Lecture 11 Antiarrhythmic Drugs

Question 1

What is the SAN pacemaker potential?

Answer 1

Upstroke of the slow pacemaker action potential
Triggered at threshold potential (-55mV)
Increase in movement of Ca2+ in cell

Question 2

What are the different phases of SAN pacemaker potential?

Answer 2

Phase 0: Ca2+ influx
Phase 3: Ca2+ channels inactivate, delayed K+ efflux (hyper polarisation)
Phase 4: Pacemaker Na+ influx, Ca2+ channels recover, pump restores ion gradients

Question 3

What is the function of the SAN?

Answer 3

It is the rate of firing that sets the heart rate
It is the initiation of the cardiac cycle

Question 4

What is found in the membrane of the pacemaker cell?

Answer 4

HCN-gated channels (hyperpolarisation-activated cyclic nucleotide-dependent nonspecific channel)

Question 5

What are the properties of phase 4 in the SAN?

Answer 5

It is a prepotential (automaticity)
Activated by hyper polarisation
HCN mediates funny current (K+ efflux and Na+ influx simultaneously)
Na+ influx dominates = slow depolarisation
Reaches threshold
Upstroke inactivates HCN

Question 6

What are the phases of ventricular myocyte action potentials?

Answer 6

0 - Na+ channels open
1 - Na+ channels close, fast K+ channels open
2 - Ca2+ channels open, fast K+ channels close
3 - Ca2+ channels close, slow K+ channels open
4 - Resting potential

Question 7

What types of arrhythmias occur in SAN?

Answer 7

Supraventricular tachycardia

Question 8

What type of arrhythmias occur in cardiac myocytes?

Answer 8

Ventricular tachycardia and ventricular fibrillation

Question 9

How do the sympathetic nerves interact with heart rate?

Answer 9

Activation releases noradrenaline - binds β1 adrenoreceptors on pacemaker and myocyte
Increased opening HCN channels in pacemaker cells - increase Na+ influx (funny current)
Open Ca2+ channels
Increased slope of prepotential (phase 4 SAN)
Heart rate increases

Question 10

How do the parasympathetic nerves interact with heart rate?

Answer 10

Activation release ACh - muscarinic cholinergic receptors
Decreased opening HCN - decreased Na+ influx
Slows opening Ca+ channels
Open additional K+ channels
Hyperpolarises membrane and reduces slope of prepotential (phase 4)
Heart rate decreases

Question 11

What does vagal tone do to the heart?

Answer 11

It allows intrinsic rate of firing of SAN cells
Constant tonic activation of some parasympathetic nerves on SAN (allows slower heart rate for stability)

Question 12

What are early after-depolarisations?

Answer 12

When normal heart rate is low and suppressed by a high heart rate
Occurs when AP is prolonged (Ca2+ channels inactivate)
Reactivate to give EAD
- Ca2+ L channels: end phase 2
- Ca2+ T channels: mid phase 3
Need different drugs to reset

Question 13

What are delayed after-depolarisations?

Answer 13

Increased heart rates
Elevated intracellular Ca2+ concentration
Ca2+ activation of Na/K+ channels (depolarising)
NaCa exchange 3:1 - electrogenic
Seen at toxic doses of cardiac glycosides (e.g. digoxin)

Question 14

What is the Vaughan Williams classification?

Answer 14

It is the different class system of antiarrhythmibc drugs based on mechanism of action
Classes I-IV

Question 15

What are the features of using atropine for arrhythmias?

Answer 15

Antimuscarinic alkaloid
Blocks vagal inhibition of SAN and AVN
IV bolus
Predominantly hepatic metabolism
Short half life
Anticholinergic ADRs - dry mouth, mydriasis (pupils) and postural hypotension

Question 16

What are drugs not classified in the Vaughan Williams classification?

Answer 16

Used in slow heart rhythms or bradycardias - need to increase HR
Atropine - vagus nerve
Isoproterenol - β receptors
Pacing (sympathetic nerve)

Question 17

What are Class I antiarrhythmic drugs?

