Pharm: Antiarrythmics

Question 1

what causes arrhythmias?

Answer 1

1. abnormal impulse generation: early afterdepolarization, delayed afterdepolarization, disturbances in impulse formation
2. abnormal conduction: can result from depressed conduction (blocks) or reentry mechanisms

Question 2

what is reqd for a reenry mechanism

Answer 2

obstacle that establishes circuit

unidirectional block

conduction time must be long enough that retrograde impulse does not encounter refractor times

Question 3

refractoriness

Answer 3

shorten refractoriness and facilitate conduction: results in removal of the unidirectional block allowing signal to continue normally

prolong refractoriness/depress conduction: causes a bidirectional block such that the loop can no longer continue due to tissue still being refractory and being unable to respond

Question 4

Type 1A

Answer 4

procainamide*

Na+ channel blocker
Dissociates with intermediate kinetics

↓conduction velocity
↑refractoriness
↓autonomic properties

Question 5

Type 1B

Answer 5

lidocaine

Na+ channel blocker
Dissociates with rapid kinetics

No effect on velocity
May ↓refractoriness

Question 6

Type 1C

Answer 6

Flecainide

Na+ channel blocker
Dissociates with slow kinetics

↓conduction velocity
No effect on refractoriness

Question 7

Type III

Answer 7

amiodarone and sotalol

K+ channel blocker

↑refractoriness
↑action potential duration

Question 8

Type II

Answer 8

Beta-blockers, esmolol, metoprolol, propanolol

↓conduction velocity
↑refractoriness
↓autonomic properties

Question 9

Type IV

Answer 9

diltiazem/verapamil
non-DHP CCB’s

↓conduction velocity
↑refractoriness
↓autonomic properties

Question 10

Procainamide

Answer 10

** prototype ** Class 1A NA+ Channel Blocker

MOA: Slows upstroke of action potential (Phase 0), slows conduction, prolongs QRS, prolongs action potential duration

Use: rarely used, but used for atrial and ventricular arr.

SE: excessive potential prolongation, reversible lupus, nausea, diarrhea, hypotension

Question 11

Quinidine

Answer 11

Class 1A NA+ Channel Blocker

MOA: Slows upstroke of action potential (Phase 0), slows conduction, prolongs QRS, prolongs action potential duration

rarely used

toxicity GI [diarrhea, nausea, vomiting (33-50%)], cinchonism (headache, dizziness, tinnitus)

Question 12

Disopyramide

Answer 12

Class 1A NA+ Channel Blocker

MOA: Slows upstroke of action potential (Phase 0), slows conduction, prolongs QRS, prolongs action potential duration

Antimuscarinic effects, precipitates heart failure, urinary retention, dry mouth, blurred vision, constipation

Question 13

Lidocaine

Answer 13

Class 1B Na+ Channel Blocker

* cannot use to tx atrial arrhythmias*

MOA: Shortens Phase 3 repolarization, and decreases duration of AP in ventricular mm. fibers

given IV

Toxicity: Least cardiotoxic of Na+ channel blockers! Hypotension, neurologic (paresthesias, tremor, nausea, lightheadedness)

Note: highly effective in tx. of arrythmias assoc. w/ acute MI

Question 14

Tocainide

Answer 14

Class 1B

Question 15

Mexiletine

Answer 15

Class 1B

Varr.

Question 16

Flecainide

Answer 16

Class 1C Na+ channel blocker

• high incidence of drug induced arrythmias
• cannot be used in structural heart disease

MOA: slows Phase 0 depolarization in ventricular mm. fibers more than class 1A: Blocks both Na+ and K+ channels but does not prolong action potential or QT interval, depresses rate of rise of membrane action potential,

Use: supraventricular arrythmias

Question 17

Moricizine

Answer 17

Class 1C Na+ channel blocker

Question 18

Propafenone

Answer 18

Class 1C Na+ channel blocker

Question 19

-olol

Answer 19

Beta blockers: propanolol, esmolol (short acting), metoprolol (B1 selective)

MOA: inhibit phase 4 depolarization in SA and AV nodes thus prolonging conduction, decreasing HR and contractility, and decreasing myocardial O2 demand

uses: Tachyarrhythmias, AF, AFib, AV nodal re-entrant tachycardia, hypertension, heart failure, ischemic heart disease
toxicity: Bradycardia, heart block, potential worsening reactive airway disease (as nonselective)

Question 20

Amidiorone

Answer 20

Class III K+ Channel Blocker

Diminish outward K+ during repolarization, increased duration of AP, prolong effective refractory period

Use: AFib, recurrent VT, adjunct to ICD to reduce uncomfortable discharges

Toxicity: accumulates in tissues, heart, lung, liver, skin, tears, can cause skin deposits and gray-blue skin color and thyroid problems

MANY DRUG INTERACTIONS!

