The adrenergic effects of ephedrine shorten cardiac refractory periods, permitting the development of reentrant cardiac arrhythmias. Ephedrine can predispose patients to both hemorrhagic and ischemic stroke. Subarachnoid hemorrhage is thought to be a result of the hypertensive action of ephedrine, which can be short lived, or of cerebral vasculitis, which has been described in association with a variety of sympathomimetic drugs. Thrombotic stroke is presumably related to vasoconstriction of large cerebral arteries, which leads to local thrombosis as a result of stasis and sympathomimetic-induced platelet activation. Caffeine is present in many products that contain ephedra alkaloids, and those who take these products might also be consuming considerable quantities of caffeine in coffee, tea, and soft drinks.
Caffeine is likely to enhance the cardiovascular and central nervous system effects of ephedrine.
Caffeine acts by competitively antagonizing the receptors for adenosine, a hormone released by endothelial cells that dilates blood vessels. By inhibiting adenosine-mediated dilatation of blood vessels, caffeine constricts blood vessels and may increase blood pressure in persons prone to hypertension. Caffeine also augments the release of catecholamines, an effect that, when combined with that of ephedrine, could lead to increased stimulation of the central nervous system and cardiovascular system. Several studies have shown that caffeine and phenylpropanolamine have an additive effect on blood pressure. These interactions between phenylpropanolamine and caffeine support the idea that the combination of ephedrine and caffeine in a dietary supplement could increase the risk of adverse effects.