Chloroquine and hydroxychloroquine side effects on
cardiovascular system
Another essential aspect to be discussed is about chloroquine
cardiovascular side effects since this is one of the promising drugs
that have been tested in COVID-19 patients. It is well-reported that
long-term chloroquine use may increase depolarization length duration
and Purkinje fiber\souts refractory period31-34,
ultimately leading to atrioventricular nodal and/or His system
malfunction31.
As an antimalarial drug, both chloroquine and hydroxychloroquine (HCQ)
are accumulated in lysosomes, directly inhibiting phospholipase
activity, inducing cytoplasmic inclusion body formation, increasing
lysosomal pH and causing protein inactivity31,35. Due
to these properties, drug-induced atrial and ventricular arrhythmias
have been associated with their use31-35. The most
usual electrocardiographic alteration is fascicular block, which can
lead to advanced types of atrioventricular block, generally associated
with syncope36.
HCQ can also induce QT interval prolongation, an extremely rare but
potential fatal side effect, due to the risk of induced polymorphic
ventricular tachycardia and SCD. The proposed mechanism by which HCQ
causes QT interval prolongation is not well understood. In 2015, Capel
et al. demonstrated, in guinea pig sinoatrial node myocytes, an
inhibitory effect of the HCQ on the hyperpolarization-activated current
ion channels (also known as “funny current” channels), along with
delayed rectifier potassium currents, and L-type calcium ion
currents37. Inhibitory effects on pacemaker cells were
shown to cause delayed rates in depolarization leading to decreased
heart rates. These findings may correlate with a proposed mechanism by
which refractory action potentials in cardiac myocytes may lead to
prolongation of QT interval due to delayed depolarization and
repolarization from abnormal ion currents38. QT
prolongation in individual medical therapy is not always predictable,
dose adjustments and/or additional monitoring of electrocardiograms may
be appropriate in some cases. HCQ proarrhythmic risk must be monitored
in patients with underlying cardiovascular or renal disorders, and high
caution should be posed in the case of electrolyte imbalance,
dysrhythmias or concurrent use
of QTc-prolonging drugs38.