Ephedrine

Brand Names: Claritin-D, Sudafed

Clinical Names: Ephedrine, Pseudoephedrine

Summary

generic names: Ephedrine, Pseudoephedrine

trade names: Pseudoephedrine is an ingredient in many pharmaceutical and over-the-counter substances, including Sudafed® and Claritin-D®, an antihistamine.

type of drug:
• Ephedrine: sympathomimetic, bronchodilator
• Pseudoephedrine: decongestant

used to treat:
• Ephedrine: asthma
• Pseudoephedrine: nasal congestion

overview of interactions:
• herb group possibly affecting drug performance: Salicylate-containing Herbs such as Betula lenta (Sweet Birch bark), Cimicifuga racemosa (Black Cohosh rhizome), Filipendula ulmaria (Meadowsweet flower), Gaultheria procumbens (Wintergreen leaves), Populus canadensis (Poplar bark and/or buds), and Salix spp. (Willow bark)

• herb group possibly affecting drug performance: Herbs containing Tannins such as Camellia sinensis (Green Tea and Black Tea), Arctostaphylos uva-ursi (Uva ursi), Juglans nigra (Black Walnut), Rubus idaeus (Red Raspberry), Quercus spp. (Oak), and Hamamelis virginiana (Witch Hazel)

• herb(s) amplifying drug action: Ephedra sinica (Ma Huang, Chinese Ephedra, Chinese jointfir) or Ephedra gerardiana (Indian jointfir)

• substances affecting drug toxicity: Pharmaceutical MAOI (Monoamine Oxidase Inhibitor) substances, such as Eutonyl (pargyline), Furoxone (furazolidone), Laniazid, Marplan (isocarboxazid), Matulane (procarbazine), Nardil (phenelzine), Nydrazid, Parnate (tranylcypromine), Rifamate, Rimactane/INH, moclobemide, Selegiline (deprenyl), and tranycypromine, are known to interact with ephedrine and pseudoephedrine; there is also at least the theoretical possibility that herbs often considered as having actions similar to MAOI's such as Hypericum perforatum (St. John's Wort), might also.





Interactions

herb group possibly affecting drug performance: Salicylate-containing Herbs such as Betula lenta (Sweet Birch bark), Cimicifuga racemosa (Black Cohosh rhizome), Filipendula ulmaria (Meadowsweet flower), Gaultheria procumbens (Wintergreen leaves), Populus canadensis (Poplar bark and/or buds), and Salix spp. (Willow bark)

• mechanism: Herbs high in salicylates (aspirin-like compounds) can precipitate alkaloids and could impair absorption of ephedrine and pseudoephedrine.
(Brinker F. J Naturopathic Med 1997;7(2):14-20; Brinker F. 96, 99-100, 1997.)

• herbal concerns: Herbs high in salicylates should not be taken concurrently with prescribed ephedrine or pseudoephedrine.

herb group possibly affecting drug performance: Herbs containing Tannins such as Camellia sinensis (Green Tea and Black Tea), Arctostaphylos uva-ursi (Uva ursi), Juglans nigra (Black Walnut), Rubus idaeus (Red Raspberry), Quercus spp. (Oak), and Hamamelis virginiana (Witch Hazel)

• mechanism: Herbs high which yield tannins when extracted by hot water can precipitate alkaloids which can impair absorption of ephedrine and pseudoephedrine. Tannins will not precipitate low concentrations of alkaloidal salts in the presence of many gums present in plants such as Acacia, Agar, Aloe, Flax, Guar, Irish moss, Locust bean, Marshmallow root, Okra fruit, pectin powder, Psyllium seed husks and Slippery Elm bar.
(Brinker F. J Naturopathic Med 1997;7(2):14-20; Brinker F. 99-100, 1997.)

