Antiarrhythmic Drugs

Question 0

What beta receptor(s) does Propranolol block?

Answer 0

ß-1 and ß-2

Question 1

What is the ULTRA-short acting beta blocker?

Answer 1

Esmolol

Question 2

What drug is a non-selective β-AR antagonist; however, it is classified as a Class III agent due to its profound ability to prolong the action potential (Potassium channel blocker)?

Answer 2

Sotolol

Question 3

What problems can occur because amiodarone blocks alpha-1 receptors?

Answer 3

decreased bp

increased risk of hypotension

Question 4

What is the dosing of oral amiodarone?

Answer 4

1g/day (divided doses) over 2 weeks, then 200-400 mg/day

Question 6

What is the dosing of IV amiodarone?

Answer 6

for the acute treatment of ventricular arrhythmias: give 150 mg IV bolus, followed by 1mg/min x 6 hours, then 0.5 mg/min x 18 hours, then typically followed by 200 mg/day oral starting dose

Question 7

What class primarily affects myocytes and purkinje fibers?

Answer 7

Class I agents (Na+ channel blockers)

Question 8

Class I agents are essentially “____________”

Answer 8

local anesthetics

Question 9

In normal tissue, VGNC spend most of their time in their _________ state.
A. resting
B. inactive
C. active

Answer 9

A. resting

Question 10

In arrhythmic tissue, VGNC spend most of their time in their _________ state.
A. resting
B. inactive
C. active

Answer 10

B & C (not resting very much)

Question 11

What state(s) do Na+ channel blockers bind to?

Answer 11

Active and inactive (phase 0-3)

Question 12

When do Na+ channel blockers dissociate from the channel?

Answer 12

when the channel enters the resting state

Question 13

Class Ia Agents have a Tau-recovery time of:
A. 10 sec
B. 1-10 sec
C. <1 seconds

Answer 13

B. intermediate (1-10 sec)

Question 14

Class Ib Agents have a Tau-recovery time of:
A. 10 sec
B. 1-10 sec
C. <1 seconds

Answer 14

C. rapid (< 1 sec)

Question 15

Class Ic Agents have a Tau-recovery time of:
A. >10 sec
B. 1-10 sec
C. <1 seconds

Answer 15

D. delayed (> 10 sec)

Question 16

What is Tau-recovery time?

Answer 16

Tau-recovery time: the time it takes for the drug to dissociate from the VGNC once the channel enters the resting state.

Question 17

Tau-recovery time ________ relates to the magnitude in which agents in each subclass affect the slope of Phase 0 of the cardiac myocyte action potential (AP)
A. directly
B. indirectly

Answer 17

A. DIRECTLY

Question 18

Since Class Ic agents take a longer time to come off the VGNC, if they bind to normal tissue (not desired, but can happen) the drug can be _________

Answer 18

“PRO-ARRHYTHROGENIC.”

Question 19

Which of the following are Class 1A agents?
A. Quinidine
B. Mexiletine
C. Disopyramide
D. Procainamide

Answer 19

A,C,D

Question 20

Which of the following are Class 1B agents?
A. Quinidine
B. Mexiletine
C. Lidocaine
D. Propafenone

Answer 20

B, C

Question 21

Which of the following are Class 1C agents?
A. Flecainide
B. Mexiletine
C. Lidocaine
D. Propafenone

Answer 21

A,D

Question 22

Which class IA agent has class I and III action?

Answer 22

Quinidine

Question 23

Which class IA agent can reduce digoxin clearance by 50%?

Answer 23

Quinidine

Question 24

What are the adverse effects of Quinidine?

Answer 24

GI (30-50%) mostly diarrhea
Cinchonism*
Antimuscarinic effects
hypotension

Question 25

What is Cinchonism?

Answer 25

headaches, dizziness, ringing in ears

Question 26

``` Which class IB agent binds to α-1 acid Glycoprotein and why is this important to know? ```

Answer 26

Lidocaine Alpha-1 acid glycoprotein is elevated during stress or injury such as MI, post-MI or post-op (“acute phase protein”) So, Free fraction of lidocaine may change during the course of therapy as the pt transitions from post-acute MI to a more stable condition.

Question 27

Lidocaine is a very effective Na+ channel blocker, so why do we not use it for prophylaxis?

Answer 27

evidence now shows this increases mortality

Question 28

When is Lidocaine used?

Answer 28

It is very effective at STOPPING Ventricular tachycardia (V-tach) in the acute post-MI setting

Question 29

What does Mexiletine usually treat?

Answer 29

peripheral neuropathies

Question 30

What are the 2 Class IC agents?

Answer 30

Flecainide, Propafenone

Question 31

Flecainide and Propafenone are both metabolized by _____.

Answer 31

CYP2D6

Question 32

ADRs of Flecainide?

Answer 32

``` Blurred vision Dizziness Edema Abdominal pain Constipation Headache nausea & vomiting (10%) mild negative chronotropic effect (may exacerbate CHF) ```

Question 33

ADRs of Propafenone?

