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9780521704632c14 CUFX213A/Peck 9780521618168 December 28, 2007 12:32
Section IIICardiovascular drugsSide effects
Although esmolol is relatively cardioselective it does demonstrateβ 2 -adrenoceptor
antagonism at high doses and should therefore be used with caution in asthmatics.
Like otherβ-blockers it may also precipitate heart failure. However, due to its short
duration of action these side effects are also limited in time.
Itis irritant to veins and extravasation may lead to tissue necrosis.Kinetics
Esmolol is only available intravenously and is 60% plasma protein bound. Its volume
of distribution is 3.5 l.kg−^1 .Itisrapidly metabolized by red blood cell esterases to
an essentially inactive acid metabolite (with a long half-life) and methyl alcohol. Its
rapid metabolism ensures a short half-life of 10 minutes. The esterases responsible
for its hydrolysis are distinct from plasma cholinesterase so that it does not prolong
the actions of suxamethonium.Quinidine
The use of quinidine has declined as alternative treatments have become available
with improved side-effect profiles. However, it may still be used to treat SVT, including
atrial fibrillation and flutter, and ventricular ectopic beats.Mechanism of action
Quinidine 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 without affecting the duration of the
action potential. It also antagonizes vagal tone.Side effects
These are common and become unacceptable in up to 30% of patients.
Cardiac – quinidine may provoke other arrhythmias including heart block, sinus
tachycardia (vagolytic action) and ventricular arrhythmias. The following ECG
changes may be seen: prolonged PR interval, widened QRS and prolonged QT inter-
val. When used to treat atrial fibrillation or flutter the patient should be pretreated
withβ-blockers, Ca^2 +channel antagonists or digoxin to slow AV conduction, which
may otherwise become enhanced leading to a ventricular rate equivalent to the
atrial rate. Hypotension may result fromα-blockade or direct myocardial depres-
sion, which is exacerbated by hyperkalaemia.
Non-cardiac – central nervous system toxicity known as ‘cinchonism’ is
characterized by tinnitus, blurred vision, impaired hearing, headache and
confusion.
Drug interactions – digoxin is displaced from its binding sites so that its serum con-
centration is increased. Phenytoin will reduce quinidine levels (hepatic enzyme