Veratrum Viride. U. S.

Verat. Vir. [Green Hellebore, American Hellebore]

"The dried rhizome and roots of Veratrum viride Alton (Fam. Liliaceae), without the presence or admixture of more than 5 per cent. of stems or other foreign matter." U. S.

Big or False Hellebore, Swamp Hellebore, Indian Poke, Itch-weed, Tickle-weed, Bugbane; Veratre vert, Fr.; Grüner Germer, G.; Vedegambre verdo, Sp.

In the several revisions of the U. S. Pharmacopoeia, veratrum has been handled in a vacillating manner. In 1880 and 1890 the drug was restricted to that obtained from V. viride. In 1900 both V. viride and V. album were recognized, this being done for reason of the large importations of Veratrum (V. album. and there being no practical method of distinguishing between these two drugs. The U. S. Pharmacopoeia IX has wisely restricted the definition, in the interest of uniform medicine, to V. viride. This, however, may offer some practical commercial difficulties as it is not always easy to differentiate its substitution by V. album, and certainly it is almost impossible to detect an admixture with the European drug.

That the two species are very closely allied, and the two rhizomes histologically, chemically, and toxicologically very similar is indisputable, but similarity is not identity. The European plant seems to be more actively poisonous than is the American, and has been said by some chemists to contain a larger proportion of the alkaloids. It usually also has a distinctly greater action upon the intestinal tract and it is probable that the proportionate amounts of the alkaloids differ in the two species. The conclusions reached in an elaborate physiological research made by H. C. Wood and H. C. Wood, Jr., for the Committee of Revision of the U. S. VIII was that the drugs can scarcely be distinguished physiologically, but that the European plant is more likely to disturb the intestines and that in the absence of any cogent reason for recognizing V. album, veratrum viride should alone be retained.

The American hellebore, Veratrum viride, known also by the names of Indian poke, poke root, and swamp hellebore, has a perennial, thick, fleshy rhizome, the upper portion of which is tunicated, the lower solid, and beset with numerous whitish roots. The stem is annual, cylindrical, striated, pubescent, and solid, from three to six feet in height, furnished with bright green leaves, and terminating in a panicle of greenish-yellow flowers. The leaves gradually decrease in size as they ascend. The lower are from six inches to a foot long, oval, acuminate, plaited, nerved, and pubescent, and embrace the stem at their base, thus affording it a sheath for a considerable portion of their length. Those on the upper part of the stem, at the origin of the flowering branches, are oblong-lanceolate. The panicle consists of numerous flowers, distributed in racemes with downy peduncles. Each flower is accompanied by a downy, pointed bract, much longer than its pedicel. The perianth consists of six oval acute segments, thickened on the inside at their base, with the three alternate segments longer than the others. The six stamens have recurved filaments and roundish two-lobed anthers. The ovary is ovoid, tri-carpellary; styles three and persistent. Some of the flowers have only the rudiments of pistils. Those on the upper end of the branchlets are barren, those below fruitful. The fruit is a three-lobed capsule, three-celled, and containing flat imbricated seeds. This indigenous species of veratrum inhabits swamps, wet meadows, and the banks of mountain streamlets. It is more abundant northward, but reaches as far south as Georgia. From May to July is the season for flowering. It is doubtful whether the rhizome should be collected in autumn or just before flowering. It should be thoroughly dried and carefully preserved, as otherwise it deteriorates.

Veratrum album L. (V. viride Roehl., but not V. viride Alton.).—The specific difference between this plant, which is a native of Europe and Northern Asia, and V. viride of North America has been questioned by various botanists, but it is now generally acknowledged that the two species are distinct. (See Index Kewensis; also Engler and Prantl.) V. album resembles closely the American species, but is distinguished by its yellowish-white flowers. The rhizome of V. nigrum of Central Europe is said to be sometimes substituted for that of V. album, but is much smaller. According to the Pharmacographia, that of the Mexican species, V. frigidum Schl., exactly resembles that of V. album.

Properties.—As found in commerce, veratrum is usually in small pieces or fragments, but sometimes it comes whole or sliced, so that its characteristic form may be observed. In this condition it is seen to consist of a rhizome one to three inches in length by somewhat less than an inch in thickness where broadest, tapering to a very obtuse or truncated extremity, simple or divided, compact but light, of a dark-brown color externally, and either closely invested with numerous yellow rootlets often several inches long, or exhibiting marks on the surface whence they have been removed. When sliced, the cut surface is of a dingy-white color. The rootlets are from three to six inches long, about as thick as a large knitting needle, or somewhat thicker, obviously much shrunk in drying, and marked by numerous closely set indentations, which give them a characteristic appearance. Not unfrequently portions of the dried stem or leafstalks remain attached to the rhizome, which should always be rejected, as they were ascertained by Procter to be inert. (A.. J. P., 1864, p. 99.)

