Antiarrhythmic drugs DR. J. DAWSON - PowerPoint Presentation

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Antiarrhythmic drugs

DR. J. DAWSON

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P axis normal (P waves positive in I and aVF)

Rate <60 bpm; marked sinus bradycardia (<50 bpm)

May be seen in normal adults, particularly athletes, and

in elderly individuals Increased

vagal tone or vagal stimulation; drugs (e.g

. -

blockers,

calcium

channel blockers); ischemia

/ infarction

Atropine; pacing for sick sinus syndrome

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Supraventricular Tachyarrhythmiaspresentation can include: palpitations, dizziness,

dyspnea

, chest discomfort,

presyncope

/syncope

may precipitate CHF, hypotension, or ischemia in patients with underlying cardiovascular disease

untreated

tachycardias

of long duration (days) can cause tachycardia induced

cardiomyopathy

arrhythmias involving the AV

node

may terminate spontaneously,

after vagal stimulation

, or adenosine treatment

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tachyarrhythmias that originate in the atria or AV junction

this term is used when a more

specic

diagnosis of mechanism and site of origin cannot be made

characterized

by narrow QRS unless there is pre-existing bundle branch block or aberrant ventricular

conduction (abnormal conduction due to a change in cycle length)

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Sinus Tachycardia

sinus rhythm with rate >100 bpm

occurs

in normal subjects with increased sympathetic tone (e.g. exercise, anxiety, pain, pregnancy

), alcohol

use,

caeinated

beverages, drugs (e.g. -adrenergic agonists, anticholinergic drugs)

systemic

etiology

: fever, hypotension, hypovolemia,

anemia

, thyrotoxicosis, CHF, MI, shock,

pulmonaryembolism

treatment: treat underlying disease; consider -blocker if symptomatic, calcium channel blocker

if -

blockers contraindicated;

ivabradine

may be considered as an alternative agent for inappropriate

sinus tachycardia

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Atrial Flutterrapid, regular atrial depolarization from a macro re-entry circuit within the atrium (most

commonly right

atrium)

• atrial rate 250-350 bpm, usually 300

bpm

AV block usually occurs; it may be

xed

(e.g. 2:1, 3:1, 4:1, etc.) or variable

•

etiology

: hypertension, cardiomyopathy , in association with atrial

brillation

; less

oen

, CAD

, thyrotoxicosis

, mitral valve disease, cardiac surgery, COPD, PE, pericarditis

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ECG: sawtooth

utter waves (most common type of utter, called “isthmus dependent, typical utter)

in inferior

leads (II, III,

aVF

); narrow QRS (unless aberrancy); commonly seen as 2:1 block with HR of

150

in

atrial utter with 2:1 block, carotid sinus massage (

rst

check for bruits), Valsalva

maneuver

,

or adenosine

may decrease AV conduction and allow utter waves to be more easily seen

• treatment of acute atrial utter

if unstable (e.g. hypotension, CHF, angina): electrical cardioversion

if stable:

1. rate control: -blocker, diltiazem, verapamil, or digoxin

2. chemical cardioversion:

sotalol

, amiodarone, type I

antiarrhythmics

, or electrical cardioversion

anticoagulation

guidelines same as for patients with

AFib

treatment of long-term

AFib

includes

antiarrhythmics

and radiofrequency (RF) ablation (success

rate dependent

on site of origin of atrial utter)

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Atrial Fibrillation

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most commonly sustained arrhythmia• incidence increases with age (10% of population >80

yr

)

• symptoms: palpitations, fatigue,

dyspnea

, syncope, may precipitate or worsen heart

failure

may be associated with thromboembolic events (stroke risk can be assessed by CHADS2 score in

nonvalvular

AFib

; CHADS2-VASc if the former gives a score of 0 or 1)

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no

organized P waves due to rapid atrial activity (350-600 bpm) causing a chaotic

brillatory

baseline

irregularly irregular ventricular response (typically 100-180 bpm), narrow QRS (unless aberrancy

or previous

BBB)

wide QRS complexes due to aberrancy may occur following a long-short cycle sequence (“

Ashman phenomenon

”)

loss of atrial contraction, thus no “a” wave seen in JVP, no S4 on auscultation

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Rate control: -blockers, diltiazem, verapamil

A

nticoagulation: use either warfarin or novel oral

anticoagulant

C

ardioversion (electrical)

– if

AFib

<48 h, can usually

cardiovert

without anticoagulation

– if

AFib

>48 h,

anticoagulate

for 3

wk

prior and 4

wk

aer

cardioversion due to risk

of unstable

intra-atrial

thrombus

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Wolff-Parkinson-White Syndrome (WPW)congenital defect present in 1.5-2/1000 of the general population

• an accessory conduction tract (Bundle of Kent; can be in right or le atrium) abnormally allows early

electrical activation of part of one ventricle

• impulses travel at a greater conduction velocity across the Bundle of Kent thereby

eectively

‘bypassing

’ AV node

since the ventricles are activated earlier, the ECG shows early ventricular depolarization in the form

of initial

slurring of the QRS complex – the so-called “delta wave”

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atrial impulses that conduct to the ventricles through both the Bundle of Kent and the normal

AV node/His-Purkinje

system generate a broad “fusion complex”

