The drugs of this class are the chemicals, phenolphthalein and other phthaleins, and the vegetable drugs, aloes, frangula, cas-cara, rhubarb, and senna. These depend for their activity upon resinous bodies, known as emodins (trioxymethylanthraquinone), and cathartinic acid, or upon close relatives of these. Tschirch and Heppe report 2.6 per cent. of emodin in frangula, and 0.61 per cent. in cascara; but Stewart reports about 1.5 per cent. in each. In rhubarb there is 1.5, in senna, 1, and in aloes, 0.8 per cent. These principles are rather readily absorbed, so that the crude drugs or their galenic preparations are believed to be more energetic as cathartics than the separated principles. Their action tends to be enhanced by administration with an alkali. In the case of phenolphthalein, it has been shown by Wood that in the presence of acid fermenting intestinal contents there may be no cathartic effect. As a rule, they do not act so well, or may fail to act, in the absence of bile; but usually in such cases they can be made active by the addition of soap or an alkali.

The essential action of these drugs upon the bowel is that of a stimulant to peristalsis (Ascher and Spiro). When they were placed in isolated loops of intestine, Brieger with dogs, and Flemming with rabbits, found no increase of intestinal secretion and no evidence of inflammation. Indeed, when placed in such loops they tend to be absorbed. Magnus found that senna acted in the large intestine only, and it is highly probable that this is the case with the other drugs of the class. Their cathartic effect usually appears in from seven to twelve hours, the stools after an ordinary dose being soft, but not usually liquid. When the muscular action is excessive, cramp or griping results; and a little griping just preceding the time of the stool is very common. It is claimed that resinous bodies are the cause of this, and not the cathartic principles. Though these drugs are mildly irritant, even large doses do not produce inflammation of the intestine; but if they are not carried out, the active principles, because of their absorbability, pass from the intestine into the blood and produce systemic symptoms. Lieb found that cascara stimulates the uterus. One of the author's patients took 1 ounce (30 c.c.) of the fluidextract of cascara, and, besides the diarrhea, had excitement, hallucinations, weakness of the legs, and a mild degree of collapse. Twenty hours later she had completely recovered.

Therapeutics

Beyond all other drugs, the anthracene derivatives are preferred in habitual constipation, especially that of the atonic type. They are not so good in spastic constipation. By long experience it has been found that they do not to any great extent lose their efficiency by repeated use, and in many instances are taken daily, year in and year out, without even the necessity of increasing the dose. It has been noted further that often a small dose taken three times a day will be just as efficient as a much larger total quantity taken in one dose at bedtime. Rhubarb, frangula, cascara, and senna contain tannic acid. When they are used as brisk cathartics, the purgation is frequently succeeded by constipation. This effect has been attributed to the large proportion of tannic acid, but is probably due rather to the thorough emptying of the bowel, which in chronic constipation takes a long time to refill. The urine from rhubarb is yellow from chrysophanic acid, which turns purple on the addition of alkalies. The stools are also yellow. Aloes, but not aloin, in the larger doses is especially prone to produce congestion of the rectum and pelvic organs, and consequently must be used with caution during menstruation and pregnancy or if there are hemorrhoids. Frangula, or buckthorn, in addition to its cathartic principles, contains amygdalin, similar to that of bitter almonds, and some free hydrocyanic acid (Blyth). It is stronger and harsher than cascara, and is employed chiefly by the veterinarians. Senna, in the form of a decoction (senna tea), or chopped up with figs and prunes, is a favorite household remedy. It is prone to gripe.

Preparations And Doses

1. Aloes (Aloe)

Dose, 4 grains (0.25 gm.), tincture of aloes, 10 per cent.; compound tincture of benzoin, 2 per cent.; pills of aloes, each 2 grains (0.13 gm.) with soap; compound rhubarb pills, 11/2 grains (0.1 gm.) in each; compound extract of colocynth, 50 per cent., this extract being used in making compound cathartic pills. It is also an ingredient of Warburg's tincture (see Quinine).

Aloin (aloinum), the active principle, is a mixture of anthracene derivatives. It varies somewhat according to the kind of aloes from which it is extracted, and is named to correspond. For example, barbaloin is from Barbados aloes, socaloin from Socotrine aloes, and nataloin from Natal aloes. The dose is 1/4 grain (0.015 gm.). It is frequently employed alone in pill or tablet triturate, and it enters into the compound laxative pills of the previous Pharmacopoeia, better known as Pil. A.B.S. and I. Their formula is aloin, A grain (0.013 gm.); extract of belladonna, 1/8 grain (0.008 gm.); strychnine, the pure alkaloid, Tin grain (0.0005 gm.); and ipecac, 1/6 grain (0.004 gm.) in each pill.

