A Textbook of Clinical Pharmacology and Therapeutics

should be given to insertion of an implantable cardioverter
defibrillator (ICD), if the patient is considered at high risk of further
episodes and/or serious ventricular dysrhythmias remain
inducible on electrophysiological testing.
Ventricular fibrillation: See above under Advanced life support.
As discussed above for ventricular tachycardia, implantation
of an ICD should be considered.
BRADYDYSRHYTHMIAS
ASYSTOLE
See above under Advanced life support.
Sinus bradycardia
1. Raising the foot of the bed may be successful in increasing
cardiac output and cerebral perfusion.
2. Give atropine (see below).
3. Discontinue digoxin, beta-blockers, verapamil or other
drugs that exacerbate bradycardia.
4. Pacemaker insertion is indicated if bradycardia is
unresponsive to atropine and is causing significant
hypotension.
Sick sinus syndrome (tachycardia–bradycardia
syndrome)
Treatment is difficult. Drugs that are useful for one rhythm
often aggravate the other and a pacemaker is often needed.
Atrioventricular conduction block
• First-degree heart block by itself does not require
treatment.
• Second-degree Mobitz type I block (Wenckebach block) is
relatively benign and often transient. If complete block
occurs, the escape pacemaker is situated relatively high
up in the bundle so that the rate is 50–60 per minute with
narrow QRS complexes. Atropine (0.6–1.2 mg
intravenously) is usually effective. Mobitz type II block is
more serious and may progress unpredictably to complete
block with a slow ventricular escape rate. The only
reliable treatment is a pacemaker.
• Third-degree heart block (complete AV dissociation) can
cause cardiac failure and/or attacks of unconsciousness
(Stokes–Adams attacks). Treatment is by electrical pacing;
if delay in arranging this is absolutely unavoidable, lowdose
adrenaline intravenous infusion is sometimes used
as a temporizing measure. Congenital complete heart
block, diagnosed incidentally, does not usually require
treatment.
SELECTED ANTI-DYSRHYTHMIC DRUGS
LIDOCAINE
For more information about lidocaine, see Chapter 24.
Use
Lidocaine is important in the treatment of ventricular tachycardia
and fibrillation, often as an adjunct to DC cardioversion.
An effective plasma concentration is rapidly achieved by giving
a bolus intravenously followed by a constant rate infusion.
Mechanism of action
Lidocaine is a class Ib agent that blocks Na� channels, reducing
the rate of increase of the cardiac action potential and
increasing the effective refractory period. It selectively blocks
open or inactivated channels and dissociates very rapidly.
Adverse effects
These include the following:
SELECTED ANTI-DYSRHYTHMIC DRUGS 223
1. central nervous system – drowsiness, twitching,
paraesthesia, nausea and vomiting; focal followed by
generalized seizures;
2. cardiovascular system – bradycardia, cardiac depression
(negative inotropic effect) and asystole.
Pharmacokinetics
Oral bioavailability is poor because of presystemic metabolism
and lidocaine is given intravenously. It is metabolized in the
liver, its clearance being limited by hepatic blood flow. Heart failure
reduces lidocaine clearance, predisposing to toxicity unless
the dose is reduced. The difference between therapeutic and
toxic plasma concentrations is small. Monoethylglycylxylidide
(MEGX) and glycylxylidide (GX) are active metabolites with less
anti-dysrhythmic action than lidocaine, but with central nervous
system toxicity. The mean half-life of lidocaine is approximately
two hours in healthy subjects.
Drug interactions
Negative inotropes reduce lidocaine clearance by reducing
hepatic blood flow and consequently predispose to accumulation
and toxicity.
OTHER CLASS I DRUGS
Other class I drugs have been widely used in the past, but are
now used much less frequently. Some of these drugs are
shown in Table 32.1.
β-ADRENORECEPTOR ANTAGONISTS
For more information, see also Chapters 28, 29 and 31.
Use
Anti-dysrhythmic properties of β-adrenoceptor antagonists
are useful in the following clinical situations:
• patients who have survived myocardial infarction
(irrespective of any ECG evidence of dysrhythmia);
β-adrenoceptor antagonists prolong life in this
situation;