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 fur-
ther episodes and/or serious ventricular dysrhythmias remain
inducible on electrophysiological testing.
Ventricular fibrillation: See above under Advanced life sup-
port. As discussed above for ventricular tachycardia, implant-
ation 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.Discontinuedigoxin, beta-blockers, verapamilor other
   drugs that exacerbate bradycardia.
   4.Pacemaker insertion is indicated if bradycardia is
   unresponsive to atropineand 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, low-
  doseadrenalineintravenous 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

Lidocaineis important in the treatment of ventricular tachy-

cardia and fibrillation, often as an adjunct to DC cardioversion.

An effective plasma concentration is rapidly achieved by giv-

ing a bolus intravenously followed by a constant rate infusion.

Mechanism of action

Lidocaineis a class Ib agent that blocks Nachannels, redu-

cing 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:

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

andlidocaineis given intravenously. It is metabolized in the

liver, its clearance being limited by hepatic blood flow. Heart fail-

ure reduces lidocaineclearance, 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 lidocaineis approximately

two hours in healthy subjects.

Drug interactions

Negative inotropes reduce lidocaineclearance by reducing

hepatic blood flow and consequently predispose to accumula-

tion 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;

SELECTEDANTI-DYSRHYTHMICDRUGS 223