Answer 17

Na+ channel blockers for abnormal fast heart rhythms - tachycardia
Class IA - moderate Na+ channel block (prolonged repol)
Class IB - mid Na+ channel block (shortened repol)
Class IC - marked Na+ channel block (no change in repol)

Question 18

Name examples of class IA antiarrhythmic drugs

Answer 18

Quinidine, propafenone and disopyramide

Question 19

Name examples of class IB antiarrhythmic drugs

Answer 19

Lignocaine and lidocaine (also used as local anaesthetics)

Question 20

Name examples of class I antiarrhythmic drugs

Answer 20

Flecainide

Question 21

What is the function of lidocaine?

Answer 21

Action - blocks fast Na+ channels, slow phase 0, shorten AP and rapid depolarising of tissue
Used in ventricular arrhythmias
Short half-life (used as bolus IV)
Not absorbed via oral route
Hepatic clearance decreased in elderly, HF and liver disease
ADR: Hypotension, heart block and neurotoxicity and fits

Question 22

What are class II antiarrhythmic drugs?

Answer 22

Treat abnormal fast heart rhythms - tachycardia
Beta blockers - dampen sympathetic nerve
Flatted phase 4 and delay AVN

Question 23

Name examples of class II antiarrhythmic drugs

Answer 23

Non-cardioselective - propranolol
Cardioselective - atenolol
Others - Bretyllium

Question 24

What type of rhythms are beta blockers useful in treating?

Answer 24

Supravntricular tachycardias and atrial fibrillation

Question 25

What is the pharmacokinetics of beta blockers?

Answer 25

Oral and IV First pass hepatic metabolism Renal excretion

Question 26

What are the other actions of beta blockers?

Answer 26

Beta adrenoreceptor antagonist Reduce intrinsic rate I SAN and AVN Reduce heart rate, blood pressure and cardiac work Reduce renin secretion

Question 27

What are the adverse effects of beta blockers?

Answer 27

β1: bradycardias and HF β2: exacerbation of asthma, cool peripheries, muscle aches, worse intermittent claudication (pain in legs)

Question 28

What are the class III antiarrhythmic drugs?

Answer 28

K+ channel blockers - dampen all electrical activity

Question 29

Name an example of a class III antiarrhythmic drug

Answer 29

Amidarone

Question 30

What are the features of amiderone?

Answer 30

Action: prolong action potential duration and refractory period, lengthen QT interval on ECG Indications: Ventricular and supra ventricular tachycardia, 1st line for ventricular fibrillation Pharmacology: long half-life, hepatic metabolism

Question 31

What are the adverse effects of amiderone?

Answer 31

Thyroid disturbances Pulmonary fibrosis Pro-arrhythmia and torsade de pointes (ventricular tachycardia) Peripheral neuropathy Hepatitis Blue-grey skin discoloration

Question 32

What are the class IV antiarrhythmic drugs?

Answer 32

Ca2+ channel blockers (SAN)

Question 33

Name the different class IV antiarrhythmic drugs

Answer 33

Dihydropyridines - nifedipine and amlodipine (vascular) Benzothiazepines - diltiazem (vascular and cardiac) Phenylalkylamine - verapamil (cardiac)

Question 34

What are the features of verapamil?

Answer 34

Actions: Ca2+ channel blocker, slows phase 1/2, reduce rate and conduction velocity in SAN and AVN Indications: supraventricular arrhythmias Pharmacology: blood vessels, oral and IV, 1st pass hepatic metabolism ADRs: HF, hypotension, constipation Vasodilation, oedema and flushing

Question 35

How is adenosine used to treat Wolff-Parkinsone-White syndrome?

Answer 35

Causes further hyper polarisation which allows the heart to restart as the currents are wrong in the myocytes

Question 36

What is adenosine used to treat?

Answer 36

AV node re-entry supraventricular tachycardia

Question 37

What is Wolff-Parkinson-White syndrome also known as?

Answer 37

AV node re-entry supraventricular tachycardia cardia

Question 38

What is used to treat an asystole cardiac arrest?

Answer 38

Adrenaline/epinephrine

Question 39

What is used to treat a ventricular fibrillation cardiac arrest?

Answer 39

Amiodarone and lignocaine (NEVER ADRENALINE)