Pharm Exam 4 (Antiarrhythmic Drugs)

Front 1

1) Arrhythmias may result in:

Back 1

a) Decrease in cardiac output
b) Tissue ischemia
c) Syncope
d) Sudden death

Front 2

1) In general pts experiencing an arrhythmia may have a varying degree of symptoms

Back 2

a) Asymptomatic
b) Mildly symptomatic (palpitations)
c) Moderately symptomatic (weak or heart failure)
d) Highly symptomatic (loss of consciousness or sudden death)

Front 3

1) Antiarrhythmic drugs may be life saving in a pt experiencing what degree of symptoms?

Back 3

a) moderately to highly symptomatic pts

Front 4

1) Review of resting membrane potential

Back 4

a) The membrane potential of the cardiac cells is determined by the concentration of Na+, K+, and Ca+ on either side of the membrane
b) These ions move across the membrane in response to Electrico-Chemical gradient
c) The typical cardiac cell resting membrane potential is ~80-95 mV
• Maintained by the NA/k ATPase and K+ channels
d) Inward rectifier K+ channels are open at negative transmembrane potentials (late phase 3&4)
• As a consequence, K+ can move across the resting membrane in response to the electrochemical gradient
• The concentration gradient is slightly > than the Electrical gradient at rest
e) Channel Level
• Closed --> Open --> Inactivated --> Closed
• The inactivated channels cannot open
f) Tissue level
• Excitable --> Excited --> Refractory --> excitable
• Refractory means that there is to many channels inactivated to depolarize

Front 5

1) Increased Automaticity (of the SA node) can be caused by:

Back 5

a) any change that decreases the time required for depolarization from the maximal diastolic potential to the threshold potential.
b) Increased automaticity occurs if the rate of diastolic depolarization (the slope of phase 4) in the SA node or in the latent pace maker is increased
c) **there is no resting membrane potential of the SA node…it just drifts positive until it reaches the threshold to create an action potential

Front 6

1) Early After Depolarization (EAD) – are induced by

Back 6

a) bradycardia (spread out QT interval)

Front 7

1) Late After Depolarization (LAD)(aka DAD) – are induced by

Back 7

a) tachycardia (shortened QT interval)
• Ca+ overload can lead to LAD

Front 8

1) 3 Necessary events for Re-entry to occur

Back 8

a) Obstacle to normal Action Potential Conduction
b) Unidirectional Block
c) Conduction time must exceed refractory period

Front 9

1) Reentry is characterized by :

Back 9

a) the retrograde conduction of impulse into previously depolarized tissue
b) It is usually characterized by the presence of a unidirectional conduction block in a bifurcating conduction pathway

Front 10

1) Reentry In Ventricular Tissue,

Back 10

a) the unidirectional block is often caused by decremental conduction of the impulse in the anterograde direction, with normal conduction of the impulse in the retrograde direction

Front 11

1) Reentry in the AV node

Back 11

a) is the most common electrophysiologic mechanism responsible for PSVT.
b) Reentry occurs when a premature atrial depolarization arrives at the AV node and finds that one pathway(B) is still refractory from the previous depolarization. The other pathway(a) however is able to conduct the impulse to the ventricle. Retrograde conduction of the impulse through pathway (B) leads to reentry of the atrium and results in tachycardia. In the AV node, the unidirectional block results from the (B) pathways longer refractory period, which blocks anterograde conduction but permits retrograde conduction after it has recovered its excitability
• The distal common pathway is still refractory so this has very little effect on the ventricles

Front 12

1) In general, antiarrhythmic drugs can:

Back 12

a) Decrease automaticity of ectopic pace makers
b) Reduce conduction and excitability more in depolarized tissue than in normal tissue
c) Increase the refractory period to a greater extent in depolarized tissue than in normal tissue

Front 13

1) Mechanisms of available drugs

Back 13

a) Class I = Block Na+ channels
• Broken down into 1a, ab, and 1C
b) Class II = Block sympathetic autonomic effects on the heart (BB)
c) Class III = Prolong the refractory period
• by prolonging the action potential,
• usually by K+ channel blockers
d) Class IV = Block Ca+ channels (CCB)
e) Others = digoxin, adenosine, Magnesium sulfate

Front 14

1) Steps in the management of atrial flutter / fibrillation and paroxysmal supraventricular tachycardia (PSVT)

