Antiarrhytmics

Question 1

Class 1 – voltage-gated Na channel blockers
(divided into 1a, 1b and 1c)

Answer 1

Blocking the none-pacemaker tissues (the atrial-ventricular tissues), that are generating abnormal tissues.

Goal is to reduce max rate of depolarization during phase 0.

Type a, b and c block the Na channels in different degrees.

Question 2

Class 1a (quinidine, procainamide, disopyramide)

Answer 2

Middle/moderate blockade.
(a decreased slope, but not as decreased as c).
The action potential duration is increased – the effective refractory period is increased. (it also has a little bit of potassium blockade, and therefore it takes longer time for the cell to repolarize).

Question 3

Class 1b (lidocaine)

Answer 3

Least amount of blockade.
(a small decreased slope).
The action potential duration is slower and
refractory period is decreased. This is because the sodium channels are blocked in the active and inactive state.

Side-effects: actions on CNS (drowsiness, disorientation, convulsions (rapid, involuntary muscle contractions)).

Question 4

Class 1c (flecainice, encainide)

Answer 4

The strongest blocker. (A decreased slope in phase 0).
The action potential duration is the same.

Question 5

Class 2 – Beta blockers (e.g. metoprolol)

Answer 5

MOA: Increased sympathetic activity (adrenaline) affects the pacemaker potential -> can cause ventricular dysrhythmias after myocardial infarction -> treat with beta blockers to target the sympathetic nervous system.

Effect: Increase the refractory period of the AV node and can therefore prevent recurrent attacks of supraventricular tachycardia.

Side-effects: hypotension, negative inotropy (weaken the heart’s contraction and slows heart rate), bradycardia, bronchospasms, fatigue.

Question 6

Class 3 – potassium channels blockers (amiodarone, sotalol)

Answer 6

MOA: Prolong the cardiac action potential by blocking some of the K channels in repolarization.

Effect: Prolongation of action potential increases the refractory period -> interrupts re-entrant tachycardias and suppresses ectopic activity -> yields antidysrhythmic activity

Side-effects: Prolonged QT interval on the ECG.

Question 7

Class 4 – Ca channels blockers (verapamil)

Answer 7

Verapamil: slows conduction in the SA and AV nodes where action propagation depends on inward Ca current -> causes partial AV block -> terminates supraventricular tachycardia.
Mechanism: shortens the plateau of the action potential -> reduces the force of contraction -> reduces Ca influx -> suppresses the premature ectopic beats.

Side-effects: include negative inotropy so they can’t be used in heart failure patients, and hypotension due to inhibition of smooth muscle calcium channels.

Question 8

Adenosine (unclassified anti-arrhythmic)

Answer 8

Adenosine binds to its receptor, A1 located on the surface of cardiac cells, particularly in the AV node. Activation of A1 receptor lead to the activation of potassium channels, which allow influx of potassium ions out of the cell, leading to hyperpolarization. This reduces the likelihood of depolarization and action potential firing, effectively slowing down the rate of the heart.

Side-effects: chest pain, shortness of breath, dizziness, and nausea.

Question 9

Organic nitrates (anti-anginal drugs)

Answer 9

Relaxation of smooth muscle and veins (are powerful vasodilators) -> reduces cardiac preload and afterload -> reduces cardiac work -> reduces myocardial oxygen requirement.
Diverts blood from normal to ischaemic areas of myhocardium.

Mechanism: metabolized with the release of NO -> activates soluble guanylyl cyclase -> increases cGMP -> activates protein kinase G -> dephosphorylation of myosin light chain chains and sequestration of Ca -> relaxation of smooth muscle.

Side-effects: postural hypotension, headache.

Question 10

Calcium antagonist (anti-anginal drugs)

Answer 10

Mechanism: bind to alfa subunit of L-type Ca channel -> prevent channel opening ->reduces Ca entry. Can cause AV block and have negative inotropic effect (less force of contraction).

Side-effects: flushing, headache, heart block, heart failure, oedema, constipation.

Question 11

Beta-blockers (anti-anginal drugs)

Answer 11

MOA: Decrease the patient’s heart rate and the contractility of the heart. -> decreased cardiac output ->decreased cardiac work -> decreased oxygen consumption -> decrease oxygen demand.

Indication: Treats patients with unstable angina.

Side-effect: bradycardia, hypotension, bronchospasm.