The dried rhizome and roots of Veratrum viride, American hellebore, (Fam. Liliaceae), a tall coarse herb of wet regions, growing in all parts of North America.

Constituents

There is great confusion about the constituents. Veratrine is a term which has been applied to several distinct alkaloids or mixtures of alkaloids. Wright and Luff, and also Couerbe, applied it to an alkaloid that is also known as veratridine; Merck, Bosetti, Ahrens, and others, to an alkaloid known also as cevadine; the United States Pharmacopoeia applies it to a variable mixture of several alkaloids which are yielded by an entirely different plant. Which of these is employed in pharmacologic investigations has not always been stated in the reports.

Veratrum viride contains cevadine as its chief constituent. It also contains protoveratrine, veratridine, jervine, rubijervine (acrid), pseudo-jervine (inactive), and some irritant resin. Wood says that it contains only traces of protoveratrine.

Veratrum album, an unofficial species that grows in Europe, owes its essential activity to protoveratrine. It contains also jervine, rubijervine, and acrid resin, but not cevadine.

Veratrine, U. S. P., contains cevadine as its essential constituent, and also cevadilline, sabadine, sabadinine, and vera-tridine. It is obtained from the seeds of Asagraea officinalis, or sabadilla (Fam. Liliaceae).

Preparations And Doses

Veratrum, 2 grains (0.13 gm.). Fluidextract, 2 minims (0.13 c.c). Tincture, 10 per cent., 20 minims (1.3 c.c). Collins states that the full therapeutic dose for adults is 30 to 75 minims (2-5 c.c.) of the tincture, and that if given with 1 to 3 glasses of water it does not irritate the stomach.

Veratrine, the official mixture of alkaloids from sabadilla seeds, is assigned the dose of 1/30 grain (0.002 gm.) by the Pharmacopoeia, but it is a drug of too great power and uncertainty for internal use. Pharmacologic Action. - Locally, all veratrum preparations are very irritant, both because of their alkaloids and because of the presence of acrid resin. If the dust is inhaled, it causes violent sneezing and coughing. If a preparation is swallowed insufficiently diluted, it may cause vomiting; or if not vomited, diarrhea and colicky pains.

Cevadine (frequently called veratrine) is more irritant locally than aconitine, but acts like aconitine on the vagus center.

Pilcher and Sollmann state that there is no direct action on the vasomotor centers. It is also a general muscular stimulant, inducing increased irritability and increased power in all kinds of muscle. In experiments with a frog's gastrocnemius, for example, it causes increased quickness and length of contraction, increased lifting and sustaining power, and lessened fatigue. That this is a pure muscular stimulation is shown by its taking place after the end-plates are paralyzed by curare. But there is a peculiar phenomenon in the muscular relaxation, for this is found to take place very slowly indeed, so that quite an interval elapses before the muscle is ready to contract again. It might be thought that this tardy relaxation is due to a loss of muscle elasticity, but this is not the case, and that the muscle is in an active, though diminishing, state of contraction is shown by its ability to sustain weight during the relaxation, and by the continuous production of heat, which indicates that work is being done. This reaction of muscle, which occurs also from other drugs, is known in pharmacology as the "veratrine action." From therapeutic doses this effect on relaxation is not observed, while there is distinct stimulation of striated muscle. Hence, it is evident that cevadine (veratrine) is a muscular stimulant, and not, as at one time taught, a muscular depressant.

Fig. 30.

Fig. 30. - Normal muscle curve.

Fig. 31.

Fig. 31. - Veratrine muscle curve.

Protoveratrine resembles aconitine in its effects upon the circulation, though it is nearly twice as toxic (o.11 mg. per kilo in rabbit, Eden). It is not so irritant locally as cevadine, and the irritation may be followed by local anesthesia. It stimulates strongly the vagus center, and in large doses the vasoconstrictor center and the cardiac muscle, the stimulation being followed by depression of these structures in the same order. Like cevadine, it is a stimulant of muscle, increasing its irritability and the strength and completeness of its contraction; but the relaxation is prompt and not prolonged, as with cevadine, and muscle fatigue sets in early.

Circulation

After therapeutic doses of any of the preparations there is pure slowing of the heart by vagus stimulation and a lowering of arterial pressure, with perhaps slight stimulation of muscle. After toxic doses there are: excessive slowing, with perhaps irregularity or intermittence from vagus stimulation, then quickening and strengthening of the heart from vagus paralysis, with vasoconstriction and raised arterial pressure, then cardiac exhaustion and collapse. Death takes place with asphyxia from paralysis of the respiratory center, which is contributed to by the heart failure.

Toxicology

The poisoning and its treatment are those of aconite, but veratrum is much more likely to be expelled by vomiting, owing to its very irritant local action in the stomach.

Therapeutics

Veratrine has been used externally as a slowly acting anesthetic in muscular pains and neuralgia, especially in facial neuralgia. But its primary irritation prevents it from being a favorite preparation; and as it may be absorbed through the skin, especially when in the form of the oleate, its local use is not without danger.

Veratrum is used to slow a rapid heart, to quiet an overacting one, and to reduce high blood-pressure. In clinical cases Collins has shown its pronounced effect on the rate of the heart and on both diastolic and systolic pressures. Its chief employment has been in eclampsia, a condition in which very large closes of veratrum have been employed, and at times with an astounding but valuable depression of the arterial tension. Starling and Hirst, independently, have made studies of the arterial pressure in pregnant women, and both have found that high pressure means toxemia. In one of Hirst's eclamptic cases the pressure was 320 mm. of mercury. The drug is not an arterial dilator, therefore it might well be accompanied by nitroglycerin; and caution must be employed not to overdo the depression. The author's attention has been called to the occurrence of collapse in a number of eclampsia cases following the administration of veratrum in large doses for two or three days.

Arterial Dilators

The drugs most employed to dilate the arteries are those of the nitrite group, and to a slight extent chloral hydrate and potassium iodide.