Back 14

a) Step 1
• Carotid sinus massage / valsalva maneuver
b) Steps 2,3,4 (Can be used in any order)
• Drugs to slow ventricular rate
(1) -----Esmolol
(2) -----CCB
(3) -----Digoxin
(4) -----Adenosine
• Drugs to convert atrial rhythm
(1) -----Ibutilide
(2) -----Defetilide
(3) -----Soralol
• Electroversion (shock them) if drugs don’t work, or as 1st choice

c) Step 5
• Long term management
(1) -----Amiodarone
(2) -----Sotalol
(3) -----Flecainide
d) Step 6
• Catheter
• surgical oblation
• Pacemaker

Front 15

1) Steps in the management of ventricular arrhythmias

Back 15

a) Steps 1 &2 (in any order)
• Drugs to convert rhythm
(1) -----Amiodarone (possibly with epinephrine)
(2) -----Procainamide
• Electricoconversion (shock them) if the drugs don’t work or as 1st choice
b) Step 3
• Long term management
(1) -----Amiodarone
(2) -----Sotalol
(3) -----Flecainide
c) Step 4
• Catheter
• Surgical oblation
• Pacemaker
-----Implantable cardioverter –defibulator

Front 16

1) What drugs are included in class 1A

Back 16

a) Quinidine
b) Dispyramide
c) Procainamide

Front 17

1) What drugs are included in class 1B

Back 17

a) Lidocaine
b) Mexiletine
c) Tocainide

Front 18

1) What drugs are included in class 1C

Back 18

a) Flecainide
b) Propafenone

Front 19

1) What drugs are included in class II

Back 19

a) BB
• Esmolol
• Propranlol
• Metoprolol
• Carvedilol

Front 20

1) What drugs are included in class III

Back 20

a) Amiodarone
b) Dofetilide
c) Ibutilide
d) Sotalol

Front 21

1) What drugs are included in class IV

Back 21

a) Non- dihydropyridine Ca+ channel blockers
• Verapamil
• Diltiazem

Front 22

1) What “other” drugs are used as antiarrhythmics? (not in a class)

Back 22

a) Adenosine
b) Digoxin
c) Magnesium Sulfate

Front 23

1) MOA of Quinidine

Back 23

a) Block Na+ Channels
• Has the highest affinity for the Na+ channel when it is open

Front 24

1) Characteristic of class 1A

Back 24

a) Decrease ectopic automaticity of the AV node
b) Prolongs QRS duration
• By slowing phase 0 depolarization
c) Prolongs QT interval
• By slowing phase 3 repolarization
d) Rate of disassociation = Slow
• The slower it disassociates the more it affects HR
e) Therefore class 1A slows conduction and increases refractory periods, thereby increasing the QRS duration and the QT interval. They are primarily used for the long term suppression of arrhythmias

Front 25

1) DOA of Quinidine

Back 25

a) 7 hours

Front 26

1) Elimination half life of Quinidine

Back 26

a) 6 hours

Front 27

1) Can Quinidine be used during pregnancy?

Back 27

a) yes

Front 28

1) Adverse effects of Quinidine

Back 28

a) Cardiac
• Leads to normal sinus rhythm but 2-3x increase in mortality
• Can cause torsade de pointes
• Not used frequently
b) Non cardiac
• Diarrhea
• Nausea
• Vomiting
• Headache
• Dizziness
• Tinnitus
c) Drug interactions
• Increases digoxin plasma levels (possibility for digoxin toxicity)

Front 29

1) MOA of Dispyramide

Back 29

a) Block Na+ Channels
• Has the highest affinity for the Na+ channel when it is open

Front 30

1) DOA of Dispyramide

Back 30

a) 6 hours

Front 31

1) Elimination half life of Dispyramide

Back 31

a) 7 hours

Front 32

1) MOA of Procainamide

Back 32

a) Block Na+ Channels
• Has the highest affinity for the Na+ channel when it is open

Front 33

1) DOA of Procainamide

Back 33

a) 5 hours

Front 34

1) Elimination half life of Procainamide

Back 34

a) 3.5 hours

Front 35

1) Adverse Effects of Procainamide

Back 35

a) Cardiac (Similar to quinidine)
• Leads to normal sinus rhythm but 2-3x increase in mortality
• Can cause torsade de pointes
• Not used frequently
b) Non cardiac
• Long term use can lead to a Lupus erythematosus like syndrome (in 1/3 patients)
(1) -----Characterized by arthralgia and arthritis, pleuritis, and pericarditis
c) Not typically a first choice drug

Front 36

1) Can Procainamide be used during pregnancy?