Question 21

Dofetilide

Answer 21

Class III K+ Channel Blocker

Therapeutic Use:
Life-threatening ventricular arrhythmias, maintenance of sinus rhythm in AFib

can cause dose related TdP

Question 22

Sotalol

Answer 22

Class III K+ Channel Blocker

has QT prolonging effects thus must be initiated in the hospital

Question 23

Verapamil

Answer 23

Class IV Ca2+ channel blockers (non-DHP)

do not use in patients with VT –> will cause Vfib

MOA: decrease inward Ca2+ current, decrease rate of phase 4 depolarization, slows conduction in AV node (Ca2+ dependent tissues)

Use: SVT, decrease ventricular rate in AFib and AF, angina, HTN

Toxicity: ***Hypotension and ventricular fibrillation if given to a patient with VT misdiagnosed as SVT

Question 24

Diltiazem

Answer 24

Class IV Ca2+ channel blockers (non-DHP)

MOA: decrease inward Ca2+ current, decrease rate of phase 4 depolarization, slows conduction in AV node (Ca2+ dependent tissues)

Use: SVT, angina, hypertension

toxicity: Edema, headache, AV block, bradycardia, hypotension

Question 25

Adenosine

Answer 25

Nucleoside which activates inward rectifier K+ current and inhibits Ca2+ current resulting in marked hyperpolarization and increased refractory period Use: DOC for conversion of paroxysmal SVT t1/2 <10 seconds- given in IV flush toxicity: Flushing, shortness of breath, chest burning, high grade AV block, atrial fibrillation, headache, hypotension, nausea, paresthesias- all of these are short lived

Question 26

atropine

Answer 26

MOA: Blocks actions of acetylcholine at parasympathetic sites, increases cardiac output use: Bradycardia, neuromuscular blockade reversal, cholinergic poisoning toxicity: Arrhythmia, tachycardia, dizziness, constipation, urinary retention

Question 27

Digoxin

Answer 27

Inhibits Na+/K+ ATPase, results in positive inotropy, increased intracellular Na+, decreased Ca2+ expulsion, increased free Ca2+. Decreased HR, decreased refractory period, decreased conduction velocity Use: AFib, SVT, heart failure Toxicity: Nausea, vomiting, diarrhea, disorientation, visual disturbances, aberration of color perception, delayed afterdepolarization

Question 28

↑ repolarization time, QTc interval, and risk of TdP

Answer 28

Class 1a and III

Question 29

↓ HR (may cause bradycardia), force of contraction (may ↓ stroke volume), and ↑ PR interval (may cause 2nd or 3rd degree heart block)

Answer 29

Class II and IV

Question 30

work only on ventricular tissue (cannot be used in AFib or AF)

Answer 30

Class 1b

Question 31

should never be used after an MI or with CHF or severe LV hypertrophy (structural heart disease)

Answer 31

Class 1C

Question 32

supraventricular arrhthmias

Answer 32

originate above the Bundle of His and characterized by normal QRS complexes ```  Sinus bradycardia  Sinus tachycardia  Paroxysmal supraventricular tachycardia  Atrial flutter  Atrial fibrillation  Wolff-Parkinson-White  Premature atrial contractions ```

Question 33

ventricular arr.

Answer 33

``` all originate below the Bundle of His  Premature ventricular contractions  Ventricular tachycardia  Ventricular fibrillation ```

Question 34

acute tx of atrial fibrillation?

Answer 34

Depolarization from ectopic focus or re-entrant circuit impact atria. No single pacemaker in control. “Irregularly irregular” 1, B-blockers (propranolol, metoprolol, esmolol) 1st choice in high catecholamine states. Should not be used acutely in systolic heart failure. 2. Non-DHP CCB’s (verapamil, diltiazem) IV produce rapid effects 4-5 minutes. 3. Digoxin has much slower onset (max effect 6-8 hours), less effective than BB/CCB in increased sympathetic tone

Question 35

chronic tx of A fib?

Answer 35

oral BB, CCB - not digoxin long term strategy is rate control > rythym control

Question 36

PAROXYSMAL SUPRAVENTRICULAR | TACHYCARDIA (PSVT) tx

Answer 36

AV nodal re-entry Acute treatment: IV adenosine (DOC), verapamil, or diltiazem Chronic: radiofrequency catheter ablation potentially curative

Question 37

premature ventricular contractions (PVCs) tx

Answer 37

Ventricular arrhythmias arise from irritable foci within ventricular myocardium blockers within first 24 hours after MI if no contraindications (improves survival)

Question 38

sustained V tach tx

Answer 38

Hemodynamic instability: synchronous cardioversion Stable VT patients: procainamide, sotalol, amiodarone Implantable cardioverter/defibrillator for:

Question 39

torsades de pointes tx

Answer 39

Hemodynamic compromise: electrical cardioversion Hemodynamically stable: Mg