Pharmacology for Anaesthesia and Intensive Care

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14 Anti-arrhythmics

Table 14.1.Vaughan–Williams classification.

Class Mechanism Drugs

aNa+channel blockade – prolongs the

refractory period of cardiac muscle

quinidine, procainamide,

disopyramide

Ib Na+channel blockade – shortens the

refractory period of cardiac muscle

lidocaine, mexiletine, phenytoin

Ic Na+channel blockade – no effect on the

refractory period of cardiac muscle

flecainide, propafenone

II β-Adrenoceptor blockade propranolol, atenolol, esmolol

III K+channel blockade amiodarone, bretylium, sotalol

IV Ca^2 +channel blockade verapamil, diltiazem

Uses

Digoxin is widely used in the treatment of atrial fibrillation and atrial flutter. It has

been used in heart failure but the initial effects on cardiac output may not be sus-

tained and other agents may produce a better outcome. It has only minimal activity

on the normal heart. It should be avoided in patients with ventricular extrasystoles

or ventricular tachycardia (VT) as it may precipitate ventricular fibrillation (VF) due

to increased cardiac excitability.

Treatment starts with the administration of a loading dose of between 1.0 and

1.5 mg in divided doses over 24 hours followed by a maintenance dose of 125–

500 μgper day. The therapeutic range is 1–2μg.l−^1.

Mechanism of action

Digoxin has direct and indirect actions on the heart.


Direct – it binds to and inhibits cardiac Na+/K+ATPase leading to increased

intracellular Na+and decreased intracellular K+concentrations. The raised intra-

cellular Na+concentration leads to an increased exchange with extracellular

Ca^2 +resulting in increased availability of intracellular Ca^2 +,which has a positive

inotropic effect, increasing excitability and force of contraction. The refractory

period of the AV node and the bundle of His is increased and the conductivity

reduced.


Indirect – the release of acetylcholine at cardiac muscarinic receptors is enhanced.

This slows conduction and further prolongs the refractory period in the AV node

and the bundle of His.

Inatrial fibrillation the atrial rate is too high to allow a 1:1 ventricular response. By

slowing conduction through the AV node, the rate of ventricular response is reduced.

This allows for a longer period of coronary blood flow and a greater degree of ven-

tricular filling so that cardiac output is increased.