Antiarrhytmic drugs

By:Dr.Zharif

Vaughan Williams classification of Antiarrhythmic agents(International Classification):

I(Membrane Stabilizing agents)

Ia((Na+) channel block (intermediate association/dissociation)

Mech of action

block the fast sodium channel(depresses the phase 0 depolarization (reduces Vmax))By:

1.prolongs the action potential duration by slowing conduction.

2.decreased conductivity

3.increased effective refractory period

Indications:

supraventricular tachycardia, ventricular tachycardia, symptomatic ventricular premature beats, and prevention of ventricular fibrillation.

Procainamide treatment of atrial fibrillation in the setting of Wolff-Parkinson-White syndrome, and in the treatment of wide complex hemodynamically stable tachycardias. While procainamide and quinidine may be used in the conversion of atrial fibrillation to normal sinus rhythm, they should only be used in conjunction with an AV node blocking agent (ie: digoxin, verapamil, or a beta blocker), because procainamide and quinidine can increase the conduction through the AV node and may cause 1:1 conduction of atrial fibrillation, causing an increase in the ventricular rate.

Drugs 1a

Quinidine-

200-600mg every 4-6 hour peroral during attack

Procainamide-

250-750mg every 4-6 hour peroral or

10-15mg/kg I/V droplet with 25mg/min after that 1-6 mg/min

Disopyramide –

100-200 mg every 6-8 hours peroral

Ib((Na+) channel block (fast association/dissociation))

Mech.of action

fast onset and offset kinetics, meaning that they have little or no effect at slower heart rates, and more effects at faster heart rates

shorten the action potential duration and reduce refractoriness

tend to be much more specific for voltage gated Na channels than Ia

more activity with increasing heart rates

Indication

ventricular tachycardia and symptomatic premature ventricular beats, and prevention of ventricular fibrillation.

Drugs 1b

Lidocaine

1-3mg/kg i/v droplet 25-50mg/min till 1-4mg/min

Mexiletine-

200-400mg every 8 hours peroral

Ic((Na+) channel block (slow association/dissociation))

Mech.of action

decrease conductivity but have a minimal effect on the action potential duration. Of the sodium channel blocking antiarrhythmic agents

Indication :

life-threatening ventricular tachycardia or ventricular fibrillation, and for the treatment of refractory supraventricular tachycardia

Imaline(AJMALINE)-I/V 50mg till 75 mg 7-10 min

Gilurytmal(in russian)

Drugs 1c

Propafenone-

150-300mg every 8 hour i/v

Moricizine-

150-300 mg every 8-12 hour i/v

II(Beta blocker)

Mech of action

Beta blockers block the action of endogenous catecholamines (epinephrine (adrenaline) and norepinephrine (noradrenaline) in particular), on β-adrenergic receptors, part of the sympathetic nervous system which mediates the fight or flight response.

Drugs II

Propranolol

10-100 mg every 6 hour peroral

III(K+ channel blocker)

Mech of action

block the potassium channels, thereby prolonging repolarization. The prolongation of the action potential duration and refractory period, combined with the maintenance of normal conduction velocity, prevent re-entrant arrhythmias.

Side effect:

These agents include a risk of torsades de pointes

Drugs III

Amiodarone

600-1600mg/day 1-3 week

next 3rd week 200-400 mg/day

Sotalol (is also a beta blocker)

80-320 mg every 12 hours peroral

IV(Ca2+ channel block)

Mech of action

blocking voltage-gated calcium channels (VGCCs) in muscle cells of the heart and blood vessels

decrease in cardiac contractility

less contraction of the vascular smooth muscle of vessel-vasodilation

decreases total peripheral resistance,

decreases cardiac output.

low blood pressure

Drugs IV

verapamil

80-320 mg every 6-8 hours peroral

5-10 mg for 1-2 min i/v

V(Work by other or unknown mechanisms)

digoxin

1,25-1,5 mg fractional peroral in 24 hours

next 0.125-0,375 mg/day i/v

adenosine

6mg rapidly i/v

if no effect inbetween 1-2 minutes

12 mg rapidly i/v

Mnemonics

"some block potassium channels"

