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9780521704632c14 CUFX213A/Peck 9780521618168 December 28, 2007 12:32
Section IIICardiovascular drugs
Cardiac – following intravenous administration it may produce hypotension,
vasodilatation and a reduced cardiac output. It may also precipitate heart block.
When used to treat SVT the ventricular response rate may increase. It may also
prolong the QT interval and precipitate torsades de pointes.
Non-cardiac – chronically a drug-induced lupus erythematosus syndrome with a
positive anti-nuclear factor develops in 20–30% of patients (many of whom will
be slow acetylators). Other minor effects include gastrointestinal upset, fever and
rash. It reduces the antimicrobial effect of sulphonamides by the production of
para-aminobenzoic acid.Kinetics
Procainamide is well absorbed from the gut and has an oral bioavailability of 75%.
Itsshort half-life of 3 hours necessitates frequent administration or slow release
formulations. It is metabolized in the liver by amidases and by acetylation to the active
N-acetyl procainamide. The latter pathway demonstrates genetic polymorphism so
that patients may be grouped as slow or fast acetylators. The slow acetylators are
more likely to develop side effects.Disopyramide
Disopyramide is a class Ia anti-arrhythmic.Presentation
Itis available as tablets (including slow release) and as a solution containing
10 mg.ml−^1 .The daily oral dose is up to 800 mg in divided doses; the intravenous
dose is 2 mg.kg−^1 over 30 minutes up to 150 mg, which is followed by an infusion of
1 mg.kg−^1 .h−^1 up to 800 mg.day−^1.Uses
Disopyramide is used as a second-line agent in the treatment of both SVT and ven-
tricular tachyarrhythmias. When used to treat atrial fibrillation or atrial flutter the
ventricular rate should first be controlled withβ-blockers or verapamil.Mechanism of action
Disopyramide is a class Ia anti-arrhythmic and as such reduces the rate of rise of
phase 0 of the action potential by blocking Na+channels. In addition, it raises the
threshold potential and prolongs the refractory period, thereby increasing the dura-
tion of the action potential. It also has anticholinergic effects.Side effects
Cardiac – as plasma concentrations rise the QT interval is prolonged (occasionally
precipitating torsades de pointes), myocardial contractility becomes depressed