Biomedical Engineering Reference
In-Depth Information
arrhythmias) of QT prolongation and ventricular tachyarrhythmia have been
reported with pimozide by Committee on Safety of Medicines from 1971 to
1995, which is a potent neuroleptic useful in the management of motor and phonic
tics associated with Tourette syndrome. The effects of pimozide on monophasic
action potential duration were increased and concentration-dependent block of the
rapid component of the delayed rectifier potassium current and tail current was
decreased [
106
-
109
]. Pimozide possesses cardiac electrophysiological effects sim-
ilar to those of class III antiarrhythmic drugs (Table
2
). These effects are concen-
tration dependent and observed at recommended dosages of the drug. Since
pimozide is strongly metabolized by CYP3A4, special care should be taken to
avoid potential pharmacokinetic interactions leading to high plasma levels of
pimozide and proarrhythmia.
Prenylamine: It is a calcium channel blocker, which is used as a vasodilator in
the treatment of angina pectoris. It has been shown to partially metabolize to
amphetamine and can cause false positives for it in drug tests. Prenylamine also
appears to act as a vesicular monoamine transporter inhibitor and has been
demonstrated to deplete vesicular monoamine neurotransmitter stores similarly to
reserpine (Table
2
). It is well known fact that long use of prenylamine causes
LQTS, ventricular premature beats and short run of ventricular tachyarrhthmia with
Tdp
pattern [
110
].
Risperidone: It is commonly used for the treatment of psychosis. Risperidone
exerts antagonistic effects on 5-hydroxytryptamine (5-HT
2
), dopamine (D
2
),
a
-adrenoceptors and histamine (H
1
) receptors. In contrast with other antipsychotics
such as haloperidol and chlorpromazine, it allows a clear improvement of the
quality of life of patients by a reduction in specific extrapyramidal effects [
111
].
Risperidone has been implicated in several cases of QT interval lengthening, the
majority of them occurring with risperidone over-dosage [
112
]. However, to our
knowledge, no case of
Tdp
was reported with risperidone at therapeutic doses. In
most of the cases, QT prolongation by non-cardiac drugs such as risperidone
involved a reduction of repolarizing K
+
currents, particularly the rapid component
of delayed rectifier current IK
r
. At cellular level, this results in prolongation of
cardiac action potential duration [
113
]; 0.3 mM risperidone reduced by about 50%
the IK
r
current in rabbit ventricular myocytes and 0.1 mM risperidone lengthened
significantly action potential duration recorded both in rabbit Purkinje fiber and in
ventricular myocardium [
114
,
115
]; 3 mM risperidone prolongs the action potential
duration at 90% repolarization recorded in ventricular guinea pigs myocardium by
about 27% [
116
] and 10 mM risperidone also prolonged the final action potential
repolarization by about 20% in guinea pigs papillary muscle and by about 10%
in isolated cardiac canine myocyte, concurrently with a reduction of IK
r
current
[
117
,
118
]. In
hERG
cloned channel that expresses K
+
channel underlying IK
r
in
human heart, risperidone showed blockade of this channel at IC
50
value of 1.6
M,
m
0.39
M[
119
]. IK
r
and IK
s
have also been described in human atrial
myocyte [
120
] but not in all myocytes and with only relatively small densities in
comparison with the densities of potassium currents. In clinical practice, adverse
effects of QT prolonging drugs can be prevented by not exceeding the
M, and 0.15
m
m