Back 36

a) It Can be used Acutely during pregnancy

Front 37

1) MOA of Lidocaine

Back 37

a) Block Na+ Channels
• Has the highest affinity for the Na+ channel when it is Inactivated

Front 38

1) Characteristic of class 1B

Back 38

a) Decrease ectopic automaticity of the AV node
b) No change in QRS duration
c) No change / Decrease QT interval
• Has little effect on cardiac tissue but it can accelerate phase 3 repolarization (decreasing QT interval slightly)
d) Rate of disassociation = Rapid
• The slower it disassociates the more it affects HR
e) They have little effect on normal cardiac tissue and ECG findings, but they can decrease the QT interval slightly.

Front 39

1) ROA Lidocaine

Back 39

a) Only IV
• Lidocaine has to be administered IV for the Tx of acute ventricular arrhythmias (not first choice drug)

Front 40

1) Elimination half life of Lidocaine

Back 40

a) 1.5 hours

Front 41

1) Adverse effects of Lidocaine

Back 41

a) Cardiac
• Relatively few side effects compared to class I drugs
• May worsen ventricular arrhythmias in some patients
b) Non cardiac
• Parasthesias (pin and needle sensation)
• Tremor
• Nausea
• Lightheadedness
• Slurred speech
c) Convulsions

Front 42

1) MOA of Mexiletine

Back 42

a) Block Na+ Channels
• Has the highest affinity for the Na+ channel when it is Inactivated

Front 43

1) Clinical use of Mexiletine

Back 43

a) Mexiletine and Tocainide, oral congeners of lidocaine, have been used for long term prophylaxis

Front 44

1) DOA of Mexiletine

Back 44

a) 10 hours

Front 45

1) Elimination half life of Mexiletine

Back 45

a) 11 hours

Front 46

1) Adverse effects of Mexiletine

Back 46

a) Cardiac
• Relatively few side effects compared to class I drugs
• May worsen ventricular arrhythmias in some patients
b) Non cardiac
• Parasthesias (pin and needle sensation)
• Tremor
• Nausea
• Lightheadedness
• Slurred speech
c) Convulsions

Front 47

1) MOA of Tocainide

Back 47

a) Block Na+ Channels
• Has the highest affinity for the Na+ channel when it is Inactivated

Front 48

1) Clinical use of Tocainide

Back 48

a) Mexiletine and Tocainide, oral congeners of lidocaine, have been used for long term prophylaxis

Front 49

1) DOA of Tocainide

Back 49

a) 12 hours

Front 50

1) Elimination half life of Tocainide

Back 50

a) 12 hours

Front 51

1) Adverse effects of Tocainide

Back 51

a) Cardiac
• Relatively few side effects compared to class I drugs
• May worsen ventricular arrhythmias in some patients
b) Non cardiac
• Parasthesias (pin and needle sensation)
• Tremor
• Nausea
• Lightheadedness
• Slurred speech
• Convulsions
c) ***Tocainide can cause agranulocytosis (can lead to hospitalization style pneumonia)

Front 52

1) MOA of Flecainide

Back 52

a) Block Na+ Channels
• Has the highest affinity for the Na+ channel when it is open

Front 53

1) Characteristic of class 1C

Back 53

a) Decrease ectopic automaticity of the AV node
b) Prolongs QRS duration (markedly increased)
• Has the greatest effect on slowing phase 0 depolarization
c) Prolongs QT interval (some but not much)
• Slows phase 3 repolarization
d) Rate of disassociation = Very Slow
• The slower it disassociates the more it affects HR
e) They have greater effect than other Na+ channel blockers on cardiac conduction but have little effect on the action potential duration

Front 54

1) Flecainide and propafenone are used to tx _______________

Back 54

a) supraventricular arrhythmias and life threatening arrhythmias

Front 55

1) DOA of Flecainide

Back 55

a) 21 hours

Front 56

1) Elimination half life of Flecainide

Back 56

a) 14 hours

Front 57

1) Adverse Effects of Flecainide

Back 57

a) bronchospasm
b) seizure

Front 58

1) Can Flecainide be used during pregnancy?

Back 58

a) Flecainide can be used during pregnancy and is a 1st line choice for fetal SVT

Front 59

1) MOA of Propafenone

Back 59

a) Block Na+ Channels
b) Has the highest affinity for the Na+ channel when it is open

Front 60

1) DOA of Propafenone

Back 60

a) 10 hours

Front 61

1) Elimination Half Life of Propafenone

Back 61

a) 6 hours

Front 62

1) Adverse effects of Propafenone

Back 62

a) Agranulocytosis
b) Anemia

Front 63

1) Which BB can be used as antiarrhythmics?

