class antiarrhythmic drugs

1

ANTIARRHYTHMICS

Dr. RAGHU PRASADA M SMBBS,MDASSISTANT PROFESSOR DEPT. OF PHARMACOLOGYSSIMS & RC.

Normal Sinus Rhythm

Heart rhythm is determined by SA node = Cardiac Pacemaker

Sinus rhythm Specialised pacemaker

cells spontaneously generate APs

APs spread through the conducting pathways

Normal sinus rate 60-100 beats/min

Cardiac Action Potential

Divided into five phases (0,1,2,3,4)• Phase 0 – rapid depolarization • Phase 1 – early repolarization• Phase 2 – plateau phase• Phase 3 – rapid repolarization • Phase 4 – resting phase, diastolic depolarization

0 1 2 3 4

• Effective refractory period• absolute refractory period• relative refractory period

1

0

2

3

4

ARP RRP

Cardiac Action Potential

What is an Arrhythmia ?

Irregular rhythm

Abnormal Rate

Conduction abnormality

What causes an arrhythmia?

Changes in automaticity of the PM Ectopic foci causing abnormal APs Reentry tachycardias Block of conduction pathways Abnormal conduction pathways (WPW) Electrolyte disturbances and DRUGS Hypoxic/Ischaemic tissue can undergo spontaneous

depolarisation and become an ectopic pacemaker

ECG showing

wave segments

Contraction of atria

Contraction of ventricles

Repolarization of ventricles

Vaughan-Williams Classification

Class Mechanism Example

I Na channel blockersMembrane Stabilisers

Lignocaine

II Beta Blockers Metoprolol

III K channel blockers Amiodarone

IV Ca channel blockers Verapamil

Other Digoxin. Adenosine.MgSO4. Atropine

Class I

IA IB IC

They ↓ automaticity in non-nodal tissues (atria, ventricles, and purkinje

fibers)

They act on open Na+ channels or

inactivated only

“use dependence”

Have moderate K+ channel blockade

IA – Quinidine, Procainamide, Disopyramide Slowing the rate of rise in phase 0 They prolong action potential & ERP ↓ the slope of Phase 4 spontaneous depolarization ↑ QRS & QT interval Slow rate of dissociation with open Na+ channels

Vmax

APD

Antimalarial, antipyretic, skeletal muscle relaxant & atropine like action.

A/E ▪ quinidine syncope from

ventricular tachycardia▪ Diarrhoea▪ “Cinchonism” – tinnitus,

vertigo, headache, nausea & blurred vision.

200-400 mg orally tds

C/I

AV block

QT prolongatio

n- Torsades de pointes Digoxin,

enzyme inducer

Myasthenia gravis

IA – QUINIDINE

IB – Lidocaine, Mexiletine, Phenytoin & Tocainide They shorten Phase 3 repolarization ↓ the duration of the cardiac action

potential Prolong phase 4 They show rapid association &

dissociation with inactiated Na+ channels

Vmax

APD

IB – Lidocaine

Used IV because of extensive 1st pass metabolism No vagolytic effects Least cartiotoxic CNS side effects LD – 150-200mg for 15mins MD – 1-4mg/min Used for VT Propranolol ↑ its toxicity

IC – Flecainide, Encainide, Propafenone & moricizine

markedly slow Phase 0 depolarization slow conduction in the myocardial tissue minor effects on the duration of action potential and

ERP reduce automaticity by increasing threshold

potential rather than decreasing slope of Phase 4 depolarization.

Vmax

«APD

Class II drugs – Propranolol, Metoprolol, Esmolol, Acebutolol

Depress phase 4 depolarization

depress automaticity prolong AV conduction

↑ ERPProlong PR interval HR

contractility

Class II drugs

Propranolol Esmolol

Resistant v arrhythmia SVT

10 – 80 mg TDS LD 500mg / kg / min for 1 min

1 – 3 mg in 50ml 5%D – 1 min MD 50mg / kg / min for 4 min

Contraindication

Asthma

Sinus Bradycardia

AV block

Severe CHF

Class III drugs - Amiodarone , Dronedarone, Vernakalant, Ibutilide, Bretylium, Dofetilide

K+ channel blockers AP / ERP without

affecting Phase 0 / 4 Prolong QT & PR APD

Amiodarone

Iodine – containing

Block K+ Na+ , Ca++

& β

HR & AV nodal

conduction

QT prolongatio

n

Uses =VF, VT & AF

Arrhythmic

death in post MI

LD-150mg slow IV

MD-1mg/min for

6hrs

A/E – heart block, pulmonary, hepatitis, dermatitis, corneal

deposits & thyroidism

Interaction – digoxin, diltizem & quinidine

class III

Dronedarone-Without iodine, short t1/2, AF Oral 400mg twice daily

Vernakalant-Na+ & K+, atrial ERP, A/D faster, AF

Azimilide-Block both rapid & slow k+ channel

Tedisamil

Class IV – Verapamil, Diltiazem

Mechanism-block L-type calcium channels.• Rate of phase 4 in SA / AV node• Slow conduction – prolong ERP• Phase 0 upstroke

Verapamil

Stronger action on heart than smooth muscle Used in supraventricular arrhythmia 80-120mg three times a day A/E – ankle oedema, constipation C/I – AV block, LVF, hypotention & WPW It digoxin toxicity

Uses

Sympathetically mediated

arrhythmia

Sinus tachycardia

AES

Supraventricular arrhythmia – AF /

PSVT

Ventricular arrhythmia – QT

VPC WPW

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