Answer 33

``` Mild→moderate negative inotropic effect Rare cases of elevated liver enzymes Common GI: N/V Constipation Anorexia Diarrhea xerostomia ```

Question 34

What do you monitor in Flecainide?

Answer 34

trough monitoring

Question 35

Contraindications with Flecainide?

Answer 35

Flecainide + Dofetilide (b/c of risk of developing pro-arrhythmias) Flecainide + Dronedarone (b/c dronedarone is a 2D6 inhibitor)

Question 36

Contraindications/Drug interactions with Proparenone?

Answer 36

CI: Propafenone + Dofetilide CI: patients with acute bronchospasm or asthma (BB activity) Interact with CYP2D6 inhibitors (Dronedarone, some SSRIs, delavirdine) May also interact with CYP1A2 & 3A4

Question 37

Tobacco smoke may ________ hepatic metabolism of Flecainide

Answer 37

increase

Question 38

Clearance of flecainide is _________ in pts with renal/hepatic insufficiency

Answer 38

decreased

Question 39

Which Class I agent can increase warfarin plasma levels?

Answer 39

Propafenone

Question 40

Is Propafenone protein bound?

Answer 40

Yes, 85-97% protein bound (primarily to alpha-1 acid glycoprotein)

Question 41

What CYP enzyme is Propafenone a substrate and inhibitor of?

Answer 41

CYP2D6 substrate and inhibitor (possibly)

Question 42

Which Class IC agent has weak BB activity?

Answer 42

Propafenone

Question 43

How are BB useful in treating arrhythmias?

Answer 43

Suppress SA nodal depolarization & AV nodal conduction which is useful in treating AF (atrial fibrillation)

Question 44

________ are effective at preventing & treating catecholamine-induced arrhythmias (SNS-induced arrhythmias) (ex. Pheochromocytoma)

Answer 44

BB

Question 45

What is a pheochromocytoma?

Answer 45

Pheochromocytoma: catecholamine secreting tumor in adrenal medulla

Question 46

Use BB with caution in patients with:

Answer 46

asthma/COPD or diabetes

Question 47

Which BB treats rapid, short-term control of supraventricular arrhythmias (ex. Sinus tachycardia, AF)?

Answer 47

esmolol

Question 48

What BB treats essential tremor?

Answer 48

Propranolol

Question 49

What BB has Membrane-stabilizing activity (local anesthetic action) may block Na+ channels in myocardial tissue (some class I properties)

Answer 49

Propranolol

Question 50

Which agents can prolong the QT interval?

Answer 50

Class III agents

Question 51

What is Torsades de Pointes?

Answer 51

Torsades de Pointes:“twisting of the points” is a condition that occurs when K+ channels are blocked and is deadly.

Question 52

Some class ___ agents may actually increase inward current (Ca2+ & Na+) to make the AP ore positive for a longer period of time. This causes delayed repolarization and therefore prolonged AP duration

Answer 52

class III agents

Question 53

Name 5 Class III agents:

Answer 53

1. AMIODARONE 2. Dronedarone 3. Sotolol 4. Ibutilide 5. Dofetilide

Question 54

What is the prototypical Class III agent?

Answer 54

AMIODARONE

Question 55

What is the analog of amiodarone | iodine groups are removed & methane-sufanomyl group is added → much less TH AEs

Answer 55

Dronedarone

Question 56

What is the MOA of amiodarone?

Answer 56

1. K+ channel blocker 2. Na+ channel blocker 3. ß-AR antagonist (BB) 4. CCB 5. Inhibition of cell-cell coupling (affects gap junctions) 6. TH & receptor effects (usually w/ chronic use) * has class I, II, III, & IV properties

Question 57

What does amiodarone treat?

Answer 57

wide variety of arrhythmias

Question 58

What is the half life of amiodarone?

Answer 58

Complex half-life Rapid: 3-10 days Slower: 50 days

Question 59

Is amiodarone lipophilic or hydrophilic?

Answer 59

Highly lipophilic (Accumulates in tissues)

Question 60

How is amiodarone metabolized?

Answer 60

CYP3A4

Question 61

What does amiodarone inhibit?

Answer 61

Pgp &CYP2C9 (increase warfarin plasma conc.)

Question 62

ADRs of amiodarone?

Answer 62

Pulmonary Fibrosis Thyroid Dysfunction Corneal Deposits Photodermatitis

Question 63

How long will elimination of amiodarone take once D'C?

Answer 63

MONTHS

Question 64

Which class III agent is a derivative of TH?

