Lecture 8 - Antiarrhythmics

Question 1

What is the process of generating an action potential in a cardiac myocyte?

Answer 1

AP arrives from neighbouring cells
VG Na+ channels open
Na+ influx (rapid upstroke)
Slight repolarisation as K+ efflux occcurs
Plateau happens as Ca2+ start to be influxed and K+ continues to be effluxed
VG Ca2+ channels close and VG K+ channels open K+ continues to be effluxed so rapid repolarisation occurs
VG K+ channels close
RMP is returned to and maintained by Na/K+ ATPase

Question 2

Go to slide 4:

Describe what’s happening in Step 0 of the Cardiac myocyte AP:

Answer 2

AP arrives from neighbouring cells
VG Na+ channels open
Na+ influx (rapid upstroke/depolarisation)

Question 3

Go to slide 4:

Describe what’s happening in Step 1 of the Cardiac myocyte AP:

Answer 3

Slight repolarisation as K+ efflux occcurs

Question 4

Go to slide 4:

Describe what’s happening in Step 2 of the Cardiac myocyte AP:

Answer 4

Plateau happens as Ca2+ start to be influxed and K+ continues to be effluxed

Question 5

Go to slide 4:

Describe what’s happening in Step 3 of the Cardiac myocyte AP:

Answer 5

VG Ca2+ channels close and VG K+ channels open K+ continues to be effluxed so rapid repolarisation occurs

Question 6

Go to slide 4:

Describe what’s happening in Step 4 of the Cardiac myocyte AP:

Answer 6

Voltage gated K+ channels close
RMP is returned to and maintained by Na/K+ ATPase

Question 7

What principle generates the pacemaker potential at the SAN?

Answer 7

Funny current

Where HCN channels are always open leading to gradual movemtn of Na+ into the SAN cells

Question 8

What are the stages to generating an action potential in the SAN (Pacemaker potential)?

Answer 8

HCN channels are open so Na+ gradually moves into SAN cells producing the Funny Current
Once threshold met, rapid depolarisation/upstrokek occured due to Ca2+ influx through L-Type voltage gated calcium channels
At peak, Voltagee gated Ca2+ channels close and Voltage gated K+ channels open allowing K+ efflux so REPOLARISATION occurs

Question 9

What is the 4 main classes of Anti-arrhythmetic drugs in the Vaughan Williams classification?

Answer 9

Class I (Voltage gated Na+ channel Blockers)
Class II (Beta blockers)
Class III (Voltage gated K+ channel Blockers)
Class IV (Calcium Channel Blocker)

Question 10

What are the 3 classes of Class I anti-arrhythmetic drugs?

Answer 10

Class 1A
Class 1B
Class 1C

Question 11

What is the best example of a Class 1B anti-arrhytmetic?

What channels does it block?

Answer 11

Lidocaine

Voltage gated Sodium channels

Question 12

What is the best example of a Class 1C anti-arrhythmetic drug?

What channel does it block?

Answer 12

Flecainide

Voltage gated sodium channels

Question 13

What is the general principle for how Class I anti-arrhythmetic drugs work?

Answer 13

Block the VG sodium channels slowing the intital upstroke/making it take longer for the upstroke/rapid depolarisation to occur in the cardiac myocytes

Question 14

How do Class IB anti-arrythmetics work?

What is an example of a Class IB anti-arrhythmetic?

Answer 14

Target cardiac myocytes ONLY IN VENTRICLES

Causes a blockade of VG Na+ channels preventing additional impulses occurring

Lidocaine

Question 15

What type of tissue do Class IB preferentially target?

Give an example of a Class IB anti-arrhthymetic:

So what condition is it good for?

Answer 15

Damaged heart tissue

Lidocaine

Myocardial Infarction

Question 16

What is the relative speed by which Class IB anti-arrhthymetics dissociate from the voltage gated sodium channels?

Answer 16

Rapidly dissociate/unblock

Question 17

How does the action of Class IC anti-arrhythmetics differ to Class IB?

