There are some other drugs with effects of the digitalis kind, and the whole group is known as the digitalis group, or the digitalis series. The members of the group that are employed as circulatory stimulants are digitalis, strophanthus, squill, convallaria, apocynum, adonis, and their active principles, and the glucosides, ouabain and helleborein. Several other drugs, such as oleander, cereus grandiflorus, and erythro-phleum (sassy bark), are reputed to have some of the actions of digitalis, but have not come into general use.

Strophanthus (strophanthus), "the ripe seed of Strophanthus Kombe or of S. hispidus (Fam. A pocynaceae), deprived of its long awn," comes from a woody climbing plant of eastern Africa.

Constituents

The seeds contain from 1 to 3 per cent. of an active body, strophanthin. This is either a single glucoside (methyl-ouabain) or a mixture of glucosides, and is souble in water and alcohol. Strophanthus is relatively much more toxic to the heart muscle than digitalis, as shown below.

Preparations And Doses

Strophanthus, 1 grain (0.06 gm.). Tincture, 10 per cent., 10 minims (0.6 c.c). Strophanthin, 1/120 grain (0.0005 gm.). The U. S. P. requires a biologic assay.

Convallaria (not official) is "the dried rhizome and roots of Convallaria majalis (Fam. Liliaceae)," the common lily-of-the-valley, which grows wild in Europe, Asia, and the Allegheny Mountains. The drug contains the active glucoside, conval-lamarin, and a saponin-like glucoside of the digitonin type, convallarin. The fluidextract is employed, dose, 10 minims (0.6 c.c.). Convallaria is relatively much more poisonous than digitalis, as shown below.

Squill (scilla), dose 1 1/2 grains (0.1 gm.), contains the glucosides, scillain and scillitoxin, bodies of uncertain composition. It has for preparations the fluidextract, the 10 per cent. tincture, the 10 per cent. vinegar (aceturn), and the three expectorant mixtures, syrup of squill, which contains 45 per cent. of the vinegar, the compound syrup of squill, which contains 8 per cent. of the fluidextract, and the National Formulary preparation, mistura pectoralis (Stokes' expectorant), which contains 3.5 per cent. of the fluidextract. The expectorant effect is probably the result of a nauseant action in the stomach. The U. S. P. requires a biologic assay.

Apocynum (dogbane), dose, 15 grains (1 c.c.), is used in the form of the fluidextract. It contains a non-glucosidal body, cymarin, which is used in dose of 1/200 grain (0.0003 gm), and the glucosides, apocynin and apocynein.

Adonis vernalis is not official. Its dose is 10 grains (0.6 gm.), and it is employed in the form of fluidextract or infusion. Its active glucoside, adonidin, may also be used in dose of 1/10 grain (0.006 gm.).

Ouabain, known as "crystalline gratus strophanthin," is a stable crystalline glucoside of great activity. Its lethal dose is that of strophanthin. Because of its stability it has been suggested as a standard for physiologic comparison. It is employed intravenously.

The Standardization And Permanency Of Preparations

Edmunds, by physiologic assay of 16 different commercial samples of the tincture of digitalis, found that the dose necessary to produce systolic standstill in a 20 gm. frog varied from 0.08 c.c. of the strongest to 0.29 c.c. of the weakest. A tincture made from one batch of drug might thus have three or four times the strength of one made from another batch of drug, and the correct dose of one would be the wrong dose of the other. Haynes, Hale, and others have found similar variation. In addition, all the preparations slowly deteriorate on keeping. It is because of these things that the Pharmacopoeia has adopted the biologic assay, by the "one-hour-frog" method. Unfortunately, this method is not of use for the comparison of different drugs, but only for comparison of different preparations of one drug.

Houghton's table of comparisons of the minimum fatal dose of official preparations, as tested by the frog method, is as follows:

Digitalis....................

Fluidextract................

0.0015 c.c.

Tincture...................

0.015 c.c.

Extract .........................................

0.0005 gm.

Strophanthus...............

Tincture...................

0.000083 c.c.

Convallaria.................

Fluidextract................

0.00025 c.c.

Squill.......................

Fluidextract................

0.0012 c.c.

This would make the relative toxicity of equal amounts of the drug as follows: digitalis, 1: strophanthus, 18.5; convallaria, 6; squill, 1.2. Hatcher's figures from equal amounts by intravenous dosage in the dog are: digitalis, 1; convallaria, 1/5; apocynum, 1/7; squill, 1/57. These figures do not show the relative clinical efficiency, however, but only their relative toxicity; and the clinical doses bear no relation to the lethal doses. In proportion to the therapeutic dose, except by intravenous administration, digitalis is the least toxic of them all.

Worth Hale's comparison of active principles by the frog method is as follows: The minimum fatal dose of strophanthin is 0.0000011; of convallamarin, 0.00000475; of digitoxin, 0.0000085; of French digitalin, 0.000013; of digitalein, 0.000024; of German digitalin, 0.00007. This would make the relative toxicity of equal amounts as follows: digitoxin, 1; strophanthin, 8; convallamarin, 2; French digitalin, 2/3; digitalein, 1/3; 11

German digitalin, 1/8 approximately. Hatcher's comparison of toxicities in cats by intravenous administration is: ouabain, 4; digitoxin, 1; scillitoxin, 1; true digitalin, 1/4; convallamarin, 1/4; digitalein, 1/9; German digitalin, 1/9.

As to the reliability of preparations of strophantus we have some evidence. Hatcher tested old and new tinctures of strophantus, and tinctures made from recently imported seeds and from very old seeds, and reported them as being fairly uniform. He claims that, unlike digitalis, strophanthus does not deteriorate with age. Houghton reported that the tinctures of strophanthus on the market varied so that the strongest were three times as strong as the weakest; and Edmunds, in testing five specimens of the tincture by their power to bring a 20 gm. frog's heart to systolic standstill, found the strongest four times as strong as the weakest. (It took 0.0012 c.c. of the strongest and 0.005 c.c. of the- weakest.) So the possibility of great difference in the strengths of preparations must be borne in mind, and reliable assays taken advantage of when possible. Houghton has also reported that he has found wide variation in the activity of commercial strophanthins, one sample being 90 times as fatal as another.