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EPHEDRACEAE

(Joint-Pine family)

 

This family of 40 species in one genus occurs in northern and southern warm temperate regions (Mabberley 1987). Ephedras were at one time classified in the Gnetaceae.

Ephedras are the source of Ma Huang, which has been used medicinally in China for about 5000 years. It is derived from Ephedra equisetina Bunge, E. sinica Stapf, and also from E. distachya L., and E. major Host. It contains several alkaloids, but principally (–)-ephedrine and (+)-pseudoephedrine (Reti 1953, Wallis 1967).

The use of a tea prepared from Ephedra nevadensis S. Watson (Mormon tea) for its stimulant effect was noted by Siegel (1976).

Ephedrine, a commonly used sympathomimetic amine that is found in some Ephedra L. species, has long been known to have contact allergenic properties. Its naturally occurring isomer pseudoephedrine appears also to be a contact sensitiser, but in addition has been shown experimentally to exert anti-inflammmatory activity in vitro. Generalised eruptions following oral administration of ephedrine and pseudoephedrine have also occasionally been reported.


Ephedra L.

Ephedras are the natural source of two clinically important isomeric alkaloids, namely (–)-ephedrine and (+)-pseudoephedrine. These compounds differ from one another only in their stereochemistry. Reti (1953) noted that with the exception of E. americana Humb. & Bonpl., all American ephedras are devoid of alkaloids. This would appear now to be an inappropriate statement since at least four other American species (E. gracilis Stapf, E. nevadensis S. Watson, E. triandra Tul., and E. tweediana C. Meyer) are known to yield ephedrine (see below). There is wide variation in alkaloid content and in relative quantities of ephedrine and pseudoephedrine amongst the various species; generally, the roots, berries, and seeds contain no alkaloids (Reti 1953).

[Ephedrine; Pseudoephedrine]

The following species have been reported to contain ephedrine (Reti 1953, Boit 1961, Shah & Shah 1966, Glasby 1975):

Ephedra alata Decne.
Ephedra altissima Desf.
Ephedra americana Humb. & Bonpl.
(syn. Ephedra andina Poeppig & Endl.)
Ephedra distachya L.
(syns Ephedra gerardiana Wall., Ephedra vulgaris Rich.)
Ephedra distachya L. var helvetica Asch. & Graebner
(syn. Ephedra helvetica C. Meyer)
Ephedra equisetina Bunge
Ephedra fragilis Desf.
(syn. Ephedra altissima Willk.)
Ephedra gracilis Stapf
Ephedra major Host
(syns Ephedra nebrodensis Tineo, Ephedra scoparia Lange)
Ephedra major Host ssp procera Markgraf
(syn. Ephedra procera Fischer & C. Meyer)
Ephedra nevadensis S. Watson
Ephedra pachyclada Boiss.
Ephedra sinica Stapf
(syns Ephedra flava F. Porter Smith, Ephedra ma-huang Liu)
Ephedra triandra Tul.
Ephedra tweediana C. Meyer 

Pseudoephedrine has been reported from the following species (Reti 1953, Boit 1961, Tanker & Kilicer 1978):

Ephedra alata Decne.
Ephedra altissima Desf.
Ephedra distachya L.
(syns Ephedra gerardiana Wall., Ephedra vulgaris Rich.)
Ephedra distachya L. var helvetica Asch. & Graebner
(syn. Ephedra helvetica C. Meyer)
Ephedra equisetina Bunge
Ephedra fragilis Desf.
(syn. Ephedra altissima Willk.)
Ephedra gracilis Stapf
Ephedra major Host
(syns Ephedra nebrodensis Tineo, Ephedra scoparia Lange)
Ephedra major Host ssp procera Markgraf
(syn. Ephedra procera Fischer & C. Meyer)
Ephedra pachyclada Boiss.
Ephedra sinica Stapf
(syns Ephedra flava F. Porter Smith, Ephedra ma-huang Liu) 

Other species are considered in the monographs below.

Contact dermatitis from ephedrine may occur soon after the start of applications or as long as two years after first usage. In some cases, a drug eruption accompanies the contact dermatitis (Abramowitz & Noun 1933). These authors reported the case of a woman who became contact sensitive to a spray used on her child. Ephedrine can cause contact dermatitis of the skin of the eyelids from use in ophthalmic preparations. Most cases present dermatitis of the skin around the nose from ephedrine-containing nasal sprays (Scheer 1929, Ramirez & Eller 1930, Ayres & Anderson 1931, Lewis 1944, Spencer 1945, Romaguera & Grimalt 1980). Localised contact sensitivity of the skin of the penis to ephedrine in a patient who used an ephedrine nasal spray - apparently as a result of passive transfer on the fingers - was reported by Hollander (1936).