Back 63

a) Esmolol
b) Propranlol
c) Metoprolol
d) Carvedilol

Front 64

1) Class II specific information

Back 64

a) Beta blockers
b) Used to tx supraventricular and ventricular arrhythmias
c) Reduce sudden death in myocardial infarction
d) The only drugs that reduce mortality in asymptomatic patients (or not increase mortality rate)
e) Class II and class Iv drugs slow phase 5 depolarization in the SA node and increase the PP interval. They also slow the AV node conduction velocity and increase the PR interval.
• Decrease HR (PRIMARY EFFECT)
• Increase PR interval
• No change in QRS or QT interval

Front 65

1) MOA of Amiodarone

Back 65

a) Blocks K+ channels (slowing repolarization)
• Enhancing inward currents (e.g. Na+)

Front 66

1) Class III specific information

Back 66

a) Prolong Action potential duration
b) Increases QT interval
• Markedly prolong phase 3
• They have no effect on phase 0 – therefore they do not change the QRS interval

Front 67

1) Electricophysical properties of Amiodarone

Back 67

a) Increase refractory period of AV node
b) Increase refractory period of the His purkinje system and ventricle
c) **Increase the PR interval
d) Increase the QT interval
e) Potent inhibitor of abnormal automaticity

Front 68

1) Onset of action of Amiodarone

Back 68

a) 2 weeks

Front 69

1) DOA of Amiodarone

Back 69

a) 4 weeks

Front 70

1) Elimination half life of Amiodarone

Back 70

a) 40 days

Front 71

1) Amiodarone has _______class activity

Back 71

a) class I, II, III, and IV
• Its biggest effect is on class III activity

Front 72

1) Therapeutic uses of Amiodarone

Back 72

a) Avoid during pregnancy
b) Oral for long term suppression of atrial and ventricular arrhythmias
c) IV administration for terminating acute ventricular arrhythmias
d) This is one of the few drugs that prolongs QT interval w/o triggering torsade

Front 73

1) Adverse effects of Amiodarone

Back 73

a) Blue gray skin discoloration
b) Thyroid abnormalities
• Both hyper and hypo
c) Neurological effects
• Parasthesias
• Tremor
• Ataxia
• Headaches
d) Pulmonary fibrosis
• Cough
• Dyspnea
• Decreased CO2 diffusion

Front 74

1) Drug interactions of Amiodarone

Back 74

a) Decreased clearance of many drugs
• Warfarin
• Quinidine
• Procainamide
• Flecainide
• Digoxin (digoxin toxicity)

Front 75

1) MOA of Dofetilide

Back 75

a) Blocks K+ channels (slowing repolarization)
• Potent blocker of Ikr
• Enhancing inward currents (e.g. Na+)

Front 76

1) Electricophysical properties of Dofetilide

Back 76

a) Increase refractory period of AV node
b) Increase refractory period of the His purkinje system and ventricle
c) ***No change in the PR interval
d) Increase the QT interval

Front 77

1) Onset of action of Dofetilide

Back 77

a) 1 hour

Front 78

1) DOA of Dofetilide

Back 78

a) 12 hours

Front 79

1) Elimination half life of Dofetilide

Back 79

a) 10 hours

Front 80

1) Clinical use of Dofetilide

Back 80

a) Potent blocker of Ikr that is used to maintain sinus rhythm after cardioversion of atrial fibrillation or flutter
b) Increases QT interval
• Dose must be titrated to avoid excess QT interval prolongation
c) Can cause torsade de pointes

Front 81

1) MOA of Ibutilide

Back 81

a) Blocks K+ channels (slowing repolarization)
• Enhancing inward currents (e.g. Na+)

Front 82

1) Electricophysical properties of Ibutilide

Back 82

a) Increase refractory period of AV node
b) Increase refractory period of the His purkinje system and ventricle
c) ***No change / Increase the PR interval
d) Increase the QT interval

Front 83

1) Onset of action of Ibutilide

Back 83

a) 5 min

Front 84

1) DOA of Ibutilide

Back 84

a) N/A
b) IV only

Front 85

1) Elimination half life of Ibutilide

Back 85

a) = 6 hours

Front 86

1) Can Ibutilide be used during pregnancy?

Back 86

a) Avoid during pregnancy

Front 87

1) Clinical use of Ibutilide

Back 87

a) Use IV to convert pts with atrial flutter or fibrillations to normal sinus rhythm
b) Slows repolarization and prolongs cardiac action potentials
c) Can cause torsade de pointes

Front 88

1) MOA of Sotalol

Back 88

a) Blocks K+ channels (slowing repolarization)
• Enhancing inward currents (e.g. Na+)

Front 89

1) Sotalol belongs to what class of antiarrhythmics?

