The belladonna group includes belladonna (deadly nightshade), stramonium (jimson-weed or thornapple), and hyoscya-mus (henbane), all of which belong to the potato family, the Solanaceae, and have similar constituents and related pharmacologic actions.

Occurrence

Belladonna (Atropa belladonna) is a purple-flowered herb of central and southern Europe and western Asia. It is cultivated for the market in England and Germany. Stramonium (Datura stramonium), also known as thornapple and jimson-weed, is a tall, coarse, narcotic smelling herb, which fruits with a spiny, four-valved capsule the size of a walnut, filled with small black seeds. It grows in Asia, Europe, and the United States east of the Mississippi, and may be found in abundance in the vacant lots of our eastern cities. Poisoning from the swallowing of the seeds by children has frequently been reported. Hyoscyamus (Hyoscyamus niger) is an herb native to Europe and more or less cultivated.

Constituents

The active principles are alkaloids, the chief of which are atropine, hyoscyamine, and hyoscine. Atropine is a compound of equal amounts of the isomers, dextro- and levo-hyoscyamine, into which it separates when dissolved in water. Hyoscyamine is levo-hyoscyamine, and is readily changed to dextro-hyoscyamine. In the growing belladonna the hyoscyamine is said to form in the young leaves, to be later changed to atropine.

According to the predominance of one or other of these alkaloids, and to the amounts present, the drugs of this group fall into a regular pharmacologic series, as follows:

1. Belladonna (root and leaves) - the leaves contain 0.35 per cent., and the root, 0.5 per cent., of alkaloid, which is nearly all atropine. It has, therefore, a typical atropine action.

Fig. 46.

Fig. 46. - Datura stramonium, Linne - flowering branch (Maisch).

Fig. 47.

Fig. 47. - Capsule of stramonium (Bastin). The seeds have frequently been the cause of poisoning.

2. Stramonium (leaves) contains 0.35 per cent. of alkaloid, mostly hyoscyamine, but with small amounts of atropine and hyoscine. It is less stimulating to the cerebrum and may be narcotic.

3. Hyoscyamus (leaves) contains (0.065 per cent. of alkaloid, mostly hyoscyamine, with a fair amount of hyoscine, and only traces of atropine. It is rather narcotic, but is weaker than the other drugs of the group.

Preparations And Doses

The dose of belladonna, or stramonium is 1 grain (0.06 gm.); that of hyoscyamus, 4 grains (0.25 gm.). The doses of the preparations can readily be estimated from their known strengths. The official preparations are:

The fluidextracts and extracts of belladonna (fluidextract of root, extract of leaves) and of hyoscyamus, and the extract of stramonium. The 10 per cent. tinctures of belladonna leaves, of stramonium, and of hyoscyamus. In addition:

Of belladonna, the liniment is made by adding 5 per cent, of camphor to the fluidextract; and preparations of the extract are: the ointment, 10 per cent.; the plaster, 30 per cent.; and the unofficial rhinitis tablets, which have various formulae. The formula given to the author by Dr. R. P.

Lincoln, the originator of rhinitis tablets, is: extract of belladonna, gr. 1/8 (0.007 gm.), camphor, gr. 1/4 (0.015 gm.), and quinine bisulphate, gr. 1/2 (0.03 gm.). Another formula is: camphor and quinine sulphate or bisulphate, of each,

1/2 grain (0.03 gm.), and fluidextract of belladonna, J minim

(0.015 c.c.). They are often prescribed "half strength."

Of stramonium, the ointment contains 10 per cent. of extract.

Of the alkaloids, the dose is 1/150 grain (0.0004 gm.), the maximum beginning dose being 1/50 grain (0.0012 gm.). The official salts are: atropine sulphate, hyoscyamine hydrobromide, hyoscyamine sulphate, and scopolamine hydrobromide (hyoscine hydrobromide), all readily soluble in water and alcohol. Atropine can withstand the heat of boiling water without decomposition.

Hyoscine and scopolamine are chemically identical, and in spite of claims to the contrary, are considered by pharmacologists to be physiologically identical.

Pharmacologic Action Of Atropine

The primary actions of the group are those of atropine. They are - (a) To stimulate nerve-centers, and (b) to depress nerve-endings.

(a) The nerve-centers which atropine primarily stimulates are the cerebral and the vital medullary centers. Only in highly poisonous doses does it depress these.

(b) The nerve-endings which atropine primarily depresses are:

1. The sensory nerve-endings - not a marked effect, but tending to lessen sensation and pain. Short and Salisbury (1910) could not detect any cutaneous anesthesia.

2. The motor nerve-endings in the smooth muscle of the viscera (not in striated muscle and arterial muscle) - a strong effect, tending to allay abnormal contraction of the muscles of the viscera (bronchi, stomach, intestines, bile-ducts, etc.).

3. The secretory nerve-endings - a very strong effect, tending to check the mucous, digestive, and skin secretions.

4. The ends of the third nerve in the eye - a strong effect.

5. The vagus nerve-endings - so that the heart is freed from the usual inhibitory vagus control - an effect that is striking but short-lived.

Atropine depresses primarily these nerve-endings, whether it is applied locally or given internally, while it has no effect at all upon most protoplasmic structures. It is, therefore, a highly selective drug. In speaking thus of nerve-endings from a practical point of view, it should be noted that atropine acts on muscle after nerve degeneration, though not on the contractile substance of the muscle; hence it probably affects some material which acts as the receptor of the nerve impulse. It is some part of the neuromuscular junction, though we speak of it crudely as the nerve-ending.

Absorption And Local Action

There is slight absorption from plasters, and fair absorption from oily and alcoholic preparations, as ointments and liniments; so the drug may have an effect through the skin on sensory and secretory nerve-endings. In tests with 66 belladonna and scopola plasters Bastedo and Martin (1901) found that these had distinctly more power to stop pain than had the simple plaster without belladonna. That there is some absorption from the plasters is shown further by the occasional occurrence of poisoning from them. (See Fig. 51.) Absorption is ready through mucous membranes, the drug rapidly disappearing from stomach and duodenum.