Antiarrhythmic Drugs

Question 1

Defects in what 2 processes can cause arrhythmias?

Answer 1

Impulse formation and impulse conduction.

Question 2

What are the 2 possible defects in impulse formation?

Answer 2

Altered automaticity and triggered activity.

Question 3

Give an example of physiological altered automaticity?

Answer 3

Modulation of the SA node activity by the ANS e.g. sinus tachycardia, sinus arrhythmia.

Question 4

When does altered automaticity become pathological?

Answer 4

When latent pacemaker subverts the SA node’s function as the normal pacemaker of the heart (overdrive suppression is lost).

Question 5

When may a latent pacemaker subvert the SA node’s function?

Answer 5

1. If the SA node firing frequency is pathologically low (or when conduction from SA node is impaired).
2. If a latent pacemaker fires at a rate faster than the SA node rate.

Question 6

What is the beat called when the SA node firing frequency is pathologically low?

Answer 6

An escape beat (series is called escape rhythm).

Question 7

What is the beat called when the latent pacemaker fires faster than the AV node?

Answer 7

An ectopic beat (series is called an ectopic rhythm).

Question 8

What are the causes of an ectopic rhythm?

Answer 8

Ischaemia, hypokalaemia, increased sympathetic activity, fibre stretch.

Question 9

What is triggered activity?

Answer 9

Afterdepolarisations triggered by a normal action potential.

Question 10

What are the 2 types of afterdepolarisations?

Answer 10

Early afterdepolarisation (EAD) - often Purkinje fibres. Delayed afterdepolarisation (DAD).

Question 11

What phases of the action potential of a cardiac myocyte does EAD occur and what channels mediate the afterdepolarisation?

Answer 11

Phase 2 (plateau) - calcium channels. 
Phase 3 - sodium channels.

Question 12

What are the causes of EAD?

Answer 12

Prolongation of the AP and drugs e.g. sotalol prolonging the QT interval.

Question 13

When does DAD occur?

Answer 13

Occurs after complete depolarisation.

Question 14

What causes DAD?

Answer 14

Ca2+ overload provoked by catecholamines, digoxin and heart failure.

Question 15

What current causes DAD?

Answer 15

Transient inward current involving Na+ influx.

Question 16

What are the 3 defects in impulse conduction?

Answer 16

Re-entry, conduction block and accessory tracts.

Question 17

What is it called when a self sustaining electrical circuit stimulates an area of myocardium repeatedly/rapidly?

Answer 17

Re-entry.

Question 18

In re-entry, what are the 2 requirements of the re-entrant circuit?

Answer 18

1. Unidirectional block (anterograde production prohibited, retrograde conduction allowed).
2. Slowed retrograde conduction velocity.

Question 19

What are the 3 types of conduction block (heart block)?

Answer 19

First degree AV block, second degree AV block (Mobitz type I and II), third degree AV block.

Question 20

Describe first degree AV block.

Answer 20

Slowed conduction (tissue conducts all impulses but more slowly than usual). Long PR interval.

Question 21

Describe second degree AV block.

Answer 21

Tissue conducts some impulses but not others.

Question 22

What is the difference between Mobitz type I and II block?

Answer 22

I - PR interval gradually increases from cycle to cycle until AV node fails completely and a ventricular beat is missed.
II - PR interval constant but every nth beat ventricular depolarisation is missing.

Question 23

Describe third degree AV block.

Answer 23

No impulses are conducted through the AV node.

Question 24

What is the ventricular pacemaker in third degree heart block and what happens to the heart rate and cardiac output?

Answer 24

Purkinje fibres (fire relatively slow and unreliably). Causes bradycardia and low CO.

Question 25

What is a common accessory tract pathway?

Answer 25

The bundle of Kent.

Question 26

What can ventricles receiving impulses from both the normal and accessory pathways cause?

Answer 26

Re-entrant loop predisposing to tachyarrhythmias.

Question 27

What is the classification where anti-arrhythmic drugs are classified pharmacologically?

Answer 27

Vaughn Williams classification.

Question 28

Give an example of an antiarrhythmic drug that blocks more than one channel type.

Answer 28

Amiodarone.

Question 29

Give 2 examples of antiarrhythmic drugs that do not fit into the Vaughn Williams classification.

Answer 29

Adenosine, digoxin.

Question 30

Describe the association and dissociation times of class Ia, b and c antiarrhythmics.

Answer 30

Ia - moderate rate. Ib - rapid rate. Ic - slow rate.

Question 31

What channel do class I block and what part of the cardiac myocyte action potential does it lengthen?

Answer 31

Voltage-activated sodium channel. Phase 0.

Question 32

What is the state of the sodium channel in the refractory period?

Answer 32

Inactivated.

Question 33

What does the relative proportions of time that sodium channels spend in each state depend on?

Answer 33

Firing frequency.

Question 34

During tachyarrhythmias, what states are the sodium channels in the most?

Answer 34

Open and inactivated.

Question 35

What states of sodium channels do class I drugs bind to preferentially?

