Overview of drug induced hemodynamic, autonomic and
electrophysiological effects
Table 1 allows differentiating two main profiles among torsadogenic
drugs at the first dose level causing either QTc prolongation and/or
increase in HFQT oscillations. The first profile corresponds to drugs
causing non blunted QTc prolongation. All these drugs showed a rapid
onset in QTc prolongation within 1-2 hours after dosing. All the other
torsadogenic drugs exhibited a profile characterised by blunted QTc
prolongation or no QTc prolongation at the first dose showing an
increase in HFQT oscillations. Blunted QTc prolongation was
characterised by a delayed onset in QTc prolongation and delayed peak of
QTc prolongation. 13 out of 15 torsadogenic hERG blocking drugs induced
increases in HFQT oscillations. In addition, 13 experiments were
conducted in combination with atenolol, a β-adrenoceptor blocking drug.
Two non-torsadogenic drugs were also found inducing increases in HFQT
oscillations and reported in the list for comparison: prasozin, an α1
adrenoceptors competitive antagonist and milrinone, a phosphodiesterase
3 inhibitor. Four non torsadogenic hERG blockers (ciprofloxacin,
ranolazine, ebastin, verapamil) presented no QTc prolongation and no
increase in HFQT oscillations at the first dose levels showing
cardiovascular effects and/or changes in autonomic control.