lecture 24 - classification and mechanisms of anti-arrhythmic drugs

Question 1

what are arrhythmias?

Answer 1

a group of conditions in which the heart beats irregularly, too fast or too slowly and as a result causes abnormal electrical activity

Question 2

what is an abnormality of the cardiac rhythm called?

Answer 2

cardiac arrhythmia

Question 3

where may arrhythmias arise from?

Answer 3

ischaemia, infarction, fibrosis or drugs

Question 4

what are two main types of arrhythmias?

Answer 4

irregular bradycardia - <60 bpm

irregular tachycardia - >100 bpm

Question 5

where can arrhythmias be classified from the site of origin?

Answer 5

atria, junction AV, ventricle

Question 6

what kind of cells are sa and av nodes and what do they use in their action potential upstroke?

Answer 6

Sinoatrial node and atrioventricular node cells are ‘slow conductors’ that use calcium channels mainly in their action potential upstroke (thus blocked by calcium channel blockers)

Question 7

what kind of cells are atrium, bundle of his and ventricle cells?

Answer 7

fast conductors - that use sodium channels mainly in their action potentials upstroke
9thus blocked by sodium channel blockers)

Question 8

what are two main important features of channels?

Answer 8

gating

ion selectivity

Question 9

what is gating channel control mechanism of what are types of gated channels?

Answer 9

one gating control mechanism is membrane potential

three main types of gates are chemically-gated or ligand-gated channels, voltage gated channels and mechanically gated channels.

Question 10

what do ion selectivity channels do?

Answer 10

some channels only allow for sodium ions to cross others only allow potassium ions, others only calcium ions

Question 11

what ions have a high concentration outside the cell in membrane potentials?

Answer 11

sodium and calcium

Question 12

what ion has a high con inside the cell?

Answer 12

potassium

Question 13

what are fundamental features of a cardiac excitation?

Answer 13

excitability, refractory period. and membrane responsiveness

Question 14

what is excitability?

Answer 14

ability to respond to a stimuli by producing and conducting action potentials

Question 15

what is refractory period?

Answer 15

time following excitation during which a second action potential can not be elite and conducted (ARP vs RRP)

Question 16

what is membrane responsiveness?

Answer 16

relationship between mean activation voltage and the maximal rate of rise of the action potential

Question 17

what do effective anti arrhythmic drugs do?

Answer 17

increase the refractory period or slow the upstroke of action potentials or both

Question 18

what do the drugs work to do?

Answer 18

drugs work to control electrical signals by altering action potentials generation or propagation

Question 19

where do class I anti arrhythmic drugs bind do?

Answer 19

class I antiarrhytmic drugs are sodium channel blockers, targeting phase 0 depolarisation

Question 20

where do class II antiarrhythmic drugs target?

Answer 20

class II anti-arrhythmic drugs are beta blockers and they target the SA and AV node conduction and cardiac contractility

Question 21

what are class III anti-arrhythmic drugs and what do they do?

Answer 21

potassium channel blockers. they increase the repolarisation period, phase 3

Question 22

what are class IV anti-arrhythmic drugs and what do they target?

Answer 22

calcium channel blockers

they target the AV node and also affect cardiac contractility

Question 23

what do class IA drugs do?

Answer 23

decrease membrane reposnsiveness (moderate inhibition of Na channels) eg quinidine, prcainamide, disopyramide

Question 24

what do class 1B drugs do?

Answer 24

minimal inhibition of sodium channels

Question 25

what do class IC drug do?

Answer 25

decrease the mean responsiveness. major inhibition of membrane reponsiveness eg flecainide

Question 26

describe the mechanism of action of class II bet ablcokers eg metoprolol on the action potential

Answer 26

block the effects of catecholamines at the beta-adrenergic receptors, thereby reducing calcium ions influx, decreasing SA and AV node conduction (thus HR) and also cardiac contractility

Question 27

describe the mechanism of action of class III drugs and give examples

Answer 27

A ‘dirty drug’, inhibits K channels (delays repolarization), Na channels and Ca channels (slight), blocks beta-receptors non-competitively, and blocks alpha receptors.

Approved for ventricular tachycardia, ventricular fibrillation and paroxysmal supraventricular tachycardia, used in other arrhythmias as well.

Extremely long and variable half life (approximately 50 days), metabolized in liver.

examples are amiodarone, sotalol

Question 28

describe the mechanism f action of class IV drugs calcium channel blockers

Answer 28

Blocks mainly L-type calcium channels

Slows conduction through the AV node, increases refractory period of AV node, and also reduce cardiac contractility

Useful mainly in supraventricular arrhythmias or ventricular arrhythmias caused by coronary spasm

Question 29

how do class V anti-arrhythmic drugs work and give examples

Answer 29

unknown mechanism

examples: digoxin, adenosine, magnesium sulfate

Question 30

what kind of drug is digoxin and describe how it increases force of Myocardial contraction

Answer 30

inotropic drug
Digoxin – a cardiac glycoside extracted from foxglove leaves.

Inhibits the Na+/K+-ATPase, which is responsible for Na+/K+ exchange across the cell membrane
increases [Na+]in
increases [Ca2+]in
increases force of myocardial contraction.

Question 31

what are the direct effects of digoxin on action potential and refractory period?

Answer 31

Direct Effects:
-Increased [Ca2+]in stimulates K+ channels, and shorten action potential and refractory period (atria & ventricles)
-Increased [Ca2+]in may cause depolarization after normal action potential, which may generate another action potential, causing ectopic beat.