Answer 35

The open and inactivated states.

Question 36

How does the class I drugs binding to the open and inactivated states preferentially improve the drugs' function?

Answer 36

They target the areas of the myocardium in which firing frequency is highest in a use-dependent manner, without preventing the heart from beating at normal frequencies.

Question 37

Why does steady state block increase when heart rate increases (especially for agents with slow dissociation rates)?

Answer 37

They dissociate during diastole so if heart rate increases there is less time for unblocking and more time for blocking.

Question 38

What features of ischaemic myocardium allows a greater binding of class I drugs to the sodium channels?

Answer 38

Myocytes are partially depolarised and AP is longer so inactivated state of channel is available to blockers for more time and rate of channel recovery from block is decreased.

Question 39

What does the higher affinity of sodium channel blockers for the open and inactivated states of the channel allow them to do?

Answer 39

Act preferentially on ischaemic tissue and block an arrhythmogenic focus at its source.

Question 40

What classes of antiarrhythmic drugs act on the atria?

Answer 40

Class IC and III.

Question 41

What classes of antiarrhythmic drugs act on the ventricles?

Answer 41

Classes IA, IB and II.

Question 42

What classes of antiarrhythmic drugs act on the AV node?

Answer 42

Adenosine, digoxin, classes II and IV.

Question 43

What classes of antiarrhythmic drugs act on the atria, ventricles and AV accessory pathways?

Answer 43

Amiodarone, sotalol, classes IA and IC.

Question 44

What are the drugs used in supraventricular arrhythmias?

Answer 44

Adenosine (IV bolus), digoxin (IV infusion/oral), verapamil (oral).

Question 45

What does adenosine bind to and what channel does this open?

Answer 45

A1-adenosine receptors coupled to Gi/o. Opens ACh-sensitive K+ channels (GIRK).

Question 46

What is the effect on the AV node of adenosine opening GIRK channels?

Answer 46

Hyperpolarises it briefly, suppressing impulse conduction.

Question 47

What is adenosine used to treat?

Answer 47

Paroxysmal supraventricular tachycardia (atrial firing rate of 140-250 bpm) caused by re-entry involving the AV node, SA node or atrial tissue.

Question 48

What is digoxin's effect on the parasympathetic nervous system?

Answer 48

It stimulates vagal activity.

Question 49

What effect does digoxin have on the AV node and bundle of His?

Answer 49

Slows conduction and prolongs refractory period.

Question 50

What is digoxin used to treat?

Answer 50

Atrial fibrillation.

Question 51

What effect does verapamil have on the AV node and bundle of His?

Answer 51

Slows conduction and prolongs refractory period in AV node and bundle of His.

Question 52

What is verapamil used to treat?

Answer 52

Atrial flutter and atrial fibrillation.

Question 53

What may verapamil cause in higher dose?

Answer 53

Heart block.

Question 54

What should verapamil be used with caution with?

Answer 54

Other drugs that have a negative inotropic effect.

Question 55

What was verapamil replaced by for acute treatment, and what is it still used for?

Answer 55

Adenosine, still used for prophylaxis.

Question 56

What drug is used in ventricular arrhythmias?

Answer 56

Lignocaine (IV, type Ib agent).

Question 57

When is lignocaine mainly used?

Answer 57

In the treatment of ventricular arrhythmias following an MI.

Question 58

What are the drugs used in atrial and ventricular arrhythmias?

Answer 58

Disopyramide and procainamide (type Ia), flecainide (type Ic), propanolol and atenolol (type II), amiodarone and sotolol (type III agents).

Question 59

What state of sodium channel does lignocaine mainly block?

Answer 59

Inactivated channels.

Question 60

Why are disopyramide and procainamide use dependent?

Answer 60

They block open sodium channels.

Question 61

What is oral disopyramide used to prevent?

Answer 61

Recurrent ventricular arrhythmias.

Question 62

What is procainamide (IV) used to treat?

Answer 62

Ventricular arrhythmias following MI.

Question 63

What is flecainide used for?

Answer 63

Prophylaxis of paroxysmal AF.

Question 64

What is the ionotropic action of flecainide and what may it trigger?

Answer 64

Has negative ionotropic action and may trigger serious ventricular arrhythmias.

Question 65

How do propanolol and atenolol prevent SVT and VT?

Answer 65

Control SVT by suppressing impulse conduction through the AV node and suppress excessive sympathetic drive that may trigger VT.

Question 66

What effect does amiodarone and sotolol (type III agents) have on re-entry?

Answer 66

Suppress it.

Question 67

Why is amiodarone effective against SVT and VT?

Answer 67

Because it also has class Ia, II and IV actions and also blocks B-adrenoceptors.

Question 68

What diseases does amiodarone reduce mortality after?

Answer 68

MI and congestive heart failure.

Question 69

What adverse effects come with long term use of amiodarone?

Answer 69

Pulmonary fibrosis, thyroid disorders, photosensitivity reactions, peripheral neuropathy.