Class I "Some" = S = Sodium blocker

Class II "Block" = B =Beta blockers

Class III "Potassium"=P= Potassium channel blockers

Class IV "Channels" = C =Calcium channel blockers

Class I agents

Class IA “Double Quarter Pounder” (Disopyramide, Quinidine, Procainamide),

Class IB “Lettuce, Tomato, Mayo” (Lidocaine, Tocainide, Mexilitine)

Class IC “More Fries Please” (Moricizine, Flecainide, Propafenone)

Class III agents:

"A Big Dog Is Scary" (Amiodarone, Bretylium, Dofetilide, Ibutilide, Sotalol)

Class IV agents:

"Very Nice Drugs" (verapamil, nifedipine, diltiazem)

Russian classification for Antiarrhytmic drugs

Supraventricular arrhythmia

Drugs	During attack	Prophylactic	Start action	Prolong action
Izoptine	i/v 10mg(seldom 15-30 mg )with 1mg/min PerOS 40-120 mg till 160 mg	PerOS 40-120mg 4-6 times /day	i/v- 1st min. perOS-during 1 hours	4-8 hours
Quinidine	PerOS 0.2-0.6 g	PerOS 0.2-0.4g 4-6 times/day	30 min.	4-6 hours
Novocainamide	i/v 0.5-1 g or i/v every 2 min 0.1-0.2g or i/m o.5-1g or PerOS 1-1.5g	i/v 2-3mg/min or PerOS o.5g 4-6 times/day	i/v-1st minute perOS-30 min.	3-4 hours
Imaline	i/v 50 mg till 75 mg in duration 7-10 min or PerOS 0.05-0.1 g	perOs 0.05-1g 3-4 times/day	i/v-1st min.	6-8 hours
Ritmodan	i/v 2 mg/kg do 150 mg in duration 5 min. or perOS 0.2-0.3g	perOS 0.1-0.2g 3-4 times/day	i/v-1st min. perOS-30 min.	i/v-10 min perOS-4-6 hours
etmozine	i/v 2-2.5 mg/kg in duration 5-10 min	PerOS 0.2g 3-4 times/day	i/v-1st min perOS-24-48hours	i/v 20-25min perOS 6-8 hours
Obzidane	i/v 10mg in duration 7-10 min or PerOS 20-160mg	PerOS 20-80mg 4times/day	i/v- 1st min perOS-30 min.	i/v 2-4 hours perOS 3-6 hours
Kordaron	i/v 5mg/kg in duration 5 min	perOS: 1st week 200-400mg 3 times/day 2nd week 1-2 tab. 2 times/day 3rd week 1-2 tab./day 2 day rest in 1 week	i/v-1st min	i/v-20-30 min perOS- week

Ventricular arrhytmia

Drugs	During attack	Prophylactic	Start action	Prolong action
Lidocaine And trimecaine	i/v 80-100mg in duration 3-5 min seldom 150-200mg in duration 10-20 min.	i/v rapidly 80-100mg next droplet 2-3mg/min i/m 400-600mg in 3 hours	i/v-1st min. i/m- 10-15 min.	i/v-10-15min i/m 3hours
Mexitiline	i/v 75-250mg in duration 5-15 min or PerOS 0.3-0.4g	i/v rapidly 75-250mg next droplet or perOS 0.2-0.4g 3 times/day	i/v-1st min. perOS-30min.	i/v-3-8hours perOS- 6-8 hours
Diphenine		perOS:slow 0.1g 3-4 times fast 0.2g 5 times/day	3-5th day	Stop during 6-12 after stop taken

Ref:

1. Internal medicineRussian text book
2. Hospital therapyRussian text book
3. Cycle Russian therapy
4. American heart website
5. wikipedia