Molecular Mechanisms of Arrhythmias & Antiarrhythmic Drugs

Question 1

Almost all arrhythmias are:

Answer 1

acquired: (MI), ischemia,
acidosis, alkalosis, electrolyte abnormalities.

Drug toxicity is a common cause of arrhythmia

Question 2

cardiac Na+ channels
cardiac Ca2+ channels
cardiac K+ channels
β-adrenergic receptors (βAR)

Answer 2

primary targets of antiarrhythmic drugs

Question 3

To date, only β-blockers have been demonstrated to reduce the incidence of_______

Answer 3

sudden cardiac death

Question 4

Usually, catheter ablation of ectopic foci and implantable __________ are very often used in place of drugs

Answer 4

cardioverterdebrillator devices (ICDs)

Question 5

primary targets of antiarrhythmic drugs

Answer 5

cardiac Na+ channels
cardiac Ca2+ channels
cardiac K+ channels
β-adrenergic receptors (βAR)

Question 6

If, ICa-L, and IKs are indirect targets of antiarrhythmic drug action via

Answer 6

Via the β-adrenergic receptor pathway:

Question 7

Prolonged QT is caused by

Answer 7

taking too long to repolarize, increased AP duration

Question 8

Mutations in some _____ can cause a prolonged QT interval

Answer 8

sodium and potassium channels.

Question 9

ventricular fibrillation results in a survival rate of only 40% by 5 years of
age
> 30 mutations in the cardiac Na+ channel reduce peak inward Na+ current in ventricular myocytes

Answer 9

Brugada syndrome

Question 10

Two major sources of inappropriate impulse initiation:

Answer 10

a. ) ectopic foci

b. ) triggered afterdepolarizations: triggered by action potentials

Question 11

an excitable group of cells that causes a premature heart beat outside the normally functioning SA node of the human heart

Answer 11

ectopic focus

Question 12

abnormal depolarizations of cardiac myocytes that interrupt phase 2/phase 3 of the cardiac action potential in the electrical conduction system of the heart.

Answer 12

triggered afterdepolarizations: triggered by action potentials

Question 13

Prolonged phase 2 causes excess:

Answer 13

Ca entry

Question 14

Disturbed impulse conduction

Answer 14

-Reentry

Question 15

Reentry factors that can be combated

Answer 15

• unidirectional conduction block in fx circuit

- conduction time around the circuit > refractory

Question 16

Class I: blockers of voltage-gated cardiac Na+ channels

Class II: β-adrenergic receptor blockers (“β blockers”)

Class III: drugs that prolong fast response phase 2 by delaying repolarization

Class IV: blockers of voltage-gated cardiac Ca2+ channels

Answer 16

Vaughan Williams classification of antiarrhythmic drugs

Question 17

blockers of voltage-gated cardiac Na+ channels

Answer 17

Vaughan Williams classification of antiarrhythmic drugs

Class I

Question 18

β-adrenergic receptor blockers (“β blockers”)

Answer 18

Vaughan Williams classification of antiarrhythmic drugs

Class II

Question 19

drugs that prolong fast response phase 2 by delaying repolarization

Answer 19

Vaughan Williams classification of antiarrhythmic drugs

Class III

Question 20

blockers of voltage-gated cardiac Ca2+ channels

Answer 20

Vaughan Williams classification of antiarrhythmic drugs

Class IV

Question 21

adenosine is class?

Answer 21

trick question, unclassified

Question 22

Class Ia drugs: Na+ channel blockers

Answer 22

Class IA quinidine, procainamide, disopyramide

Question 23

Class Ib drugs: Na+ channel blockers

Answer 23

Class IB lidocaine, mexiletine, phenytoin

Question 24

Class Ic drugs: Na+ channel blockers

Answer 24

Class IC propafenone, flecainide, encainide

Question 25

All class I drugs show

Answer 25

↑refractory period
↓ conduction velocity
↓re-entry

Question 26

Re-entry can be defeated by either:

Answer 26

slowed conduction velocity or longer refractory period

Question 27

Class Ib drugs show pure class I action:

Answer 27

slow upstroke, decreased AP duration

Question 28

Class Ia & Class Ic drugs delay phase 3 onset via________

Answer 28

K+ channel block

Question 29

Class 1a has a prolonged

Answer 29

repolarization

Question 30

Two conditions are required for re-entry:

Answer 30

(1) have unidirectional conduction block in any kind of functional circuit
(2) the conduction time around the circuit > refractory period

Question 31

Re-entry could be terminated by:

Answer 31

(1) converting uni- to bi-directional block

(2) or by prolonging refractory time

Question 32

Prolonged refractoriness can suppress re-entrant arrhythmias because:

Answer 32

• refractory tissue will not generate an action potential

* and so the re-entrant wave of excitation is extinguished

Question 33

Class II drugs (β-adrenergic receptor blockers) CURRENT

Answer 33

↓ If current
↓ L-type Ca2+ current
↓ K+ current

Question 34

β-blockers are consequently used to terminate arrhythmias that involve AV
nodal re-entry, and in controlling ventricular rate during _______

Answer 34

atrial fibrillation.

Question 35

Class II drugs (β-adrenergic receptor blockers) RESULTS

Answer 35

↓ rate of diastolic depolarization in pacing cells

↓ upstroke rate, and slows repolarization, particularly in AV nodal myocytes

Question 36

Adenosine-induced changes in membrane currents:

Answer 36

↓ SA node and AV node firing rate

↓ conduction rate in the AV node