Anti-arrhythmic Drugs

Question 1

Where are fast response cells in the heart?

Answer 1

atria, ventricle, his-purkinje

Question 2

Where are slow response cells in the heart?

Answer 2

SA and AV nodes

Question 3

What is the major ion involved in depolarization of fast cells?

Answer 3

Na

Question 4

What is the major ion involved in depolarization of slow cells?

Answer 4

Ca

Question 5

What class inhibits depolarization of fast cells?

Answer 5

class 1 sodium channel blockers

Question 6

What class inhibits depolarization of slow cells?

Answer 6

class 4 calcium-entry blockers

Question 7

What are the 3 important differences between fast and slow response cells?

Answer 7

1. Diastolic Depolarization-slow response cells usually
2. Membrane Responsiveness - level of resting membrane potential determines maximum upstroke or conduction velocity (mV/msec) of the AP
3. Effective Refractory Period (ERP)-minimum interval between two propagating impulses

Question 8

What are the 3 main mechanisms of arrhythmias?

Answer 8

• Increased automaticity (inappropriately excitable cells)
• Triggered automaticity (normal action potential is interrupted or followed by an abnormal)
• Reentry (abnormal impulse conduction)

Question 9

What is early afterdepolarization (EAD)?

Answer 9

type of triggered automaticity that interrupts repolarization and is exacerbated by slow rate-long QT syndrome (Torsades de Pointes results)

Question 10

What is delayed or late afterdepolarization (DAD)?

Answer 10

type of triggered automaticity that occurs after repolarization and is exacerbated by fast rates, high
intracellular Ca2+

Question 11

What can trigger DAD?

Answer 11

Digitalis toxicity, catecholamines (NE, EPI) and ischemia

Question 12

What are the 4 ways anti-arrhythmic drugs reduce spontaneous discharge in autonomic tissues?

Answer 12

decrease phase 4 slope
increase maximum diastolic potential
increase threshold potential
increased action potential duration

Question 13

What are the 4 classes of anti-arrhythmic drugs?

Answer 13

1 sodium channel blockers
2 beta-adrenergic blockers
3 K channel blockers
4 Calcium channel blockers

Question 14

What are the 3 subclasses of class 1 (Na blockers)?

Answer 14

1A prolong repolarization: moderate depress phase 0 and slow conduction
1B shorten repolarization: little depress phase 0 and slow conduction
1C little effect on repolarization: marked phase 0 depress and slow condution

Question 15

What class acts on fast response cells, reduce membrane responsivness, increase threshold, reduce Vmax, and prolong refractory period?

Answer 15

Class 1: Na channel blockers

Question 16

Class 1A drug?

Answer 16

Quinidine

Question 17

Direct effects of quinidine?

Answer 17

Increase AP threshold
decrease Vmax
increase ERP (effective refractory period)

Question 18

Indirect effects of quinidine?

Answer 18

Blocks K+ channels  early afterdepolarizations (EADs) & Vagolytic Effect

Question 19

Use of quinidine?

Answer 19

• Atrial flutter or fibrillation

- Prevent ventricular tachycardia and fibrillation

Question 20

Major side effects of quinidine?

Answer 20

Severe GI effects - Diarrhea, cramps
 Heart – vagolytic
 Inhibits P450 system (metabolism of narcotics is reduced)
 Proarrhythmic – not necessarily related to the arrhythmia being treated.
 Reduces the renal clearance of digitalis; increases plasma levels of digitalis

Question 21

Is quinidine okay for pt with renal failure?

Answer 21

Yes, metabolized in liver.

Question 22

Class 1B drug?

Answer 22

Lidocaine

Question 23

Direct effects of lidocaine?

Answer 23

• Increase AP threshold
• Increased Block of Na+ channels ( Vmax) at high HR and in depolarized cells
• decreased AP duration and ERP

Question 24

Side effects of lidocaine?

Answer 24

dizziness & seizures

Question 25

What is lidocaine used for?

Answer 25

Ventricular tachycardia Digitalis induced arrhythmias Safe for patients with Long QT Syndrome

Question 26

What is a class 1C drug?

Answer 26

Flecainide

Question 27

What are the direct effects of flecainide?

