Biomedical Engineering Reference
In-Depth Information
Nonetheless, it is widely prescribed for this indication, although its severe side
effects on thyroid should not be ignored. Dronedarone, a benzofuran derivative
of Amiodarone [
24
], maintained the multiple electrophysiological properties of
Amiodarone with reduced lipophilic and toxicity features. In the “Dronedarone
Atrial Fibrillation study after Electrical Cardioversion” study, 270 AF patients
were provided dronedarone daily (800, 1,200 or 1,600 mg) versus placebo, but the
significant prolongation of the time to recurrent AF was only observed in 800 mg
group [
25
]. The failure to see the dose-dependent phenomena might be related to the
unwanted gastrointestinal effects at high dosage. However, the spontaneous to sinus
rhythm was 5.8%, 8.2%, and 14.8% in the 800 mg, 1,200 mg, and 1,600 mg groups,
while 3.1% for placebo, which showed a dose-effect correlation. Dronedarone is
now marketed in the USA, Europe, and Canada, providing a safer, better tolerable
modification to Amiodarone for the treatment of atrial disorders.
O
I
O
O
N
CH
3
CH
3
H
3
C
I
Amiodarone
O
N
H
3
C
S
H
3
C
O
O
O
O
N
CH
3
H
3
C
Dronedarone
3.3 K
v
1.5 Potassium Channel Blockers
Current treatment of atrial diseases with Class III antiarrhythmic agents by
blocking
I
Kr
in order to prolong the atrial effective refractory period (AERP)
is often associated with ventricular proarrhythmia because of the excessive
prolongation of ventricular effective refractory period (VERP) and action potential
duration (APD). Therefore, atrial selective strategies were developed. Among
shaker
family
K
v
channels
,
cardiac
K
v
1.5
channel which is the molecular basis for
the human cardiac ultrarapid delayed rectifier potassium current (
I
Kur
) has attracted
much attention. Although
K
v
1.5
gene is also expressed at both mRNA and protein
levels in human ventricle, its functional activities seem to be specific to the atrium,
and the
I
Kur
currents have not yet been recorded in the human ventricle [
26
,
27
].
Therefore, blockade of
I
Kur
may produce an atrial-selective increase in Phase I