Veratrum Viride is officially described as follows : "Rhizome upright, obconical, usually cut longitudinally into 2 to 4 pieces, from 2 to 7 cm. in length and from 1.5 to 3 cm. in diameter, externally light brown to dark brown or brownish-black, frequently bearing at the summit numerous, closely arranged, thin leaf-bases, otherwise rough and wrinkled, somewhat annulate from scars of bud-scales and bearing in the outer portion numerous roots, the lower part more or less decayed; fracture hard and horny; internally yellowish or grayish-white, marked with numerous, irregular fibre-vascular bundles; inodorous but sternutatory; taste bitter and acrid. Roots nearly cylindrical, from 3 to 8 cm. in length and from 1 to 3 mm. in diameter; externally light brown to yellowish-brown, deeply transversely wrinkled; fracture short, bark whitish, very thick, enclosing a porous central cylinder. The powder is grayish-brown to dark brown, strongly sternutatory; under the microscope it exhibits numerous starch grains from 0.003 to 0.02 mm. in diameter, spherical or ellipsoidal, single or 2- to 3-compound, the individual grains being often swollen or otherwise more or less altered; calcium oxalate in raphides, from 0.035 to 0.15 mm. in length; fragments with tracheae, the walls being more or less strongly lignified and marked with scalariform or reticulate thickenings, frequently containing a lemon-yellow substance and associated with narrow, slightly lignified, porous, sclerenchymatous fibers; reddish-brown or brownish-black cork fragments occasional." U. S.

It has been asserted that the color of V. album is much lighter than that of V. viride, but this certainly is practically incorrect, however it may apply to carefully preserved specimens. Very commonly the roots have been removed from commercial V. album, while in America they are generally allowed to remain on the rhizomes. According to R. H. Denniston, no microscopic differences can be detected in the rhizomes, but in the roots distinction is possible owing to the fact that directly beneath the epidermis in the V. viride the collenchyma region consists of but two or three rows of large, irregular and distorted cells, while in V. album this region is generally made up of seven to eight rows of rounded, thicker-walled and smaller cells, which are not in the least distorted. Any such test is, of course, inapplicable to the drug in powder. In the color test proposed by R. H. Denniston, sulphuric acid is added to the powder; with V. album a brick-red color, with V. viride an orange-red color, will be produced. Of course the test is of little value in determining the character of a powder, as it does not possess sufficient differentiation.

The pharmacognosy of V. viride has been well illustrated by Bastin (A. J. P., 1895, p. 196). The structure of V. album has been presented by Meyer (Arch. d. Pharm., 1882, p. 81; and in "Wissenschaftliche Drogenkunde," vol. 2, p. 46). Rosenthaler has submitted veratrum to pyroanalysis and has obtained a sublimate which is in part crystalline and gives a yellowish-red color with sulphuric acid. (Apoth. Zeit., xxviii, p. 991.)

(much chemistry deleted - MM)

Uses.—The various alkaloids present in veratrum act upon the system in very different manners, and none of them appears to exercise exactly the same action as the whole drug. According to H. C. Wood (Phila. Medical Times, 1874, iv, p. 737), jervine is a depressant to the respiratory center, to the vasomotor center, and to the heart muscle, and also lowers reflex activity by an effect upon the spinal cord, and rubijervine is chiefly a stimulant to the cardio-inhibitory mechanism, but has a more depressant action upon the respiratory center. According to Eden (A. E. P. P., 1892, xxix, p. 440), small doses of protoveratrine stimulate cardiac inhibition thereby causing a lowering of the blood pressure. In large doses there is a secondary paralysis of inhibition accompanied by rise in the pressure. In large quantities it also exercises a poisonous effect upon the voluntary muscles similar to that of veratrine. Rubijervine is present in such small proportions (according to Breideman, J. P., 1906, lxxxiv, 0.053 per cent.) and is so feeble a substance that it is improbable that it plays any part in the physiological action of the drug. Jervine, although present in larger quantities (0.34 per cent.), according to H. C. Wood, Jr., is less poisonous than the drug itself. Protoveratrine, although present in small amounts (0.06 per cent., according to Breideman), is an extremely toxic substance and is the most important of the ingredients at present known. It appears to differ, however, in some of its properties from the whole drug.

When a moderate dose of veratrum is introduced into the system, the most marked change produced is reduction in the rate of the pulse accompanied with a fall in the arterial pressure. At the same time there may be some slowing in the respiration. With proper doses the slowing of the pulse is extreme and we have seen, in the lower animals, even complete arrest of the heart at this stage of the poisoning. The slowing of the pulse does not occur if the pneumogastric nerves have been divided previous to the injection of the drug, and is at once abolished either by section of these nerve's or by the administration of atropine. It must be regarded, therefore, as due to stimulation of the cardio-inhibitory center. The reduction in the arterial tension in the normal animal may, therefore, be attributed to the slowing of the pulse. The conclusions of H. C. Wood, Jr. (U. P. M. B., March, 1908), that contrary to the older views, veratrum does not lower arterial tone, have been confirmed by the experiments of Pilcher and Sollmann (J. P. Ex. T., 1915, vii, p. 295) on animals and the observations of Collins (A. I. M., 1915, xvi, pp. 54-58) on man. After toxic doses of veratrum there is a late paralysis of the intracardiac terminals of the pneumogastric nerve and consequent increase in the pulse rate with at first a rise of the blood pressure followed by a fall. This toxic fall in the blood pressure appears to be due to a direct depressant action upon the heart muscle. There is, following the toxic dose, also marked reduction in the respiratory activity, death being due eventually to failure of this function.

