Antiarrhythmic Drugs

Question 1

Describe the ventricular action potential

Answer 1

Phase 0 - rapid depolarisation when Na+ enters

Phase 1 - partial depolarisation where Na+ channels become inactivated

Phase 2 - plateau caused by inward Ca2+ currents opposing the outwards K+ movement

Phase 3 - repolarisation due to closing of the L-type and unopposed K+ current

Phase 4 - resting membrane potential determined by K+ permeability

Question 2

Describe the pacemaker potential

Answer 2

No resting membrane potential. The funny current is activated by HCN channels moving Na+ into the cell and when this reaches -50mv it reaches the threshold to generate an action potential. HCN channels inactivate and the upstroke is caused by opening of L-type Ca2+ channels. The downstroke is caused by opening of K+ channels.

Question 3

What is the difference between atrial fibrillation and supra ventricular tachycardia?

Answer 3

Atrial fibrillation is irregularly irregular whereas supra ventricular tachycardia is regular but tachycardic

Question 4

What are delayed after-depolarisations?

Answer 4

Mainly caused by an increase in Ca2+ which reverses NCX allowing Na+ to enter and depolarise the cell early.

Early after-depolarisation occurs before the action potential has completed and can be potentates by hypokalaemia or drugs that increase the QT interval (class III antiarrhythmics)

Question 5

What are re-entry loops?

Answer 5

An impulse re-excites regions after the refractory period has subsided causing a continuous circulation of action potentials that would usually cancel each other out. As a result of structural abnormality or MI

Question 6

What physiological action can cause ectopic pacemaker activity and what does this cause?

Answer 6

Activation of the sympathetic system and can cause tachycardias

Question 7

What causes heart block?

Answer 7

Fibrosis/ischaemic damage to the conducting system

Question 8

How do class I drugs work?

Answer 8

Na+ channel blockers - bind to open Na+ channels and keep them inactivated but dissociates in time for the next action potential so prevents early APs

Question 9

Name a class IA drug

Answer 9

Quinidine, procainamide

Question 10

Name a class IB drug

Answer 10

Lidocaine, phenytoin

Question 11

Name a class IC drug

Answer 11

Flecainide, propafenone

Question 12

What are the ADRs for flecainide?

Answer 12

Pro arrhythmic

CNS - dizziness, drowsiness

GI - nausea, vomiting

Question 13

Describe the pharmacokinetics for flecainide

Answer 13

Oral, CYP2D6, renal excretion

Question 14

How do beta blockers achieve a chronotrophic effect?

Answer 14

They decrease the slope of the pacemaker potential

Question 15

Name the major class III antiarrhythmic

Answer 15

Amiodarone - binds to K+ channels and prolongs the refractory period

Question 16

What are the ADRs of amiodarone?

Answer 16

Hepatic injury, pulmonary fibrosis, thyroid disease, increased LDLs

Question 17

Name a Ca2+ channel blocker

Answer 17

Verapamil, diltiazem - decrease the inwards current of Ca2+ causing a decrease in the slope of the action potential and also reduces the force of contraction

Question 18

How would you treat a supra ventricular tachycardia?

Answer 18

Vagal manoeuvres

IV adenosine/verapamil

Question 19

How does adenosine work?

Answer 19

Binds to A1 receptor which is Gi and reduces cAMP thus increases K+ efflux and leads to hyperpolarisation

Question 20

How would you manage chronic AF?

Answer 20

Anticoagulant

Rate control - beta blocker/verapamil (consider adding digoxin/amiodarone)

Rhythm control - cardioversion (+amiodarone) or pharmacological cardioversion (flecainide)

Question 21

How would you treat acute AF?

Answer 21

Anti coagulation

Emergency cardioversion (+amiodarone) or pharmacological cardioversion (flecainide)

Control rate - verapamil/bisprolol (digoxin/amiodarone second line)

Question 22

How would you treat ventricular tachycardia?

Answer 22

Amiodarone/lidocaine, shock

Question 23

What are the ADRs for verapamil?

Answer 23

Constipation, hypotension, ankle swelling, heart failure

Question 24

How does digoxin work? (Cardiac glycoside)

Answer 24

Has a positive inotrphic effect by blocking Na+/K+ ATPase. This increases intracellular Na+ which reverses the NCX pump so more Ca2+ is stored in the SER and available during contraction

It also has a negative chronotrophic effect by increasing vagaries activity g