Antiarrhythmics Flashcards
Anti-arrhythmics are drugs that modify cardiac conduction, they are used to treat arrhythmias and are classified according to the Vaughan-William’s system.
This classification divides these drugs into four classes according to their effects on cardiac action potential. Anti-arrhythmics have complex actions and classes may overlap.
It is important to note, that this classification system has become increasingly inadequate with improved understandings of drug mechanisms and development of new antiarrhythmics.
What are arrhythmias?
Arrhythmias are disorders of rate and rhythm of the heart, which arise due to either abnormal generation or conduction of electrical impulses.
Increased automaticity - arrhythmias
Occurs when tissue other than the SA node develops spontaneous depolarization that supersedes the SA node itself.
The origin may be:
Conduction pathway - i.e. specialised autorhythmic cells.
Contractile tissue - contractile cells may gain autorhythmic function for various reasons, e.g. ischaemia.
Re-entry -
Begins when an electrical impulse reaches a branch in which one pathway is refractory (i.e it is not yet repolarised and as such cannot depolarise). The impulse simply passes down the conducting pathway and may meet the distal part of the refractory tissue once it has repolarised. The impulse may then be transmitted retrogradely through the this tissue.
A circuit is established. These circuits termed re-entry circuits may act as a pacemaker and trigger aberrant rhythms.
Re-entry is thought to be the cause of most clinically relevant arrhythmias.
… is thought to be the cause of most clinically relevant arrhythmias.
Re-entry is thought to be the cause of most clinically relevant arrhythmias.
Triggered activity
Arrhythmias
Damage to the myocardium may lead to oscillations of membrane potentials at the end of the action potential, termed afterdepolarisations.
These afterdepolarisations may occur during (early) or following (delayed) repolarisation.
Digoxin toxicity results in arrhythmias due to this mechanism.
Class IA antiarrhythmics and Sotalol may cause prolonged QT with an increased risk of … ventricular tachycardia (torsades des pointes).
Class IA antiarrhythmics and Sotalol may cause prolonged QT with an increased risk of polymorphic ventricular tachycardia (torsades des pointes).
Class I antiarrhythmics slow depolarisation and with it conduction. These drugs act to reduce sodium entry through inhibition of fast sodium channels. The subtypes have variable effects on cardiac action potential.
- Class IA
Phase 0: Depress
Action potential: increases the duration of the action potential through inhibition of potassium channels.
Examples: Quinidine, Procainamide, Disopyramide.
Rarely used in the UK due to adverse effects.
2. Class IB
Phase 0: Depress
Action potential: decreases the duration of the action potential
Examples: Lidocaine, Phenytoin.
3. Class IC
Phase 0: Markedly depress
Action potential: no effect
Examples: Flecainide.
Adverse effects of class I antiarrhythmics
Nausea & vomiting
Negative inotropic effect
Proarrhythmic effects
CNS toxicity (Class IB and IC in particular)
SLE-like syndrome (Procainamide)
Cinchonism (condition caused by Quinidine overdose)
Class II antiarrhythmics are antagonists of catecholamines at beta-adrenoceptors. They possess both negative inotropic and negative chronotropic properties.
They act on the AV node to reduce conduction and have variable selective action on beta-1 receptors (predominantly found in the heart) and beta-2 receptors (predominantly found in the lungs).
Examples: Propranolol, Bisoprolol.
Name the class
Beta blockers which act to reduce sympathetic activity.
Mechanism of action of beta blocker
Antagonists of catecholamines at beta-adrenoceptors, possessing both negative inotropic and negative chronotropic effects; that is they reduce heart rate and the strength of contractions.
They act on the SA node to reduce the rate of spontaneous depolarisation (and so reducing the heart rate) by decreasing the slope of phase 4. In essence, slowing the spontaneous depolarisation of the pacemaker potential. They also act on the AV node to reduce conduction.
Adverse effects of beta blockers?
Postural hypotension Bradycardia AV nodal block (heart block) Bronchoconstriction (a particular consideration in severe asthma and COPD) Hypoglycaemia Erectile dysfunction Insomnia, sleep disturbance
Class III antiarrhythmics - A mixed category of drugs which prolong action potential, typically by blocking potassium channels.
Examples?
Class III is a mixed category composed of drugs that prolong cardiac action potential, typically via blocking potassium channels.
Examples: Amiodarone, Sotalol.
Which antiarrhythmics prolong the action potential?
A mixed category of drugs which prolong action potential, typically by blocking potassium channels.
Class III is a mixed category composed of drugs that prolong cardiac action potential, typically via blocking potassium channels.
Examples: Amiodarone, Sotalol.
Mechanism of action of class III antiarrhythmics
Block potassium channels, which are responsible for the completion of repolarisation (phase 3) in contractile cells. Blockade leads to an extension of the refractory period, through the prolongation of phase 2.
Amiodarone adverse effects
Nausea Constipation Thyroid dysfunction (see our Hyperthyroidism and Hypothyroidism notes) Peripheral neuropathy Photosensitivity Lung fibrosis Proarrhythmic effects Hepatitis / cirrhosis Potentiates the effects of both digoxin and warfarin.
Non-dihydropyridine CCBs that act to reduce conduction at the AV node.
A number of antiarrhythmics do no fit in the Vaughan-Williams classification. (List 4)