Veratrum was introduced into medicine about a century ago by the group of physicians who called themselves "eclectics." By them it was attributed with mysterious "adenagic" virtues and used in all sorts of inflammatory diseases. Later under the belief that it dilated the blood vessels and hence would relieve various local congestions, regular practitioners employed it largely in the treatment of pneumonia, peritonitis, and other sthenic fevers. While it is still employed to some extent in this type of disorder, our knowledge of its physiological action indicates that its true field of usefulness is rather in chronic, than in acute, diseases. Thus it is a very valuable agent for the reduction of excessively high blood pressure in arteriosclerosis, interstitial nephritis, and other conditions of hypertension; in cases with feeble myocardia it should be used cautiously because the stimulation of the cardio-inhibitory mechanism predisposes to cardiac dilatation. For the same purpose it is often employed in threatened apoplexy, in chronic endocarditis, especially in those in which there is considerable degree of cardiac hypertrophy, and in the so-called irritable heart seen in soldiers and athletes. In exophthalmic goitre and various other forms of tachycardia it is frequently of great service to reduce the pulse rate and prevent the heart exhausting itself in excessive activity. In certain of these conditions its line of usefulness more or less parallels that of digitalis. It differs, however, sharply from that drug, in that while digitalis tends to increase the tone of the heart muscle, veratrum rather diminishes cardiac tone. Veratrum has also been used widely by obstetricians in the treatment of puerperal eclampsia. Whether its benefit in this condition is to be attributed to a depressant action upon the motor cord, as some believe, or whether it be due to a lowering of the blood pressure, is as yet uncertain. The dose of veratrum must be gauged by the effect it produces; in general it may be said that if it does not slow the pulse no benefit will be received by the patient. The drug should therefore be pushed until evidence of its action is seen in the reduction of the pulse rate. Ordinarily from one to three minims (0.06-0.2 mil) of the fluidextract may be given every two or three hours until it manifests its action. It should be remembered, however, that in some cases the cardio-inhibitory mechanism is refractory to the action of the drug and no dose will slow the pulse, and if given incautiously it may do great harm. Fortunately in most instances if given in too large dose it will manifest its toxic action by nausea before any more serious symptoms are produced.

Toxicology.—The symptoms of veratrum poisoning are vomiting accompanied with great nausea and much retching. There is profound prostration with muscular weakness, the skin bedewed with perspiration and pale in color, the pulse, in the milder cases, or in the early stage of the severe cases, is extremely slow and easily compressible, later, in the severe types of poisoning, it may become rapid and irregular. The respirations are often shallow and sometimes stertorous. Frequently there is much complaint of dizziness and in a few cases there has been dilatation of the pupil with disturbance of vision. Because of the promptness with which vomiting comes on even very large single doses of veratrum may be recovered from, thus Buckingham (A. J. M. S., 1865) reports a case in which recovery followed a teaspoonful of the fluidextract. But when repeated large doses have been taken, the poisoning is much more dangerous.

In the treatment of veratrum poisoning if the patient be vomiting it is well to give a couple of glasses of water in order to thoroughly cleanse the stomach, at the same time twenty grains (1.3 Gm.) of tannic acid may be exhibited as an imperfect chemical antidote. If for any reason vomiting has not occurred it should be at once provoked or the stomach washed out by means of a stomach pump. The patient must be kept in a horizontal position and should not be allowed to sit up to vomit. After washing out the stomach in the manner described above, efforts should be made to stop the vomiting by the use of counter-irritation over the epigastrium and the cautious employment of morphine. But since when the drug proves fatal death is due to the respiratory arrest the latter should not be given in too large doses. If seen in the early stages when the pulse is slow, atropine is a remedy of great value antagonizing the effect of the veratrum upon the pneumogastric nerve and at the same time checking the excessive sweating and stimulating the respiratory center. Other active respiratory stimulants, such as hypodermic injections of ammonia and strychnine, may be employed, and if the bodily temperature is low it should be maintained by the external application of heat.

Dose, one to two grains (0.065-0.13 Gm.).

Off. Prep.—Fluidextractum Veratri Viridis, U. S.; Tinctura Veratri Viridis, U. S.

The Dispensatory of the United States of America, 1918, was edited by Joseph P. Remington, Horatio C. Wood and others.