Ephedrine cardiovascular effect

Interest in ephedrine in Western medicine was created by the classical investigations of Chen and Schmidt, which began in 1923 as a result of a Chinese druggist s assurance that ma huang was really a potent drug. These workers reported the cardiovascular effects of the alkaloid, its similarity to epinephrine, and its absorption from the intestinal tract. Numerous clinical and experimental studies soon followed, and the use of ephedrine spread so rapidly that several tons of the alkaloid are now consumed yearly. Synthetic ephedrine (racemic) was first prepared in 1927 and marketed under the name Ephetonin (Goodman and Gilman, 1955). 

The cardiovascular effects, subjective effects, and abuse potential of single intranasal doses of ephedrine 5 and 10 mg have been compared with oral doses of (—)ephe-drine 50 mg in 16 healthy Caucasian men with no drug/ alcohol/nicotine abuse or dependence (5). Intranasal ephedrine caused an increase in blood pressure but associated orthostatic hypotension. 

Tricyclic antidepressants inhibit the uptake of catecholamines, such as ephedrine, into sympathetic neurons and can enhance their cardiovascular effects (41). 

Tashkin DP, Meth R, Simmons DH, Lee YE. Double-blind comparison of acute bronchial and cardiovascular effects of oral terbutaline and ephedrine. Chest 1975 68(2) 155—161. 

Dingemanse J, Guentert T, Gieschke R, Stabl M. Modification of the cardiovascular effects of ephedrine by the reversible monoamine oxidase A-inhibitor moclobemide. J Cardiovasc Pharmacol 1996 28(6) 856—861. 

Waluga M, Janusz M, et al. Cardiovascular effects of ephedrine, caffeine, and yohimbine measured by thoracic electrical bioimpedance in obese women. Clin Physiol 1998 18 6976. 

Maichei, E., M. Pellegrini, R. Pacifici, P. Zuccaro, and S. Pichini. 2006. A rapid and simple procedure for the determination of ephedrine alkaloids in dietary supplements by gas chromatography-mass Sf>ectiometry. /. Pharm. Burned. Anal. 41(5) 1633-1641. Medeiros, I.A., M.R. Santos, N.M. Nascimento, and J.C. Duarte. 2006. Cardiovascular effects of Sida cordifolia leaves extract in rats. Fitoterapia 77(l) 19-27. 

Chemical Structures. Figure 1 shows the chemical structures for 14 phenylethylamine compounds. Nine of these compounds are used clinically as anorectics (ii-amphetamine, phentermine, diethylpropion, phenmetrazine, phendimetrazine, clotermine, chlorphentermine, benzphetamine, and fenfluramine). Four of these compounds are not approved for clinical use and are reported to have hallucinogenic properties (MDA, PMA, DOM, and DOET). The final compound ( /-ephedrine) is used clinically for bronchial muscle relaxation, cardiovascular, and mydriatic effects. Figure 2 shows the chemical structure for MDMA, the methyl analog of MDA. MDMA is not approved for clinical use and has been reported to produce both LSD-like and cocaine-like effects. 

Ephedra (ma huang) is a popular botanical incorporated into a variety of formulations for weight loss, energy or performance enhancement, and symptomatic control of asthma. A pharmacodynamic interaction leading to a fatality has been reported with concurrent use of caffeine and ephedra (62), possibly as a result of additive adrenergic agonist effect of the ephedrine alkaloids and caffeine on the cardiovascular system and the CNS (63). Ephedra was recently withdrawn from the market (64). 

Cardiovascular toxicity is also frequently encountered in poisoning. Hypotension may be due to depression of cardiac contractility hypovolemia resulting from vomiting, diarrhea, or fluid sequestration peripheral vascular collapse due to blockade of -adrenoceptor-mediated vascular tone or cardiac arrhythmias. Hypothermia or hyperthermia due to exposure as well as the temperature-dysregulating effects of many drugs can also produce hypotension. Lethal arrhythmias such as ventricular tachycardia and fibrillation can occur with overdoses of many cardioactive drugs such as ephedrine, amphetamines, cocaine, tricyclic antidepressants, digitalis, and theophylline. 

Non-selective beta-agonists (ephedrine, orciprenaline) are now rarely used because of the higher incidence of cardiovascular side-effects by their action on beta-1 receptors... 

The authors suggested that even the small amounts of ephedrine present as additives in some local anesthetics can have a marked effect on the cardiovascular system. 

Many cases of serious adverse effects and even fatalities have been reported that were linked with ephedra or ephedrine administration over the last 10 years. Haller and Benowitz published a review of 140 reports of adverse events related to the use of ephedra alkaloids that were submitted to the FDA between June 1997 and March 1999. Using standardized rating system for assessing causation, 31% of the cases were considered to be definitely or probably related to the use of ephedra alkaloid-containing supplements, and another 31% were deemed to be possibly related. Among these adverse events, 47% involved in cardiovascular symptoms and 18% involved the CNS. Hypertension was the most frequent adverse effect, followed by palpitations, tachycardia, or both stroke and seizures. Ten events led to death and 13 cases produced permanent disability. 

Studies have shown that resultant effects are similar, regardless of whether pure synthetic ephedrine or naturally occurring ephedra is ingested (24,25). There are,however, significant enantioselective differences between the enantomers in both pharmacokinetic and pharmacodynamic effects. All of the ephedra alkaloids have important effects on the cardiovascular and respiratory systems, but not to the same degree. 

An article in the Canadian Adverse Reaction Newsletter published their reporting of adverse effects caused by products containing C. aurantium from January 1, 1998 to February 28, 2004 (46). The article lists 16 reports of synephrine associated with cardiovascular events including tachycardia, cardiac arrest, ventricular fibrillation, transient collapse, and blackout. In one case, bitter orange was the sole suspected culprit. In seven others the products also contained caffeine, and in eight cases the product contained both caffeine and ephedrine. Health Canada has issued an advisory stating that synephrine may have effects similar to ephedrine and caution should be used if taking it (47). 

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