Answer 27

``` Increase AP threshold decreased Vmax (conduction velocity) Variable effects on ERP dissociates from Na+ channel slowly makes it the most potent Na channel blocker ```

Question 28

Side effects of flecainide?

Answer 28

pro-arrhythmic

Question 29

What is flecainide used for?

Answer 29

Approved for used in life-threatening situations when supraventricular and ventricular arrhythmias are resistant to other drugs

Question 30

What kind of drugs are class 2?

Answer 30

beta-blockers

Question 31

How do beta-blockers work?

Answer 31

Bind to ß-adrenergic receptors on cardiac cell membranes to competitively inhibit epinephrine and norepinephrine binding which antagonizes SNS stimulation

Question 32

What effect to beta-blockers have on the AP curve?

Answer 32

slow the rate of diastolic (phase 4) depolarization.

Question 33

What are the two beta-blockers we have to know?

Answer 33

propranolol and esmolol

Question 34

What is the difference between propranolol and esmolol?

Answer 34

Propranolol – Long acting blocker (oral) | Esmolol – Short acting blocker (IV)

Question 35

What are beta-blockers used for?

Answer 35

Used for all atrial arrhythmias, ventricular tachycardia and fibrillation

Question 36

Are beta-blockers safe?

Answer 36

The beta blockers are currently the most useful antiarrhythmic drugs available due to their safety record and wide clinical applications

Question 37

Are beta-blockers safe for people with long QT syndrome?

Answer 37

Yes, beta-blockers do not prolong repolarization in ventricular tissues

Question 38

What are the major side effects of beta-blockers?

Answer 38

negative inotropic effect, heart block, bradycardia and bronchospasm

Question 39

In general, what kind of drugs are class 3?

Answer 39

K channel blockers

Question 40

What are the common effects of K channel blockers?

Answer 40

Main common property is K+ channel block; prolongs action potential repolarization (action potential duration increases); reverse use-dependence.

Question 41

What are the two K channel blockers we have to know?

Answer 41

Amiodarone & sotalol

Question 42

Which K channel do most blocker drugs target?

Answer 42

most common target is IKr (hERG channel)

Question 43

Amiodarone has multiple mechanisms of action. What are they?

Answer 43

Potent K+ channel blocker (blocks both IKr and IKs)  Modest Na+ channel blocker  Modest Ca++ channel blocker  Modest beta- adrenoreceptor blocker

Question 44

What is amiodarone used for?

Answer 44

 Effective against ventricular tachyarrhythmias and fibrillation.  Also used in the prevention of recurrent paroxysmal atrial fibrillation or flutter

Question 45

What are the major side effects of amiodarone?

Answer 45

 Triggered arrhythmias (EADs); but rarely associated with Torsades de Pointes  Altered thyroid function (inhibits conversion of T4 to T3) - hypothyroidism  Pulmonary fibrosis – often irreversible

Question 46

What is sotalol's MOA?

Answer 46

Major action is block of K+ channel (IKr) also has beta-adrenergic receptor blocking actions (secondary effect)

Question 47

What side effect do we have to watch out for with sotalol?

Answer 47

triggered arrhythmias with Torsades de Pointes.

Question 48

What is sotalol used for?

Answer 48

Effective against ventricular tachyarrhythmias and fibrillation. Also used against supraventricular tachycardias, atrial fibrillation

Question 49

Torsades de Pointes in pt with sotalol produces what changes in the EKG?

Answer 49

long QT interval prominent U wave d/t prolonged repolarization post-ectopic pause

Question 50

What do class 4 drugs do?

Answer 50

Ca channel blockers

Question 51

Where to Ca channel blockers primarily block?

Answer 51

Acts primarily on slow response cells (SA & AV node), which are dependent on Ca++ influx for action potential depolarization

Question 52

What are the major effects of Ca channel blockers on the heart?

Answer 52

Increase threshold for AP firing in nodal cells  Increase nodal cell refractory period  Depress conduction velocity in the SA and AV nodes

Question 53

What are Ca channel blockers used to treat?

Answer 53

Paroxysmal supraventricular tachycardia

Question 54

What are major side effects of Ca channel blockers?

Answer 54

- -Negative chronotropic effect – decreases automaticity of SA node (bradycardia) - -Negative inotropic effect – decreases Ca++ influx during plateau phase of ventricular action potential - -Hypotension – decreases Ca++ influx into vascular smooth muscle cells

Question 55

What Ca channel blockers should we know?

Answer 55

nifedipine verapamil diltizaem

Question 56

Which Ca channel blocker has the side effect of peripheral edema?

Answer 56

nifedipine

Question 57

Which Ca channel blocker especially has the side effect of constipation?

Answer 57

verapamil

Question 58

Which Ca channel blocker has the side effect of interacts with digitalis to slow conduction velocity in the AV node causing heart block?

Answer 58

verapamil | diltizaem

Question 59

Which Ca channel blocker has the side effect of increasing plasma levels of digitalis by competing for renal excretion?

Answer 59

verapamil | diltizaem

Question 60

What is adenosine's MOA?

Answer 60

Very rapidly activates K+ channels to slow phase 4 depolarization at AV node (T1/2=10 seconds)  Blocks cAMP-enhanced Ca2+ channel activity at the AV node

Question 61

What should you use adenosine for?

Answer 61

Indicated for supraventricular tachycardia-slows AV conduction and heart rate

Question 62

How does Digoxin work?

Answer 62

Enhances vagal parasympathetic activity to slow conduction at the AV node

Question 63

What should you use digoxin for?

Answer 63

Indicated for atrial fibrillation and supraventricular tachycardia to control ventricular response rate