Answer 64

amiodarone

Question 65

Is dronedarone protein bound?

Answer 65

Yes 98% to albumin

Question 66

In which Class III agent, does BA increase with high fat meals?

Answer 66

Dronedarone

Question 67

Explain the PK properties of dronedarone with races and genders.

Answer 67

Pts > 65 YO have a 23% greater exposure to dronedarone Females have a 30% greater exposure than males Japanese males have a 2-fold higher exposure than Caucasian males

Question 68

When do you take dronedarone?

Answer 68

BID in morning and evening with meals

Question 69

Metabolism of dronedarone?

Answer 69

Metabolized by and inhibitor of CYP2D6 & 3A4

Question 70

ADRs of dronedarone?

Answer 70

N/V, diarrhea May worsen HF Skin & soft tissue rxns (rash, pruritus, eczema, atopic dermatitis)

Question 71

Can you take dronedarone while pregnant?

Answer 71

NO, pregnancy category X

Question 72

CI to dronedarone?

Answer 72

severe hepatic impairment | pregnancy

Question 73

What type of BB is stool?

Answer 73

non-selective (binds to ß-1 and ß-2)

Question 74

What drug has class II and III effects because it is a significant K+ blocker and prolongs QT interval?

Answer 74

Sotolol

Question 75

How is sotolol eliminated?

Answer 75

Eliminated almost 100% by kidneys

Question 76

ADRs of sotolol?

Answer 76

increased risk of TdP (b/c of QT prolongation) | generally well tolerated

Question 77

What class of agents Affect phase 2 of the cardiac myocyte AP (decreases Ca2+ entry & FOC) →negative inotropic effect (avoid in HF)

Answer 77

Class IV (CCBs)

Question 78

What are Class IV (CCB) Agents most useful in treating?

Answer 78

AF rate

Question 79

Use Class IV agents with caution in pts with:

Answer 79

Use with extreme CAUTION in pts with systolic HF because they decrease contractility (negative inotropes)

Question 80

What class of agents may cause peripheral VD by inhibiting VSM contraction to some extent?

Answer 80

Class IV Agents (CCBs)

Question 81

What effect might peripheral vasodilation have reflexively on the SA node?

Answer 81

Reflex tachycardia when SA node has reflex activation (negates drug action)

Question 82

What are non-DHP CCBs effective at doing?

Answer 82

significantly affect nodal tissues. | they may also be effective in calcium-dependent EADs in damaged myocardial tissues.

Question 83

ADRs of non-DHP CCBs?

Answer 83

* Constipation (verapamil) * Peripheral edema (more so with DHP’s/diltiazem)
 * Gingival hyperplasia → swollen gums (verapamil/diltiazem) * Flushing/headache/hypotension (diltiazem)

Question 84

What are 3 agents that treat arrhythmias that are "non-classified" agents?

Answer 84

1. Adenosine 2. Digoxin 3. Magnesium

Question 85

What drug can induce complete, but transient AV nodal block?

Answer 85

Adenosine

Question 86

What is the ADR of Adenosine?

Answer 86

“ sense of impending DOOM”

Question 87

How is Adenosine administered?

Answer 87

IV push only

Question 88

What is the half-life of adenosine?

Answer 88

10 seconds

Question 89

How fast must the IV push be given for adenosine?

Answer 89

within 3 seconds

Question 90

What are 2 drugs that can decreases the effect of adenosine?

Answer 90

theophylline, caffeine

Question 91

``` What drug: • inhibits Na/K ATPase membrane pump • increases intracellular calcium • shortens the action potential duration • increases vagal activity? ```

Answer 91

Digoxin

Question 92

What is the main pharmacological property of Digoxin in treating arrhythmias?

Answer 92

its ability to decrease AV nodal conduction (Vagal-like effect) → mimics PNS

Question 93

digoxin will affect the conduction system similarly to what is seen when the PNS is activated; these tissues are primarily the ___________.

Answer 93

SA and AV nodes

Question 94

Why is Digoxin favored over Class II and Class IV agents in treating patients with supraventricular arrhythmias who also have heart failure?

Answer 94

Digoxin slows SA and AV nodes and treats HF as well because it has neg. inotropic effect.

Question 95

Study magnesium in notes

Answer 95

. . .