• herbal concerns: Herbs high in tannins should not be taken concurrently with prescribed ephedrine or pseudoephedrine. 

herb(s) amplifying drug action: Ephedra sinica (Ma Huang, Chinese Ephedra, Chinese jointfir) or Ephedra gerardiana (Indian jointfir)

• mechanism: The Chinese herb Ephedra and closely related species contain the alkaloids ephedrine and pseudoephedrine and should not be combined with prescription ephedrine or with pseudoephedrine.
Note: Ephedra nevadensis (Mormon tea) contains little or no alkaloids and thus does not interact with pharmaceutical ephedrine and pseudoephedrine as would the Chinese Ephedra sinica.
(Noguchi M, et al. Yakugaku Zasshi. 1978 Jul;98(7):923-928.)

substances affecting drug toxicity: Pharmaceutical MAOI (Monoamine Oxidase Inhibitor) substances, such as Eutonyl (pargyline), Furoxone (furazolidone), Laniazid, Marplan (isocarboxazid), Matulane (procarbazine), Nardil (phenelzine), Nydrazid, Parnate (tranylcypromine), Rifamate, Rimactane/INH, moclobemide, Selegiline (deprenyl), and tranycypromine, are known to interact with ephedrine and pseudoephedrine; there is also at least the theoretical possibility that herbs often considered as having actions similar to MAOI's such as Hypericum perforatum (St. John's Wort), might also.

• mechanisms:
» Ephedrine and norepinephrine (noradrenaline in the UK) are both metabolized in part by MAO. Thus, at least theoretically pharmaceutical ephedrine and pseudoephedrine might interact with Hypericum and other herbs regarded as MAOI. Although St. John's Wort (SJW) has been regarded as a MAOI, the MAOI effect of Hypericum is not large enough to account for an antidepressant action based on this effect. Current research indicates inhibition of reuptake of dopamine, serotonin, and norepinephrine to be the acute effects that lead to receptor adaptive changes that produce the antidepressant effect. This presents the theoretical possibility of SJW potentiating the effect of norepinephrine, albeit through a mechanism different than MAOI. At this point any concern regarding an interaction between Hypericum and ephedrine or pseudoephedrine is merely theoretical and no cases have been reported in the scientific literature. The reported pharmacological effects of many herbs are based on assays that may have little if any clinical relevance. (Dentali)

» Ephedrine can induce toxicity from monoamine oxidase inhibitors (MAOI) due to increased release of noradrenaline by ephedrine, even after stopping the MAOI medication and should not for at least two weeks after stopping the MAOI.
(Brinker F. 63, 1997; Dingemanse J. Int Clin Psychopharmacol 1993 Jan;7(3-4):167-180; Holzl J, et al. Planta Med 55:643, 1989; Lefebvre H, et al. Clin Endocrinol (Oxf) 1995 Jan;42(1):95-98; Dawson JK, et al. J Accid Emerg Med 1995 Mar;12(1):49-51.)
Note: The interaction with ephedrine is a more definite concern with pharmaceutical MAOI (monoamine oxidase-inhibiting ) substances than with herbs such as Hypericum (St. John's Wort).
(Simpson LL. J Pharmacol Exp Ther. 1978 May;205(2):392-399.)
» Monoamine oxidase inhibitors and pseudoephedrine could interact to cause a hypertensive crisis.
(Meletis C, Jacobs T. 8, 1996.)

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References

Blumenthal M, King P. Ma huang: ancient herb, modem medicine, regulatory dilemma. HerbalGram. No. 35, pp.22-26,43,56-57, 1995.

Brinker F. Interactions of pharmaceutical and botanical medicines. J Naturopathic Med 1997;7(2):14-20.

Brinker Francis. Herb Contraindications and Drug Interactions. Sandy, OR: Eclectic Institute, Inc., 1997.

Dawson JK, Earnshaw SM, Graham CS. Dangerous monoamine oxidase inhibitor interactions are still occurring in the 1990s. J Accid Emerg Med 1995 Mar;12(1):49-51.
Abstract: The clinical course is described of a 28-year-old woman who was severely ill following ingestion of a Do-Do tablet (which consists of ephedrine, caffeine and theophylline), 24 h after discontinuing phenelzine treatment. Signs and symptoms were delayed for 8 h after which she developed encephalopathy, neuromuscular irritability, hypotension, sinus tachycardia, rhabdomyolysis and hyperthermia. Her illness was complicated by pneumonia and adult respiratory distress syndrome (ARDS). The management of monoamine oxidase inhibitor (MAOI) toxicity, which can arise from interactions and overdoses, is discussed. It should be remembered that, despite the increase in use of alternative and safer antidepressants, MAOI interactions still occur and unless they are managed appropriately, are potentially fatal. Patients need to be warned that restrictions apply for up to 2 weeks after stopping the medication, and doctors need to be aware that serious interactions can occur in this time period.

