Ketanserin Diuretics

Ketanserin (25) is an antihypertensive agent acting as an antagonist at both the serotonin-S2 and Qj-adrencrgic receptors [22]. Bendroflumethiazide (26) is the most notable in a class of diuretic-antihypertensive agents [5]... 

Ketanserin should not be combined with drugs that prolong the QT interval, e.g. class la anti-arrhythmics, amiodarone, sotalol, erythromycin. The risk of torsade de pointes secondary to hypokalaemia is increased when ketanserin is combined with thiazides or loop diuretics without concomitant use of a potassium-sparing diuretic or an angiotensin-converting enzyme (ACE) inhibitor, a 1 Antagonists... 

Several uracil derivatives have been developed as drugs. Thus, methyl-thiouracil and propylthiouracil are thyroid inhibitors Bucolome is an antiinflammatory and Uramustine (Uracil Mustard), Fluorouracil, and its masked compounds are anticancer agents. Aminometradine and Amiso-metradine are used clinically as diuretics, and Urapidil and Ketanserin are used as antihypertensives (Scheme 5). 

Prolongation of the QT interval by ketanserin is more pronounced when it used in combination with potassium-wasting diuretics (4). This combination must therefore be avoided. 

Sudden deaths, probably from cardiac arrhythmias, were markedly Increased In patients taking potassium-depleting diuretics and high doses of ketanserin. No interaction occurred with low doses of ketanserin in those with normal potassium levels. Potassium-sparing diuretics do not interact in this way. 

Potassium-depleting diuretics may cause hypokalaemia, which increases the risk of QT-prolongation and torsade de pointes arrhythmia, which can result in sudden death. Ketanserin also prolongs the QT interval in a dose-related way, and its effects would be expected to be additive with that of diuretic-induced hypokalaemia. See also Drugs that prolong the QT interval + Other drugs that prolong the QT interval , p.257. 

The use of potassium-depleting diuretics (see Table 26.1 (p.944)) with ketanserin 40 mg three times daily should be avoided. Lower doses of ketanserin (20 mg twice daily) have less effect on the QT interval, and can probably be used cautiously with potassium-depleting diuretics, as long as serum potassium levels are maintained. Potassium-sparing diuretics do not interact. 

VanGoolR, Symoens J. Ketanserin in combination witii diuretics effect on QTc-interval.Ewr Heart J (1990) 11 (Suppl), 57. 

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