Constituents

Alkaloids, up to about 3%, but widely varying; the major alkaloid is (–)-ephedrine (Fig. 16.1), together with many others. These include (+)-pseudoephedrine, norephedrine, norpseudoephedrine, ephedroxane, N-methylephedrine, maokonine, transtorine and the ephedradines A–D. Other components are catechin derivatives, and diterpenes, including ephedrannin A and mahuannin A, have been isolated from other species of Ephedra.

Fig. 16.1

Therapeutic uses and available evidence

Ephedra has been used since ancient times in China for asthma and hay fever, as a bronchodilator, sympathomimetic, CNS and cardiac stimulant. Herbalists also use it to treat enuresis, allergies, narcolepsy and other disorders, and anti-inflammatory activity has been observed in extracts. Ephedrine is used in the form of elixirs and nasal drops, and has an additional use as a heart rate accelerator in the treatment of some types of bradycardia. Pseudoephedrine, the D-isomer of ephedrine produced by chemical synthesis, is usually the compound of choice for isolated alkaloid preparations. Ephedra herb, ephedrine and pseudoephedrine are all the subject of European Pharmacopoeia (Eur. Ph.) monographs. Ephedra herb is used as an anti-allergic agent; this is supported by evidence that it induces immunoglobulin A in Peyer’s patches and blocks complement activation by both the classical and alternative pathways.

Toxicological risks

The herb has been abused as a slimming aid, and an ergogenic aid in sports and athletics, but this is dangerous (Fleming 2008). For example, hypertension and other cardiovascular events, and a case of exacerbation of hepatitis, have been noted with high doses. The absorption of ephedrine and pseudoephedrine is slower after ingestion of the herb than for isolated alkaloid preparations, and the other constituents, the ephedradins, mahuannins and maokonine, are mildly hypotensive; but both the herb and the isolated alkaloids should be avoided by hypertensive patients as well as in cases of thyrotoxicosis, narrow-angle glaucoma and urinary retention. Therapeutic doses of the herb are calculated to deliver up to 30 mg of the alkaloids, calculated as ephedrine.

Toxicological risks

Camphor has been in use for many years; however, ‘camphorated oil’ was recently taken off the market since, in large quantities, camphor may be absorbed through the skin causing systemic toxicity. Overdose causes vomiting, convulsions and palpitations, and can be fatal. However, when used externally in therapeutic doses it is generally well tolerated.

Constituents

The oil contains 1,8-cineole (eucalyptol; see Fig. 16.4) as the major component, with terpineol, α-pinene, p-cymene and small amounts of ledol, aromadendrene and viridoflorol, aldehydes, ketones and alcohols.

Fig. 16.4

Therapeutic uses and available evidence

The oil is antiseptic, antispasmodic, expectorant, stimulant and insect repellent. It is a traditional Australian Aboriginal remedy for coughs, colds and bronchitis. It may be taken internally in small doses (0.05–0.2 ml), as an ingredient of cough mixtures, sweets and pastilles, or as an inhalation; it is applied externally in the form of a liniment, ointment or ‘vapour rub’. The leaf extract and oil have well-defined antiseptic effects against a variety of bacteria and yeasts. The oil is also insect-repellent and larvicidal, and is used in pharmaceutical products for these properties as well as for its antiseptic and flavouring properties in dentifrices and cosmetics. It is widely used in Menthol and Eucalyptus Inhalation BP for steam inhalation as a decongestant. Eucalyptus oil is irritant and, although safe as an inhalation, caution should be exercised when taken internally as fatalities have been reported.

Constituents

Butterbur contains sesquiterpene lactones (eremophinolides), including a series of petasins and isopetasins, neopetasin, petasalbin, furanopetasin, petasinolides A and B, and flavonoids including isoquercetin glycosides. However, toxic pyrrolizidine alkaloids (senecionine, integerrimine, senkirkine, petasitine and neopetasitine) may be present, usually in higher concentrations in the root.

Therapeutic uses and available evidence

Butterbur is traditionally used as a remedy for asthma, colds, headaches and urinary tract disorders. It is used as an antihistamine for seasonal allergic rhinitis, and a recent randomized, double-blind comparative study using 125 patients over 2 weeks of treatment showed that butterbur extract is as potent as cetirizine. The anti-inflammatory activity is due mainly to the petasin content. Extracts inhibit leukotriene synthesis and are spasmolytic, and reduce allergic airway inflammation and AHR by inhibiting the production of the Th2 cytokines IL-4 and IL-5, and RANTES (Brattström et al 2010), thus supporting its use in asthma. Use as prophylactic treatment for migraine has also been suggested but further evidence of efficacy is needed (Agosti et al 2006). The usual dose is an extract equivalent to 5–7 g of herb or root. Internal use is not recommended unless the alkaloids are present in negligible amounts or have been removed from preparations, as is the case with the commercially available product, which is a ‘special extract’. Maximum intake of the alkaloids should be less than 1 μg daily for fewer than 6 weeks per year.

Constituents

Key active principles are furanocoumarins, the most important being khellin (Fig. 16.5), together with visnagin, visnadin and khellol glucoside.

Fig. 16.5

Therapeutic uses and available evidence

Khellin, visnadin and visnagin are vasodilators, with calcium channel blocking and spasmolytic activity. Khellin was the starting material for the development of several important semi-synthetic derivatives such as sodium cromoglycate, which is widely used as a prophylactic treatment for asthma, hay fever and other allergic conditions, often in the form of an inhaler or eyedrops. It was also the basis for the development of nifedipine (a calcium channel antagonist and vasodilator) used in heart disease, and amiodarone, a cardiac antiarrhythmic.

Constituents

All contain the phenolic glycosides salicin (salicyl alcohol glucoside), populin (benzoyl salicin) and a volatile oil containing α-caryophyllene, with cineole, bisabolene and farnesene. Flavonoids (pinocembrin and pinobanksin) and, in P. nigra at least, lignans, based on isolariciresinol, have been isolated.

Therapeutic uses and available evidence

Balm of Gilead is an expectorant, stimulant, antipyretic and analgesic. It is a common ingredient of herbal cough mixtures, and also ointments used for rheumatic and other muscular pains. The phenolic glycosides (e.g. salicin) and the volatile oil constituents have antiseptic and expectorant activity. Little evidence is available for efficacy, but the drug has a long history of traditional use. The bark of poplar species is used in a similar way to willow bark, as an antirheumatic.

Balm of Gilead is generally non-toxic, except for patients who are allergic to salicylates. If excessive amounts of these drugs are taken, adverse effects such as stomach upset and tinnitus are possible, due to the salicylate content.