• ECG features of WPW

PR interval <120

msec

delta wave: slurred upstroke of the QRS (the leads with the delta wave vary with site of bypass)

widening of the QRS complex due to premature activation

secondary ST segment and T wave changes

tachyarrhythmias

may occur – most

oen

AVRT and

AFib

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Ventricular Tachyarrhythmias

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treatment sustained VT (>30 s) is an emergency requiring immediate treatment

hemodynamic compromise: electrical cardioversion

no hemodynamic compromise: electrical cardioversion, amiodarone, type

Ia

agents (procainamide

, quinidine

)

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treatment: IV magnesium, temporary pacing, isoproterenol and correcting the underlying cause of

prolonged QT, electrical cardioversion if hemodynamic compromise

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Class 1Na

+

channel blockers decrease likelihood of re-entry & thereby prevent arrhythmia by:

1) decreasing conduction velocity

2) increasing refractory period of ventricular myocytes

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Class 1

↓ automaticity in SA nodal cells by

Shifting threshold to more positive potentials

↓ slope of phase 4 depolarization

Block of Na

+

channels leaves fewer channels available to open in response to membrane depolarization thereby

raising

threshold for AP firing and slowing rate of depolarization

→

extend duration of phase 4 and ↓ heart rate

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Class 1

Act on ventricular myocytes to ↓re-entry – achieved by ↓ upstroke velocity of phase 0 & for some Na+ channel blockers, by prolonging repolarization

By ↓ phase 0 upstroke velocity, Na+ channel blockers ↓conduction velocity through cardiac tissue

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Class 1B-

mild

Na

+

block (↓ phase 0 upstroke rate; shortened AP duration)

Class

1A-

moderate

Na

+

block ( ↓↓ phase 0 upstroke rate; prolonged AP duration)

Class

1C-

marked

Na

+

block (↓↓↓ phase 0 upstroke rate; no change in AP duration)

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Class 1ADisopyramide

Procainamide

Quinidine

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Class 1A

Procainamide

Used

i.v.

for acute suppression of supraventricular

&

ventricular

arrhythmias

Used

p.o.

for long-term suppression of supraventricular & ventricular arrhythmia

C

an

suppress SA & AV nodal activity, especially in patients w nodal disease & can cause heart

block by 1. prolonged

use

association with

↑

risk of ventricular

tachycardia and 2. has

some ganglionic blocking activity →hypotension &

↓

myocardial contractility

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Class 1AAcetylated in liver

and

excreted by kidney

In

renal failure or

patients

who are rapid

acetylators

, high serum levels of

metabolite

may accumulate

Effects - hypotension

,

diarrhoea,

pleuritis

,

pericarditis, asystole, hallucination,

psychosis,

torsades

de

pointes,

fever,

rash, development

of lupus-like syndrome -characterized by rash, arthralgia, connective tissue inflammation after 6 months of

therapy

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Class 1BLidocaine

Mexiletine

-

orally

active form of

lidocaine

Phenytoin -

used

to reverse digoxin induced atrial & ventricular

arrhythmias

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Class 1B

Lidocaine

Acute

management of ventricular

arrhythmias

especially in patients with myocardial

infarction and Local anaesthetic

Purkinje cells:

depresses

phase 0

depolarization

↓

conduction

velocity

decreases slope of normal phase 4 depolarization of pacemaker cells & raises the threshold

→

↓pacemaker

activity

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Administered i.v.

only, rapid distribution & hepatic metabolism

T ½ depends greatly on hepatic blood flow; reduced flow (heart failure / elderly ) or liver disease

→

greatly

↑

serum lidocaine concentrations

→

toxic effects

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Class 1CFlecainide

Propafenone

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For supraventricular arrhythmias in patients without myocardial structural abnormalities

Marked

Na+ channel

blockade

By markedly

↓ rate of phase 0 upstroke of ventricular cells, suppresses premature ventricular

contractions

Effects -

Proarrhythmogenic

effects – The Cardiac Arrhythmia Suppressor Trial (CAST) study showed

↑

in mortality rate in patients taking flecainide

dizziness

, tremor, light-headedness, flushing, blurred vision, metallic

taste

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Class 2

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Class 3Amiodarone

Sotalol

Ibutilide

Dofetilide

Bretylium

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Amiodarone

broad spectrum of antiarrhythmic action –properties of all classes, but predominantly class 3 action

Block I

K

channels → lengthening time to repolarize ; prolong phase 3 of AP

Class 1

Class 2

Class 4

Also is vasodilator ( 2

o

ɑ - blockade &

Ca

2+

channel blockade)

Negative inotropic agent (2

o

β

- blockade

&

Ca

2+

channel blockade)

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AmiodaroneBoth form

p.o.

/

i.v

Structurally

related to thyroid hormone

Used

for treating supraventricular arrhythmias; ventricular

tachyarrhythmia

A.E. - Interstitial

pulmonary

fibrosis, Tremor

,

ataxia, Hepatocellular necrosis, Photosensitivity, Corneal

microdeposits

, Thyroid

dysfunction (hypo- or hyper

), Blue

skin

discolouration

2

0

iodine accumulation

Recommendations

- LFTs

, TFTs, lung function

tests, prior

to initiating & during treatment

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AmiodaroneSubstrate for liver cytochrome CYP3A4; drug levels increased by drugs that inhibit this enzyme e.g. erythromycin, clarithromycin, diltiazem, simvastatin; grapefruit juice

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Class 4

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