Give an example of a Class IC anti-arrhythmetic:

Answer 17

The rate of Na+ ion influx is slowed much more strongly than class IB
So depolarisation occurs later than with Class IB (Lidocaine)

Example = Flecainide

Question 18

What interval do the Class IC anti-arrhythmic drugs affect but this interval is impacted much less than Class IB since the Na+ ion influx happens sooner?

Answer 18

QRS interval prolonged with Class IC

Question 19

What is not affected on an ECG with Class IB anti-arrhythmics but IS with Class IC?

Why is this the case?

Answer 19

QRS interval

The Class ICs delay the upstroke of the QRS way more than Class IBs (class IBs dont prolong it enough)

Question 20

What part of the heart do Class II (beta blockers) target/bind to?

Answer 20

SAN

Question 21

How do Class II anti-arrythmics affect the heart?
(Beta blockers)

Answer 21

Decrease the gradient of the funny current (since blocking the B-adrenoceptors reduces sympathetic tone and so inversely increases parasympathetic tone) = slower heart rate

Decreased uptake of of Calcium (leads to weaker contractions)

Question 22

What is an example of a Class II anti-arryhthmic?

Answer 22

Beta blocker

Bisoprolol
Atenolol

Question 23

What type of anti-arrhythmic is a Class III anti-arrhythmic?

Answer 23

K+ Channel blocker

Question 24

What is the best example of a Class III anti-arrhythmic? (K+ channel blocker)

Answer 24

Amiodarone

Question 25

What part of the heart do Class III K+channel blockers affect?

Answer 25

Cardiac myocytes

Question 26

What is the effect of Class III anti-arrhythmics (K+ channel blockers) on the action potential cycle?

Answer 26

Prolongs repolarisation (by preventing the K+ efflux)

Question 27

What interval on the ECG do Class III K+ channel blockers affect? What is an example of a Class III anti-arrhythmic?

Answer 27

Prolongs the QT interval Since it prolongs repolarisation Amiodarone

Question 28

What are 2 examples of Class IV anti-arrhythmics? What type of drug are these?

Answer 28

Calcium channel blockers (Non dihydropyridines) Verapamil = phenylalkylamine Diltiazem = benzothizapine

Question 29

What part of the heart do Class IV (Ca2+ channel blockers) target?

Answer 29

SAN + Cardiac myocyets So affects pacemaker potential

Question 30

How do Class IV anti-arrhythmics work? What are 2 examples?

Answer 30

SAN: Block L-type voltage gated Ca2+ channels This slows the speed at which the depolarisation/upstroke happens once the threshold potential has been reached Cardiac myocytes: Blocks the L-type voltage gated Ca2+ channels which prolongs the plateau phase due to the Ca2+ channel blockade Verapamil Diltiazem

Question 31

How do Class IV calcium channel blockers prolong the plateau phase in cardiac myoctes?

Answer 31

Reduced rate of influx of Ca2+ leads to a decreased rate of efflux of K+ which leads to a prolonged plateau phase

Question 32

Which class of drug prolongs the QT interval? What is an example of this drug? How does it do so?

Answer 32

Class III (K+ channel blocker) Amiodarone Blocks the K+ channels slowing down/prolonging repolarisation Repolarisation is the QT interval

Question 33

What drug class causes QRS prolongation? How does it do this? What is an example?

Answer 33

Class IC Delays QRS upstroke (Na+ influx) from happening lenghthening the QRS interval

Question 34

What is represented by the PR interval?

Answer 34

The time taken for the AV node to conduct the electrical impulse from the atria to the ventricles

Question 35

What classes of anti-arrhythmics prolong the PR interval and so work at the AV node?

Answer 35

Beta blockers (Class II) Calcium Channel blockers (Class IV)

Question 36

What is the negative effect of Amiodarone (Class III) prolonging the QT interval?

Answer 36

Can induce arrhythmia By prolonging the QT interval/repolarisation time too much you increase the risk of getting early after depolarisations and so arrhythmias

Question 37

What are 3 examples of anti-arrhythmic medications that dont fit in the 4 classes?

