As pleurisy root and other plants in the Aesclepius genus contain cardiac glycosides, it is best to avoid use of pleurisy root with heart medications such as beta-blockers.

Some beta-adrenergic blockers (called “nonselective” beta blockers) decrease the uptake of potassium from the blood into the cells, leading to excess potassium in the blood, a potentially dangerous condition known as hyperkalemia. People taking beta-blockers should therefore avoid taking potassium supplements, or eating large quantities of fruit (for example, bananas), unless directed to do so by their doctor.

In a study of healthy volunteers, drinking 200 ml of grapefruit juice at the same time as taking acebutolol caused a small decrease in blood levels of the drug by interfering with its absorption. Although the researchers who performed this study felt that the effect was unlikely to be clinically significant in most cases, it would seem prudent not to take grapefruit juice at the same time as acebutolol.