Drug induced QT interval prolongation
▪️QT interval: the time between the onset of ventricular depolarization (start of the Q wave) and the end of ventricular repolarization (end of the T wave) is called the QT interval.
▪️The definition of a normal QTc varies between sexes but is generally considered < 440 msec. IF a QTc interval >500 ms may be associated with a substantially elevated risk of TdP.
▪️In general, for every 10 ms increase in the QTc interval, there is around a 5–7% increase in the risk of developing TdP(a potentially life-threatening cardiac arrhythmia)
▪️The common causes of a QT interval are electrolyte disturbances, hypothermia, congenital long QT syndrome, and various drugs
▪️Many drug therapies are associated with prolongation of the QT interval. This may increase theTdP.
For example:
– The antipsychotic medication, haloperidol, is a more specific blocker of the IKr potassium channel and prolongs QT (by 15–30 ms) in a dose-dependent manner.
-Antiarrhythmic agents such as quinidine and disopyramide are known to block both the sodium and potassium channels, and are associated with QT interval prolongation. TdP was reported with these drugs at therapeutic or subtherapeutic doses.
-Antiarrhythmics-induced TdP is often precipitated in the presence of hypokalaemia or hypomagnesaemia.
-Tricyclic antidepressants can prolong the QT interval primarily by blocking sodium channels, although this effect is increased if a potassium channel blocker is co-administered
▪️Also,drug -drug i interactions can increase the risk of QT prolongation.
There are three main mechanisms by which this interaction occur:
☆ Pharmacodynamic interactions, when two or more drugs that prolong QT interval are co-prescribed, which can lead to an additive or potentiating effect.
☆ Pharmacokinetic interactions, when a drug that does not prolong the QT interval itself reduces the clearance or is metabolised by the same hepatic enzymes, resulting in increased concentrations of the QT-prolonging drug. for example, ritonavir increases the levels of quinidine by decreasing its metabolism (CYP3A4 inhibitor).
☆ Drug-induced electrolyte imbalances, such as hypokalaemia and hypomagnesaemia, which can increase the risk of QT prolongation. for example, loop or thiazide diuretics causing hypokalaemia.
Reference:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237186/