Stereoisomeric specificity between various ephedrine isomers should be anticipated in cases of contact dermatitis. Epinephrine (also known as adrenaline), a chemically related sympathomimetic amine, can also cause contact dermatitis (Alani & Alani 1976) which can show isomeric specificity (Gibbs 1970).

Audicana et al. (1991) described a 68 year old patient presenting with a mild itchy dermatosis of the trunk and upper limbs, who exhibited contact sensitivity to ephedrine hydrochloride (5% aq.) which he apparently acquired as a result of the oral administration of an anticatarrhal medicine.

Tomb et al. (1991) investigated a bilateral eczematous eruption on the neck, trunk and arms of a 65 year old female who had taken an oral decongestant containing pseudoephedrine hydrochloride (Rhinalair®) 2 days previously. Upon patch testing, she reacted strongly to (–)-ephedrine (0.1–3% pet.), quite strongly to (+)-pseudoephedrine (0.1–3% pet.), and weakly to (–)-phenylephrine (3% pet.). No reaction was observed to (–)-epinephrine (up to 3% pet.). The patient later presented once again with a severe generalised dermatosis, apparently the result of the oral administration of Rinultan®, a proprietary remedy for colds and flu containing phenylpropanolamine hydrochloride. Phenylpropanolamine is also known as norephedrine; this substance may well have been the primary sensitiser.

A similar case of generalised dermatitis in a 64 year old female was reported by Villas Martínez et al. (1993). Their patient had been using proprietary nasal decongestant medicines (Ipecopan Efedrinado®, Senioral®, and Lasa con Codeína®). On patch testing, she reacted to phenylephrine hydrochloride (10% pet.) but not to ephedrine hydrochloride (10% pet.) nor to phenylpropanolamine (1% aq.). However, she developed a generalised eruption when challenged orally with ephedrine (50mg every 8h) or with phenylpropanolamine (50mg every 8h). Ducombs et al. (1986) have also described a patient (76 year old male) who reacted to phenylephrine hydrochloride but not to ephedrine nor epinephrine on patch testing.

(+)-Pseudoephedrine hydrochloride administered orally to children in proprietary cough and cold remedies has been described as a cause of a fixed drug eruption of a nonpigmenting type (Shelley & Shelley 1987). Earlier, Brownstein (1968) also observed stereoisomeric specificity. Because of the structural similarities between pseudoephedrine and betahistine, Dereure & Guilhou (1996) believe that the fixed drug eruptions caused by these two agents may have a common basis.

[Epinephrine (= Adrenaline); Phenylpropanolamine (= Norephedrine); Phenylephrine (= Metaoxedrine)]



Ephedra foliata Boiss. & Kotschy

This species has been reported to yield both (–)-ephedrine (Glasby 1975) and (+)-pseudoephedrine (Khanna et al. 1976). Khanna et al. (1976) also noted that pseudoephedrine could be obtained from tissue cultures of this species. See Ephedra L. above.



Ephedra intermedia Schrenk & C. Meyer

This species has been reported to contain both ephedrine and pseudoephedrine (Reti 1963, Boit 1961, Glasby 1975, Hikino et al. 1980). See Ephedra L. above.

Hikino et al. (1980) investigated this species for anti-inflammatory activity using four assay procedures. They found that (–)-ephedrine exhibited no significant activity whilst (+)-pseudoephedrine exerted a significant, dose-dependent effect sufficient to explain the empirically observed effects of the administration of the crude herbal material. Ephedroxane, a naturally occurring oxazolidine derivative of ephedrine, which also possesses anti-inflammatory activity (Konno et al. 1979), is not present in sufficient quantity in the plant material to account for the activity of the crude drug (Konno et al. 1979, Hikino et al. 1980).