Dentali S. Dentali Associates: Natural Products Consulting Services, Troutdale, OR.

Dingemanse J. An update of recent moclobemide interaction data. Int Clin Psychopharmacol 1993 Jan;7(3-4):167-180.
Abstract: The classical monoamine oxidase inhibitors (MAOIs) are believed to have serious risks because of interactions with other drugs and foodstuffs, although not with a sound scientific basis in all cases. However, moclobemide, a selective reversible inhibitor of MAO-A, has a low propensity for producing drug interactions. Interaction studies have been carried out in healthy volunteers in an attempt to answer some relevant practical questions related to therapy with moclobemide. In combination with therapeutic doses of either fluvoxamine or fluoxetine, moclobemide did not provide any indication of a serotoninergic syndrome, so that no wash-out period is needed when switching from a selective serotonin re-uptake inhibitor to moclobemide or vice versa. Since concomitant treatment with moclobemide and selegiline had a supra-additive effect on the sensitivity to intravenously administered tyramine, that combination therapy should only be considered when accompanied by dietary restrictions. Concomitant treatment with moclobemide and levodopa/benserazide, however, was well tolerated. When oral ephedrine was added to steady-state moclobemide treatment, the cardiovascular effects of the former were increased to about the same extent as for oral tyramine, i.e. a potentiation of 2-4.

Holzl J, Demisch L, Gollnik B. Investigations about Antidepressive and Mood Changing Effects of Hypericum perforatum. Planta Med 55:643, 1989.

Kooy A, Peters-Romeyn BM, van Gool AR. [Monoamine oxidase inhibitors: poisoning and interactions]. Ned Tijdschr Geneeskd 1993 Sep 18;137(38):1910-1914. [Article in Dutch]

Lefebvre H, Noblet C, Moore N, Wolf LM. Pseudo-phaeochromocytoma after multiple drug interactions involving the selective monoamine oxidase inhibitor selegiline. Clin Endocrinol (Oxf) 1995 Jan;42(1):95-98.
Abstract: A patient presented with paroxysmal hypertension and typical clinical features of phaeochromocytoma, but with a normal adrenal computed tomographic scan and much higher plasma noradrenaline than adrenaline concentrations. Urinary vanillylmandelic acid concentrations were only moderately elevated. This syndrome probably arose as a consequence of an interaction between the monoamine oxidase inhibitor selegiline, the sympathomimetic agent ephedrine, and a tricyclic antidepressant. The mechanism of the interaction is thought to be related to increased sympathetic release of noradrenaline by ephedrine, inhibition of catabolism by selegiline, and inhibition of reuptake of noradrenaline by the tricyclic. Although newer selective monoamine oxidase inhibitors are considered to be safer than earlier non-selective inhibitors, they can also contribute to drug interactions mimicking phaeochromocytoma.

Meletis C, Jacobs T. The Practitioner's Guide to Drug-Nutrient and Nutrient-Nutrient Interactions. Portland, OR: Self-published, 1996.

Noguchi M, Kubo M, Naka Y. [Studies on the pharmaceutical quality evaluation of crude drug preparations used in Orient medicine "Kampoo". IV. Behavior of alkaloids in ephedra herb mixed with other crude drugs under decoction processes]. Yakugaku Zasshi. 1978 Jul;98(7):923-928. [Article in Japanese]

Simpson G. "Cold" cures and monoamine-oxidase inhibitors. Br Med J 1969 Jun 7;2(657):635.

Simpson LL. Mechanism of the adverse interaction between monoamine oxidase inhibitors and amphetamine. J Pharmacol Exp Ther. 1978 May;205(2):392-399.

Sparenberg B, Demisch L, Hoelzl J. Antidepressive constituents of St. Johnswort. PZ Wiss 1993;6:50-54. (C.A. 119:85914z)

Willard T. The Interactive Herbal. 1998. Calgary, Alberta: Follgard Group/CD•Visions.