Pharmacology of anti-arrhythmic medications

Question 1

What are the two mechanisms of arrhythmias?

Answer 1

defects in impulse formation- SA-node automaticity is interrupted, or altered (missed beats, ectopic beats

defects in impulse conduction- re-entrant rhythm

Question 2

What are the classes of Anti-arrhythmic drugs?

Answer 2

(I, II, III, IV) with I classified into Ia, Ib and Ic

Question 3

Why are the classifications not solid?

Answer 3

many anti-arrhythmic agents are not entirely selective blockers of Na+, K+ or Ca2+ and many block more than one

Question 4

What do class I Anti-arrhythmic drugs do?

Answer 4

block voltage activated sodium channels

Question 5

What do class Ia Anti-arrhythmic drugs do?

Answer 5

bind to and unbind from voltage activated sodium channels at a somewhat slower rate- slow the rate of rise of the action potential and also prolong the duration of action of the action potential- increase the amount of time that the sodium channels spend in the inactivated or refractory state

Question 6

What do class Ib Anti-arrhythmic drugs do?

Answer 6

help to stop one action potential arising too quickly after another action potential.

Question 7

What do class Ic anti-arrhythmic drugs do?

Answer 7

associate and dissociate from the sodium channel with slow kinetics, greatly depresses the rate of rise of the action potential but has little effect on its duration, strongly supress conduction

Question 8

What do class II anti-arrhythmic drugs do?

Answer 8

fundamentally B adrenoreceptor blockers, very useful in stress induced arrhythmias, decrease effect of sympathetic system upon the nodes

Question 9

What do class III anti-arrhythmic drugs do?

Answer 9

act to block voltage activated potassium channels- work on depolarizing phase of the action potential- prolong action potential, increases refractory period and decreases the frequency of action potential

Question 10

What do class IV anti-arrhythmic drugs do?

Answer 10

block Voltage-activated Ca2+ channels - supress upstroke in nodal tissue, reduce the amount of calcium that enters

Question 11

What are the three states of sodium channels?

Answer 11

resting (non-conducting)
open state (conducting)
inactivates state (non-conducting)

Question 12

Which state do class I agents act preferentially upon?

Answer 12

have little effect upon the resting channels and work preferentially on open and inactivated channels

Question 13

What is the mechanism of action of class I agents?

Answer 13

some class I agents bind selectively to the open state and make in non-conducting

others bind to the inactivated state and slow the transition to the resting state (stabilize the channel)

they will target the sodium channels which are being opened most frequently- not much effect on sinus but huge effect on tachycardia

Question 14

Which area of the heart do class one agents have little affect upon?

Answer 14

little effect on myocardium which is beating at a normal frequency because the time available for them to block open state or stabilize inactivated state is limited, as opposed to a ventricular tachycardia where class I agents will act preferentially on these channels

Question 15

What does class I agent use depend on?

Answer 15

effect of drug will depend on frequency at which its molecular target is being used

Question 16

Name a class Ia agent?

Answer 16

Disopyramide

Question 17

Name a class Ib agent?

Answer 17

Lignocaine

Question 18

Name a class Ic agent?

Answer 18

Flecainide

Question 19

Name a class II agent?

Answer 19

Metoprolol

Question 20

Name a class III agent?

Answer 20

Amiodarone

Question 21

Name a class IV agent?

Answer 21

Verapamil