2. Frangula (Rhamnus frangula), dose, 15 grains (1 gm.), has an official fluidextract.

3. Cascara sagrada (Rhamnus Purshiana), dose, 15 grains (1 gm.); extract, 4 grains (0.25 gm.); fluidextract, 30 minims (2 c.c.); aromatic fluidextract (cascara, glycerin, 25 per cent., licorice, magnesia, saccharin and aromatics), 30 minims (2 c.c.). Magnesia is said to lessen the bitter taste. From the author's observations it seems to lessen the cathartic activity. The fluid-extracts may be given in doses of 10 minims (0.7 c.c.) three times a day, or 1 dram (4 c.c.) at bedtime, with about equal effect. The aromatic fluidextract was designed to lessen the bitter taste and to prevent griping.

4. Rhubarb (rheum), dose, 15 grains (1 gm.); extract, 4 grains (0.25 gm.); fluidextract, 15 minims (1 c.c.); tincture, 20 per cent., 1 dram (4 c.c.); aromatic tincture (rhubarb, 20 per cent., with cinnamon, cloves, and nutmeg), 1/2 dram (2 c.c.); syrup, 10 per cent., 1 dram (4 c.c.); aromatic syrup, 10 per cent. of the aromatic tincture, 2 drams (8 c.c.); compound rhubarb powder or Gregory's powder (rhubarb, 25; magnesium oxide, 65; and ginger, 10), dose, 30 grains (1/2 gm.); compound rhubarb pills (rhubarb, 2 grains (0.13 gm.), and aloes, 1 1/2 grains (0.1 gm.), with myrrh and oil of peppermint), dose, 2 pills. The syrups are favorites for children. Rhubarb and soda mixture (rhubarb, 1.5; ipecac, 0.3; sodium bicarbonate, 3.5; spirit of peppermint, 3.5; glycerin, 35 per cent., and water), 2 drams (8 c.c.), is no longer pharmacopceial.

5. Senna (senna), dose, 1 dram (4 gm.); fluidextract, \ dram (2 c.c.); syrup, 20 per cent., 2 drams (8 c.c.); compound syrup of sarsaparilla (senna, 1.5 per cent., with licorice, sarsa-parilla, and aromatics), 4 drams (15 c.c.); compound infusion or black draught (senna, 6; manna and magnesium sulphate, each, 12; and fennel, 2 per cent.), 2 ounces (60 c.c.); compound licorice powder (senna, 18; licorice root, 23.6; washed sulphur, 8; oil of fennel, 0.4; and sugar, 50), 1 dram (4 gm.). This last is taken stirred up with water. The confection (senna, 10 per cent.; tamarind, cassia fistula, prune, fig, sugar, oil of coriander), 1 dram (4 gm.), is not now official.

Phenolphthalein (dihydroxyphthalophenone) is insoluble in water and soluble in 13 parts of alcohol; dose 2 1/2 grains (0.15 gm.). It has a mild, non-griping, laxative action, mostly by stimulating peristalsis, but also to some extent by preventing absorption. The effect is a soft, rather large stool. In a Moreau's loop Wood found it unabsorbed after two hours and the contents of the loop increased in bulk, but he does not say whether this was due to osmosis or secretion. No phenol is liberated, and doses in dogs equivalent to from 60 to 100 grains in humans have proved non-toxic (Wood). Enormous doses intravenously have proved non-toxic (Abel and Rowntree). Orland reports 30 grains (2 gm.) taken by a child of 3 years without ill effects. According to Rowntree, it is eliminated by the feces, and none usually appears in the urine, except after a hypodermatic dose. But the author has repeatedly found it in the urine, an alkaline urine after small doses by mouth being of a pink color from its presence. Hydrick, 1914, reports albuminuria from one and two grains. (0.06 and 0.12 gm.) in every case in 20 tests, but in the author's extensive clinical use of the drug with frequent urine examinations there has been no albuminuria. In kidney disease a subcutaneous dose of the drug is retarded in its elimination by the urine; this is the "phthalein test" of kidney function. A very mild and useful combination is phenolphthale'in-agar, of which a level teaspoonful weighs about 15 grains (1 gm.) and contains 1/2 grain (0.03 gm.) of phenolphtha-lein. It sometimes produces nausea after a few days' use. Troches of phenolphthalem N. F. each contain 1 grain (0.06 gm.).