anti arrhythmic drugs

Question 1

What are class III anti-arrhythmic agents ?

Answer 1

They are potassium channel blockers that inhibit potassium outward current or refflux.

Question 2

Class I agents work by blocking ____________

Answer 2

Cardiac voltage-operated sodium channels

Question 3

list four class 2 anti arrhythmic agents?

Answer 3

propranolol (non-selective)

atenolol

metoprolol

bisoprolol (ß1-adrenoceptor (cardio)selective)

Question 4

The major anti-arrhythmic action of class 1 therapeutic contributions are to interrupt ________

Answer 4

re-entry circuits and reduce automaticity

Question 5

Class 1 chief related site of action is phase 0 of non-nodal Myocardial cells, what do they do to stop arrhythmias?

Answer 5

they act on Myocardial cells; and in particular, rapid sodium inward current during (phase 0) depolarisation.

Question 6

with class 1 agents, Sodium entry is inhibited and phase 0 depressed. what is achieved by doing this?

Answer 6

Reduced excitability and slowed impulse conduction (decreased conduction velocity)

Question 7

Class I agents are further subdivided into class _________

Answer 7

IA, IB and IC

Question 8

class IA agents exhibit the additional property of _____________ (which leads to an extended action potential arising from a protracted phase 2/delayed phase 3

Answer 8

Potassium channel blockade

Question 9

List three three class 1 drugs

Answer 9

Flecainide (Class 1C agent)

Lidocaine (Class 1B agent)

Quinidine (Class 1A agent)

Question 10

List the mechanism of Lidocaine

Answer 10

Mild sodium channel blockade

Associates and dissociates rapidly with sodium channel, prefers open and inactivated states for binding, targets ischaemic tissue with little effect on normal myocardium

Question 11

List the mechanism of Flecainide

Answer 11

Marked sodium channel blockade

Associates and dissociates slowly with sodium channel, affects normal + damaged myocardium non-selectively

Question 12

List the mechanism of Quinidine

Answer 12

Moderate sodium channel blockade

Associates and dissociates at intermediate rate with sodium channel

Question 13

Name three class III anti-arrhythmic agents

Answer 13

amiodarone,

dronedarone

vernakalant

Question 14

What are the effects of class III anti-arrhythmic agents ?

Answer 14

Delays phase 3 repolarisation (inhibit potassium loss) and extends phase 2 in non-nodal cells.

Increases action potential duration and refractory period

Reduce possibility of re-entry circuits

Question 15

What are class IV anti-arrhythmic drugs?

Answer 15

calcium entry blockers of the non-dihydropyridine class, which exhibit pronounced activity at voltage-operated, cardiac L-type calcium channels

Question 16

What are examples of class IV anti-arrhythmic drugs?

Answer 16

verapamil, diltiazem

Question 17

What are the effects of class IV anti-arrhythmic drugs?

Answer 17

Reduce nodal excitability and a reduced heart rate (negative chronotropy) + firing rate of SAN + conduction rate of AVN

Increase action potential duration + refractory period in nodal cells

Reduce action potential duration + refractory period in non-nodal cells

Provide ventricular rate control in atrial tachycardia and reduce triggered automaticity

Question 18

what do class II anti arrhythmic agents do

Answer 18

Block catecholamine + cAMP-mediated electrical events in: phase 4 of nodal tissue (slope depressed); phase 2 of non-nodal tissue (extended due to delayed onset of phase 3 + reduced calcium entry)

Increase action potential duration + refractory period

Oppose pro-arrhythmic actions of catecholamines
Prevent sinus tachycardia, abnormal + triggered automaticity

Question 19

list 4 class II anti arrhythmic agents?

Answer 19

propranolol (non-selective)

atenolol

metoprolol

bisoprolol (ß1-adrenoceptor (cardio)selective)

Question 20

________-are very simply beta-adrenoceptor antagonists

Answer 20

class II anti arrhythmic agents

Question 21

list 3 selective or cardio-selective beta1-adrenceptor blockers

Answer 21

atenolol

metoprolol

bisoprolol

Question 22

list the non-selective beta1-adrenceptor blockers.

Answer 22

propranolol

Question 23

explain the mechanism for beta-adrenoceptor antagonists or class II anti arrhythmic agents.

Answer 23

hese agents prevent cardiac signalling by the catecholamine beta1-adrenoceptor agonists noradrenaline and adrenaline. Beta-adenoceptor blockade results in a fall in cAMP levels and cAMP-mediated intracellular events. These include events in nodal tissue like the SAN, to enhance the pacemaker current and raise the slope of phase 4 (causing a rise in heart rate or sinus tachycardia) and an associated shortening of phase 2 in non-nodal tissue (owing to an acceleration of phase 3 repolarisation). These 2 events orchestrated by cAMP are complementary, as the rise in heart rate in response to e.g. adrenaline must be accommodated by a reduced action potential duration – there is basically less time for the action potential between heart beats. At the same time as adrenaline-induced tachycardia, e.g. during a general sympathetic discharge or “fight-or-flight” response, there is also an increase in cardiac force of contraction (or positive inotropy). This increase in force may at first sound at odds with the short (non-nodal) phase 2 (i.e. the window for calcium entry needed for calcium-induced calcium release and ultimately for contraction) caused by adrenaline; but the fact is that cAMP also enhances calcium entry through L-type calcium channels in phase 2. This then provides more calcium-induced calcium release (from the sarcoplasmic reticulum) for contraction, in the face of a shorter phase 2. The major anti-arrhythmic outcomes of beta-adrenoceptor blockade are therefore predictably: depressed nodal phase 4 slope and lowered heart rate; and prolonged non-nodal phase 2 owing to a delayed phase 3, which extends action potential duration and refractory period. Hence, class II agents prevent automaticity related to excessive signalling activity by catecholamines (e.g. during ischaemia, myocardial infarction and heart failure) while also reducing heart rate (negative chronotropy). Cardiac beta-adrenoceptor blockade is also typically associated with negative inotropy.

Question 24

which class II anti arrhythmic agents is cardiac selective

Answer 24

bisoprolol

Question 25

Class 1 chief related site of action is

Answer 25

phase 0 of non-nodal myocadiac cells

Question 26

___________prefers open and inactivated states for binding, targets ischaemic tissue with little effect on normal myocardium

Answer 26

lidocaine

Question 27

_________________Associates and dissociates slowly with sodium channel, affects normal + damaged myocardium non-selectively

Answer 27

Flecainide

Question 28

_____________Associates and dissociates at intermediate rate with sodium channel

Answer 28

quinidine