to sodium channels in their various states such as open, refractory and resting.
- Depolarisation switches channels from resting to open states- known as activation. Maintained depolarisation causes the channels to move to a refractory state - known as inactivation.
- Cardiac myocytes must repolarise to reset the sodium channels back to resting state.
- These drugs bind to the open and refractory states of the channels and so are viewed as use-dependent i.e. work more effectively if there is high activity and so are more effective against abnormal high frequency activity and not so much against normal beating rates.
Discuss the clinical use of class 1 antidysrhythmic drugs
• Class 1a. Disopyramide (resembles quinidine)
• Ventricular dysrhythmias, prevention of recurrent atrial
fibrillation triggered by vagal over activity.
- Class 1b. Lignocaine (given by IV)
- Treatment and prevention of ventricular tachycardia and fibrillation during and immediately after MI.
- Classs 1c. Flecainide.
- Suppresses ventricular ectopic beats. Prevents paroxysmal atrial fibrillation and recurrent tachycardias associated with abnormal conducting pathways.
Discuss class 2 antidysrhthmics
Beta blockers
• Block b-1 receptors slow the heart and decrease cardiac
output.
• b-1 receptor activation increases the rate of depolarisation of the pacemaker cells so blocking them decreases this.
• b-1 receptor activation enhances calcium entry in phase 2 of the cardiac action potential so blocking them reduces this.
• b-blockers increase the refractory period of the AV node so prevent recurrent attacks of supraventricular tachycardias.
• Basically increased sympathetic drive and influence tend to promote dysrhythmias and so attenuating their influence will slow the heart and decrease their occurrence.
Discuss clinical uses of class 2 drugs - b blockers
• Sotalol, bisoprolol, atenolol. Clinical uses are to reduce mortality following MI and to prevent recurrence of tachycardias provoked by increased sympathetic activity.
Discuss class 3 drugs
Potassium channel blockers
• Amiodarone - prolongs the cardiac action potential by prolonging the refractory period.
Discuss clinical uses of class 3 drugs
- Amiodarone, tachycardia associated with the Wolff- Parkinson-White syndrome. Wolff-Parkinson-White syndrome is a heart condition featuring episodes of an abnormally fast heart rate. Episodes can last for seconds, minutes, hours or (in rare cases) days. They may occur regularly, once or twice a week, or just once in a while.
- Amiodarone is also effective in many other supreventricular and ventricular tachyarrhythmias.
- Sotalol combines class 3 with class 2 actions. It is used in supraventricular dysrhythmias and suppresses ventricular ectopic beats and short runs of ventricular tachycardia.
Discuss class 4 drugs
calcium channel blockers
• Verapamil and diltiazem.
• Blocks cardiac voltage- gated L-type calcium channels.
• Slow conduction through the SA and AV nodes where the conduction of the AP relies on the slow calcium currents.
• They shorten the plateau of the cardiac AP and reduce the force of contraction of the heart.
Discuss clinical uses of class 4 drugs
• Verapamil is the main drug.
• Used to prevent recurrence of supraventricular tachycardias
(SVTs)
• And to reduce the ventricular rate in patients with atrial fibrillation provided they do not have Wolff-Parkinson-White syndrome.
• It is ineffective and dangerous in ventricular dysrhythmias.
• Diltiazem is similar to verapamil but has more effect on smooth muscle calcium channels and has less bradychardia
Discuss adenosine
Unclassified in Vaughan Williams system
- Produced endogenously with effects on breathing, cardiac and smooth muscle, vagal afferent nerves and platelets.
- A1 receptor is responsible for the effect on the AV node.
- These receptors are linked to the same cardiac potassium channels that are activated by ACh. and so it hyperpolarises cardiac conducting tissue and slows the heart rate. It decreases pacemaker activity.
- Used to terminate SVTs.
Discuss digoxin
Unclassified in the Vaughan Williams system
- Cardiac glycosides are a family of compounds that are derived from the foxglove plant (Digitalis purpurea).
- Increase vagal efferent activity to the heart (by unknown mechansim)
- This parasympathomimetic action of digoxin reduces sinoatrial firing rate (decreases heart rate) and reduces conduction velocity of electrical impulses through the atrioventricular node
- Toxic concentrations disturb sinus rhythm. Inhibition of Na+/K+ pump cause depolarisation – ectopic beats
Learning outcomes
- Understand the Vaughan Williams classification of anti-dysrhythmic drugs
- Recognise that some drugs are unclassified on this scheme
- Know the mechanism of action, and uses of the Class I group of drugs
- Recognise the term ““use-dependent”” block
- Understand the mechanism of action, and uses of the Class II group of drugs
- Know the mechanism of action, and uses of the Class III group of drugs
- Understand the mechanism of action, and uses of the Class IV group of drugs
- Know the mechanisms of action, and uses of the unclassified drugs
