QTc Prolongation

Adenosine is used in pharmacologic cardiac stress testing. 

Accepted alternative agents include regadenoson (effects correlated with AMP deaminase polymorphisms: PMID 26554440) and dipyridamole (inhibits adenosine deaminase: PMID 6628545). It may be that both agents inhibit both enzymes: either/both are expected to increase adenosine.

Both regadenoson and dipyridamole share a non-physiologic 2,6 di-amino structure.

Adenosine causes QTc prolongation in patients with cardiac disease: PMID 7744540.  This is consistent with the broader literature that QTc prolongation is a marker for cardiac risk, rather than an independent problem to be addressed: PMID 25168784.

Among psychiatric medications, ziprasidone and citalopram are commonly associated with QTc prolongation. 

These drugs share a 2-halide/pseudohalide structure with cladribine (more here). Cladribine has recognized mechanism of action as an adenosine deaminase inhibitor PMID 21463108. These medications may act similarly, increasing available adenosine.

Increased adenosine may be a shared mechanism of QTc prolongation associated with psychiatric medications.

Risperidone is among the most frequently cited psychotropics in case reports of torsades de pointes (TdP), the feared arrhythmia attributed to prolonged QTc: PMID 25168784. Fluoride, chloride, and pseudohalides are often interchangeable at the active binding site, typically with decreasing effect, consistent with limited available TdP frequency information. 

Risperidone QTc screening may be advisable based on TdP case reports and chemical structure.

Risk of QTc prolongation between citalopram and escitalopram is comparable: PMID 23791140. 

There are not yet reports of vilazodone QTc prolongation with, but it shares likely active site (2-pseudohalide) with escitalopram/ citalopram.

Some patients report mild chest pain and/or demonstrate an acute decrease in blood pressure upon starting a QTc-prolonging psychiatric medication, consistent with cardiac effects of increased adenosine. Similar to side effects from a single dose of adenosine, these typically resolve spontaneously. It is not clear whether a side-effect of temporary chest pain may indicate increased cardiac risk.

Cardiac stress testing depends on peripheral vasodilation.

Several peripheral vasodilators are without broadly accepted mechanism of action and are strikingly adenosine-similar: they may act by inhibiting adenosine metabolism or directly activating the adenosine receptor.