Back 89

a) This drug has both Class II activity ( beta blocking) and Class III activity
• He mentions it in the class III section though
• Slows repolarization and prolongs action potential

Front 90

1) Electricophysical properties of Sotalol

Back 90

a) Increase refractory period of AV node
b) Increase refractory period of the His purkinje system and ventricle
c) ***Increase the PR interval
d) Increase the QT interval

Front 91

1) Onset of action of Sotalol

Back 91

a) 2 hour

Front 92

1) DOA of Sotalol

Back 92

a) 15 hours

Front 93

1) Elimination half life of Sotalol

Back 93

a) 12 hours

Front 94

1) Clinical use of Sotalol

Back 94

a) Used for chronic suppression of supracentricular and ventricular arrhythmias
b) Can cause torsade de pointes
c) Can cause bronchospasm (therefore it has some B2 blocking activity as well)

Front 95

1) What Non- dihydropyridine Ca+ channel blockers are used as antiarrhythmics?

Back 95

a) Verapamil
b) Diltiazem

Front 96

1) Non- dihydropyridine Ca+ channel blockers are used to treat what types of arrhythmias?

Back 96

a) Treats reentrant supraventricular tachycardia
b) It also protect the ventricles in atrial flutter and fibrillations

Front 97

1) Of the 2 CCB used for antiarrhythmics which one is preferred for pregnancy?

Back 97

a) verapamil is preferred during pregnancy

Front 98

1) Onset of action, DOA, and elimination half life for verapamil

Back 98

a) Onset of action of = 2 hours
b) DOA = 9 hours
c) Elimination half life = 5 hours

Front 99

1) Specific electrophysiologic properties for Class IV drugs

Back 99

a) Decrease automaticity of the AV node
b) Decrease conduction velocity in the AV node
c) Increase refractory period in the AV node
• Thereby terminating the AV node reentry that is responsible for the supraventricular tachycardia
d) Decrease HR
e) Increase PR interval
• By slowing the AV node conduction velocity
f) No change in QRS or QT
g) Slow phase 4 depolarization markedly prolonging the PP interval

Front 100

1) Onset of action, DOA, and elimination half life for Diltiazem

Back 100

a) Onset of action = 2 hours
b) DOA = 8 hours
c) Elimination half life = 5 hours

Front 101

1) What are the 3 “other” drugs used as antiarrhythmics?

Back 101

a) Adenosine
b) Digoxin
c) Magnesium Sulfate

Front 102

1) Effects of Adenosine on the ECG

Back 102

a) Increase HR
b) Increase PR interval
c) No effect on QRS or QT

Front 103

1) ROA of Adenosine

Back 103

a) IV only

Front 104

1) Onset of action, DOA, and elimination half life of Adenosine

Back 104

a) Onset of action = 30 seconds
b) DOA = 1.5 min
c) Elimination half life = <10 seconds

Front 105

1) Does adenosine get excreted in the urine?

Back 105

a) Does not get excreted…it is used up in the cells to make ATP

Front 106

1) Clinical use of Adenosine

Back 106

a) Administered as a rapid IV bolus to terminate acute supraventricular tachycardia
b) Increases refractory period of AV node
c) DOC for prompt conversion of paroxysmal supraventricular tachycardia
d) Can use during pregnancy

Front 107

1) Adverse effects of Adenosine

Back 107

a) They go away quickly
• Flushing
• Bronchospasm
• Headache
• Hypotension
• Nausea

Front 108

1) MOA of Digoxin

Back 108

a) Inhibits Na/K ATPase  increased K+ efflux

Front 109

1) Cardiac effects of Digoxin

Back 109

a) Positive ionotropic and negative chronotropic effect (doesn’t cause bradycardia like BB)

Front 110

1) Can Digoxin be used during pregnancy?

Back 110

a) Can use drug during pregnancy

Front 111

1) Effects of Digoxin on the ECG

Back 111

a) Decrease HR
b) Increase PR interval
c) No effect on QRS
d) ***Decrease QT

Front 112

1) Onset of action, DOA, and elimination half life of Digoxin

Back 112

a) Onset of action = 1 hour
b) DOA= 24 hours
c) Elimination half life = 35 hours

Front 113

1) Effects of Magnesium Sulfate on the ECG

Back 113

a) No effect on HR
b) No effect on PR
c) No effect on QRS
d) No effect on QT

Front 114

1) ROA of Magnesium Sulfate

Back 114

a) IV only

Front 115

1) Onset of action of Magnesium Sulfate

Back 115

a) <5 min

Front 116

1) Is Magnesium Sulfate excreted in the urine?

Back 116

a) 100% of the excess is excreted away in the urine

Front 117

1) Clinical use of Magnesium Sulfate

Back 117

a) Given IV to suppress drug induced arrhythmias