Despite its long history of use as an active ingredient in herbal supplements (e.g. Ma huang) ephedrine has not been well studied in humans.
Classically considered to exert its effects primarily by an indirect “tyramine-like” sympathomimetic mechanism , since it exhibits tachyphylaxis (acute tolerance) when administered repeatidly.
More recent studies indicate that, ephedrine also exerts direct effects (at least in rats & mice) that are mediated by direct stimulation of adrenergic receptors (Liles et al, 2006; 2007), and/or trace amine-associated receptors (e.g. TAAR1) (Broadley, 2010).
A cardinal characteristic of mixed-acting sympathomimetics is that their effects are blunted, but not abolished, by prior treatment with drugs that deplete presynaptic stores of catecholamines (e.g. pre-treatment with reserpine or guanethidine)(Westfall & Westfall, 2011).
Ephedrine i.v. produces a more favorable prolonged pressor response compared to phenylephrine , accompanied by a sustained increase in heart rate, stroke volume & cardiac index when administered to patients under general anesthesia (Table 1)(Xia et al, 2016).
NOTE: The FDA banned the sale of “ephedra” herbal supplements containing measurable levels of ephedrine in 2004 due to an increased risk of stroke, myocardial infarction and sudden death (see ma-huang_ephedra).
| TABLE 1: Duration of Hemodynamic Effects of IV Injections of Ephedrine & Phenylephrine in Anesthetized Patients* | ||||
|---|---|---|---|---|
| Drug | Mean Arterial BP | Heart Rate | Stroke Volume | Cardiac Output |
| Ephedrine | 10 min increase | 10 min increase | 8 min increase | 10 min increase |
| Phenylephrine | 6 min increase | 2 min decrease | 4 min increase | 3 min increase |
* Results from a randomized double blinded study comparing the duration of hemodynamic responses to ephedrine and phenylephrine in patients undergoing lumbar spinal surgery while under propofol general anesthesia. The table shows the duration of significant increases or decreases in hemodynamic parameters compared to baseline (P
With chronic repetitive use: increased incidence of myocardial infarction, stroke and sudden death (e.g. associated with chronic use of ephedrine-containing herbal supplements)
Hypertension, insomniaEphedrine occurs in various plants and is the active ingredient in Ma-huang , a popular herbal medication
In Dec 2003, the FDA issued a consumer alert to alert consumers to immediately stop buying and using ephedra products. The alert was based mainly upon a review of recent adverse event reports that indicated an increased risk of stroke, myocardial infarction and sudden death in those using ephedra containing dietary supplements. The FDA also announced a plan to ban the sale of all food supplements containing ephedrine in the near future.
Broadley KJ (2010): The vascular effects of trace amines and amphetamines. Pharmacol Ther. 125(3):363-75. doi: 10.1016/j.pharmthera.2009.11.005.
Liles JT et al (2006): Pressor responses to ephedrine are mediated by a direct mechanism in the rat. J Pharmacol Exp Ther. 316(1):95-105. DOI:10.1124/jpet.105.090035
Liles JT et al (2007): Pressor responses to ephedrine are not impaired in dopamine beta-hydroxylase knockout mice. Br J Pharmacol. 150(1):29-36. DOI: 10.1038/sj.bjp.0706942
Westfall TC, Westfall DP (2011): Adrenergic agonists and antagonists. Chapter 12. In: Goodman & Gilman's The Pharmacological Basis of Therapeutics. 12th Ed. McGraw-Hill.
Xia J et al (2016): Hemodynamic effects of ephedrine and phenylephrine bolus injection in patients in the prone position under general anesthesia for lumbar spinal surgery. Experimental and therapeutic medicine. 12(2):1141-1146. DOI: 10.3892/etm.2016.3432; PMID: 27446334