References

  • Abramowitz EW and Noun MH (1933) Ephedrine dermatoses: clinical and experimental study of a personal case, with a review of the literature. British Journal of Dermatology and Syphilis 45(6): 225-237
  • Alani SD and Alani MD (1976) Allergic contact dermatitis and conjunctivitis from epinephrine. Contact Dermatitis 2: 147-150
  • Audicana M, Urrutia I, Echechipia S, Muñoz D and Fernández de Corres L (1991) Sensitization to ephedrine in oral anticatarrhal drugs. Contact Dermatitis 24(3): 223
  • Ayres S and Anderson NP (1931) Dermatitis medicamentosa due to ephedrine. Journal of the American Medical Association 97: 437
  • Boit HG (1961) Ergebnisse der Alkaloid-Chemie bis 1960. Berlin: Akademie-Verlag.
  • Brownstein MH (1968) Fixed eruptions due to an ephedrine isomer. Archives of Dermatology 97: 115-119
  • Dereure O and Guilhou J-J (1996) Nonpigmenting fixed drug eruption: a new case due to betahistine. Dermatology 193(3): 248-250
  • Ducombs G, De Casamayor J, Verin P and Maleville J (1986) Allergic contact dermatitis to phenylephrine. Contact Dermatitis 15(2): 107-108
  • Gibbs RC (1970) Allergic contact dermatitis to epinephrine. Archives of Dermatology 101: 92-94
  • Glasby JS (1975) Encyclopedia of the Alkaloids. Vol. 1 & 2. New York: Plenum Press.
  • Hikino H, Konno C, Takata H, Tamada M (1980) Antiinflammatory principle of Ephedra herbs. Chemical and Pharmaceutical Bulletin 28(10): 2900-2904
  • Hollander L (1936) Dermatitis of the penis caused by ephedrine. Journal of the American Medical Association 106: 706
  • Khanna P, Uddin A and Sogani M (1976) Pseudoephedrine from in vivo and in vitro tissue cultures of Ephedra foliata Boiss. Indian Journal of Pharmacy 38: 140-141. (Chem. Abstr. 86:68392)
  • Konno C, Taguchi T, Tamada M and Hikino H (1979) Ephedroxane, anti-inflammatory principle of Ephedra herbs. Phytochemistry 18: 697-698
  • Lewis GM (1944) Contact-dermatitis-like lesions following intranasal application of ephedrine. Archives of Dermatology and Syphilology 49: 379
  • Mabberley DJ (1987) The Plant-Book. A portable dictionary of the higher plants. Cambridge: Cambridge University Press.
  • Ramirez MA and Eller JJ (1930) The "patch test" in "contact dermatitis" (Dermatitis venenata). Journal of Allergy 1: 489
  • Reti L (1953) Ephedra bases. In: Manske RHF and Holmes HL (Eds) The Alkaloids. Chemistry and physiology. Vol. 3. pp. 339-362. New York: Academic Press.
  • Romaguera C and Grimalt F (1980) Contact dermatitis from ephedrine. Contact Dermatitis 6: 364
  • Scheer M (1929) A case of dermatitis venenata due to ephedrine. Archives of Dermatology and Syphilology 20: 641
  • Shah CS and Shah NS (1966) Pharmacognosy of Ephedra nebrodensis. Indian Journal of Pharmacy 28: 103-105. (Chem. Abstr. 67:120140)
  • Shelley WB, Shelley ED (1987) Nonpigmenting fixed drug eruption as a distinctive reaction pattern: examples caused by sensitivity to pseudoephedrine hydrochloride and tetrahydrozoline. Journal of the American Academy of Dermatology 17(3): 403-407 [doi] [url] [pmid]
  • Siegel RK (1976) Herbal intoxication. Psychoactive effects from herbal cigarettes, tea, and capsules. Journal of the American Medical Association 236(5): 473-476
  • Spencer GA (1945) Hypersensitivity to ephedrine. Report of a case. Archives of Dermatology and Syphilology 51: 48-49
  • Tanker M and Kilicer I (1978) Determination of l-N-methylephedrine along with d-pseudoephedrine in the aerial parts of Ephedra major. Ankara Üniv. Eczacilik Fak. Mecm. 8: 101-113. (Chem. Abstr. 94:61710)
  • Tomb RR, Lepoittevin J-P, Espinassouze F, Heid E and Foussereau J (1991) Systemic contact dermatitis from pseudoephedrine. Contact Dermatitis 24(2): 86-88
  • Villas Martínez F, Joral Badas A, Garmendia Goitia JF and Aguirre I (1993) Generalized dermatitis due to oral ephedrine. Contact Dermatitis 29(4): 215-216
  • Wallis TE (1967) Textbook of Pharmacognosy. 5th edn. London: J & A Churchill Ltd.



Richard J. Schmidt [Valid HTML 4.01!]



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