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Section IIICardiovascular drugsKinetics
When used for the treatment of arrhythmias lidocaine is only given intravenously. It
is 33% unionized and 70% protein bound. It is metabolized by hepatic amidases to
products that are eliminated in the urine. Its elimination half-life is about 90 minutes
so that in the presence of normal hepatic function a steady-state would be reached
after about 6 hours in the absence of a loading dose. Its clearance is reduced in
cardiac failure due to reduced hepatic blood flow.Mexiletine
Mexiletine is an analogue of lidocaine with similar effects on ventricular tach-
yarrhythmias.Presentation
Itis presented as a colourless solution containing 250 mg mexiletine hydrochloride
in 10 ml. The oral formulation is also available as modified release.Uses
Mexiletine has similar indications to lidocaine particularly when arrhythmias are
associated with ischaemia or digoxin.Mechanism of action
Mexiletine reduces the rate of rise of phase 0 of the action potential by blocking Na+
channels and raising the threshold potential. The duration of the action potential
and the refractory period are decreased as the repolarization phase 3 is shortened.Side effects
Mexiletine has a low therapeutic ratio and side effects are common.
Cardiac – it may precipitate sinus bradycardia, supraventricular and ventricular
tachyarrhythmias.
Non-cardiac – up to 40% of patients have unacceptable nausea and vomiting and
altered bowel habit. Confusion, diplopia, seizures, tremor and ataxia are also seen.
Thrombocytopenia, rash and jaundice have also been reported.Kinetics
Itsoralbioavailability of 90% reflects good absorption from the upper part of the
small bowel and minimal first-pass metabolism (about 10%). It is 65% plasma pro-
tein bound and has a volume of distribution of 6–13 l.kg−^1 .Itundergoes hepatic
metabolism to a number of inactive metabolites. Up to 20% is excreted unchanged
in the urine.