8. gopal antiarrhythmic pcol350_8502010

8/13/2019 8. Gopal Antiarrhythmic PCOL350_8502010

1/18

PCOL350.6 /850.6Antiarrhythmics

Venkat Gopal

Tel: 374-9110; 373-3923

[email protected]

2010 1.1


2/18

List of Antiarrhythmic Drugs1. Class I: Na+ Channel Blockers:

Quinidine, Lidocaine, Flecainide, Encainide

Block Conduction - Affects Phase 0 of AP.

2. Class II: Non-selective - Blockers:

(Metoprolol, Sotalol)SA Node Automaticity

Conduction Velocity in AV Node.

3. Class III: Amiodarone,Bretylium, SotalolProlongs Action Pot. Duration & QT Interval,

4. Cass IV: CCBs: (Verapamil, Diltiazem)

Slows Conduction Velocity in AV NodeSVT


3/18

Objectives

Following this event, the learner will be able to: Describe action potentials and the ion currents in various

phases

List the 4 (or 5) classes of antiarrhythmic action. Give 1-

2 examples of drugs with each effect. Describe 2 mechanisms of tachyarrhythmia

Identify torsades de pointes

Describe the main outcome of the CAST trial

Describe an approach to the treatment of AVRNT, AFib,VT.

2010 1.1


4/18

Clinical background

Definition: any heart rhythm other than normal sinus

Bradycardia: < 60 bpm

Tachycardia: >100 bpm< 30: pacemaker (atropine while waiting)

> 150 + unstable: DC cardioversion

2010 1.1


5/18

Basic Science Review

2010 1.1

Na

K

Ca

NaK

Ca


6/18

Review EP: Phase 0 Conduction Velocity Phase 1,2, 3: QT Interval


7/18

Complexity: the Na channel

2010 1.1

The h gate is voltage dependent (closes at +ve voltage)

Calcium and potassium channels are also voltage

dependent


8/18

More (but quick) review

2010 1.1

Sinus + AV nodes different:

Spont. depol (pacemaker)

Slow phase O (cond. veloc)


9/18

Vaughan-Williams (1970)

Class 1a Na channel(K channel)

cond. velocQT (refr)

quinidinedisopyramide

Class 1b Na channel

(inactive only)

cond. veloc*

QT

lidocaine

mexiletine

phenytoin

Class 1c Na channel cond. veloc

, QT

flecainide

propafenone

Class 2 Ca channel

(indirect thru BB)

cond. veloc

Sinus, AV node

metoprolol

Class 3 K channel QT sotalol*,

amiodarone

Class 4 Ca channel(direct)

cond. velocSinus, AV node

Verapamil

diltiazem

Class 5 ? Purine ag. AV node adenosine2010 1.1


10/18

Types of arrhythmias

Generation Pacemaker cells

Too fast, (too slow)

2010 1.1

Condn (re-entry) Within or between

chambers

Class 2, 4

pacemakerClass 1,2,3,4,

SVT, Afib, AFlttr., VFlttr, VFib


11/18

The proarrhythmic effect(CAST trial, New Engl J Med 1991; 324: 781-8)

Encainide (n= 432), flecainide (323), placebo (743)

Drug Placebo

deaths 63 26(p


12/18

A word on amiodarone

2010 1.1

synthesized 1961

angina, later arrhythmias

approved in Canada 1980, USA 1985


13/18

More words on amiodarone

Class 3, 2, 4 activity-no better antiarrhythmic

Good for AFib, Aflutter, VT, VF

Little proarrhythmic effect Weird PK: Vd=66L/kg; t = 25-100 d.

i.v and oral loading doses (10 gr,1-3 weeks)

Lots of AE (75% after 2 years; doserelated (Thyroid, lung, liver, eye, skin, etc!)

2010 1.1


14/18

Amiodarone AEGoldschager N et al.Arch Int Med 2000; 160: 1741

Low Dose(


15/18

Nutshel ls Class I antiarrhythmic drugs act primarily as sodium

channel blockers and they have greater access or higheraffinity for cells in the activated or inactivated state than

for cells in the resting state.

Cells in an ischemic area spend a larger proportion of

time in the activated and inactivated states than in the

resting state. It follows that the sodium channel blockers

will exert a greater effect in ischemic tissue than in

normal tissue.

By further depressing conduction in the areas with

depressed conduction (e.g. ischemic area), sodium

channel blockers often produce bidirectional block. By

this means they abort re-entry mechanisms to

overcome arrhythmias.


16/18

Nutshel lsBeta- blockers are most effective in conditions associated with

high sympathetic activity.

Calcium channel blockers are the drugs of choice in

supraventricular tachycardias. Note that Verapamiland

diltiazem have a proportionally greater effect on cardiac tissuethan vascular tissue compared to nifedipine, and they are the

drugs of choice. Nifedipine is not recommended because of the

reflex tachycardia associated with this agent.


17/18

Summary

There are 4 (5?) classes of antiarrhythmic effect.

Drugs may act by more than 1 mech. (sotalol=2+3)

Proarrhythmic effects are common, esp. TdP

TdP caused by prolonged QT (repolarizationphase)

Amiodarone(acts - 2,3, 4 Class) is the nuclear

weapon despite adverse effects on prolonged use.

2010 1.1


18/18

8. gopal antiarrhythmic pcol350_8502010

Documents