Answer 37

Digoxin Ivabradine Adenosine These are considered Class V drugs (miscellaneous)

Question 38

What class of drug is Digoxin?

Answer 38

Cardiac glycoside

Question 39

How does digoxin work as an anti-arrhythmic drug?

Answer 39

AV node blockade (slows AVN transmission) Stops the Na+/K+ ATPase leading to activity of the Na+/Ca2+exchanger to cease so levels of Ca2+ in the cells increase increasing the strength of contraction (+ve inotropy)

Question 40

What is digoxin typically used for?

Answer 40

Heart failure Arrhythmias

Question 41

How does Ivabradine work as an anti-arrhythmic?

Answer 41

Slows heart rate Inhibts the pacemaker current at the SAN so slows the rate at which the threshold potential is reached slowing heart rate

Question 42

When is Ivabradine typically used?

Answer 42

Angina Coronary disease Arrhythmias

Question 43

How does Adenosinei work to treat arrhythmias?

Answer 43

Stimulates A1 adenosine receptors at the AV node blocking the AV node preventing/reducing impulse travelling from atria to ventricles This reduces rate of contraction of ventricles

Question 44

What is adenosine typically used to treat?

Answer 44

Supraventricular tachycardia when the heart is beating extremely fast to the point you cant see what the atria are doing on an ECG

Question 45

How long does adenosine last for as an anti-arrhythmic?

Answer 45

Couple seconds (very short lasting)

Question 46

What is a contraindication of using class I anti-arrhythmics like Flecainide?

Answer 46

Structural heart diseases (changes that occur following MI) since it increases risk of arrhythmias

Question 47

What is a contraindication of using Class II anti-arrhythmics?

Answer 47

Consider alternate treatments like CCB (verapamil or diltiazem) if ASTHMATIC Don’t prescribe with Diltiazem or verapamil

Question 48

Why shouldn’t you prescribe Class II anti-arrhythmias with diltiazem or verapamil?

Answer 48

Beta blockers also work on the SAN like the calcium channel blockers (non-dihydropyridines) verapamil and diltiazem

Question 49

What is a contraindication for using class IV anti-arrhythmics (CCB)?

Answer 49

HFrEF

Question 50

What are the negative side effects/adverse effects of Class III anti-arrhythmics like Amiodarone?

Answer 50

Hepatotoxic Lung fibrosis Optic neuritis Thyroid toxicity Peripheral neuropathy

Question 51

What is a very effective drug for putting the heart back into sinus rhythm?

Answer 51

Amiodarone

Question 52

What are the 2 general ways we get arrhythmias?

Answer 52

Generate abnormal impulses (ventricular ectopics) Or Conduct impulses abnormally (heart block, re-entry loops or accessory pathways)

Question 53

What is atrial fibrillation?

Answer 53

Irregularly irregular contractions/electrical activity of the atria

Question 54

What are the 2 methods by which you can try and stop an atrial fibrillation?

Answer 54

Rate control Rhythm control

Question 55

What is meant by rate control for trying to treat Atrial fibrillation?

Answer 55

Slow the rate of transmission from atria to the ventricles

Question 56

What is meant by rhythm control for trying to treat Atrial fibrillation?

Answer 56

Stop the abnormal rhythm

Question 57

If we are trying to reduce rate of excitation in atrial fibrillation, what heart structure do we need to target?

Answer 57

AV node (needs blocking)

Question 58

What are some drugs that can block the AV node to control rate for Atrial fibrillation?

Answer 58

Adenosine (TOO SHORT LASTING, Afib will come back) CCB (depending on HF status) B-Blocker (depends on asthma status) Digoxin (depends of exercise tolerance, lots of exercise people don’t tolerate well)

Question 59

What drugs can be used to terminate the rhythm of Atrial Fibrillation?

Answer 59

Flecainide Amiodarone Sotalol Cardio version

Question 60

What type of control, rate or rhythm is best for treating an atrial fibrillation?

Answer 60

Young = rhythm control Most = rate control

Question 61

What class of anti-arrhythmic is sotalol?

Answer 61

Class III not Class II