DIVISION III.—CERTAIN POISONOUS ANHYDRIDES OF ORGANIC ACIDS.

I.—Santonin.

§ 569. Santonin (C₁₅H₁₈O₃) is a neutral principle extracted from the unexpanded heads of various species of Artemisia (Nat. Ord. Compositæ). The seeds contain, according to Dragendorff, 2·03 to 2·13 per cent. of santonin, and about 2·25 per cent. of volatile oil, with 3 per cent. of fat and resin. Santonin forms brilliant, white, four-sided, flat prisms, in taste feebly bitter. The crystals become yellow through age and exposure to light; they melt at 169°, and are capable of being sublimed; they are scarcely soluble in cold water, but dissolve in 250 parts of boiling water, freely in alkaline water, in 3 parts of boiling alcohol, and in 42 parts of boiling ether. Santonin is the anhydride of santonic acid (C₁₅H₂₀O₄). Santonin unites with alkalies to form santonates. Sodic santonate (C₁₅H₁₉NaO₄ + 3¹⁄₂H₂O) is officinal on the Continent; it forms colourless rhombic crystals, soluble in 3 parts of cold water.

§ 570. Poisoning by Santonin.—Eighteen cases of poisoning, either by santonin or santonin-holding substances, which F. A. Falck has been able to collect, were nearly all occasioned by its use as a remedy for worms. A few were poisonings of children who had swallowed it by accident. With one exception those poisoned were children of from two to twelve years of age; in five the flower heads, and in thirteen santonin itself was taken. Of the eighteen cases, two only died (about 11 per cent.).

§ 571. Fatal Dose.—So small a number of children have died from santonin, that data are not present for fixing the minimum fatal dose. ·12 grm. of santonin killed a boy of five and a half years of age in fifteen hours; a girl, ten years old, died from a quantity of flower heads, equal to ·2 grm. of santonin. The maximum dose for children is from 65 to 194 mgrms. (1 to 3 grains), and twice the quantity for adults.

§ 572. Effects on Animals.—Experiments on animals with santonin have been numerous. It has first an exciting action on the centres of nerves from the second to the seventh pairs, and then follows decrease of excitability. The medulla is later affected. There are tetanic convulsions, and death follows through asphyxia. Artificial respiration lessens the number and activity of the convulsions, and chloroform, chloral hydrate, or ether, also either prevent or shorten the attacks.

§ 573. Effects on Man.—One of the most constant effects of santonin is a peculiar aberration of the colour-sense, first observed by Hufeland in 1806. All things seem yellow, and this may last for twenty-four hours, seldom longer. According to Rose, this apparent yellowness is often preceded by a violet hue over all objects. If the lids are closed while the “yellow sight” is present, the whole field is momentarily violet. De Martiny,[597] in a few cases, found the “yellow sight” intermit and pass into other colours, e.g., after ·3 grm. there was first the yellow perception, then giving the same individual ·6 grm., all objects seemed coloured red, after half an hour orange, and then again yellow. In another patient the effect of the drug was to give “green vision,” and in a third blue.

[597] Gaz. des Hôpit., 1860.

Hufner and Helmholtz explain this curious effect as a direct action on the nervous elements of the retina, causing them to give the perception of violet; they are first excited, then exhausted, and the eye is “violet blind.” On the other hand, it has been suggested that santonin either colours the media of the eye yellow, or that there is an increase in the pigment of the macula lutea. I, however, cannot comprehend how the two last theories will account for the intermittency and the play of colours observed in a few cases. To the affections of vision are also often added hallucinations of taste and smell; there is headache and giddiness, and in fourteen out of thirty of Rose’s observations vomiting occurred. The urinary secretion is increased. In large and fatal doses there are shivering of the body, clonic, and often tetanic convulsions; the consciousness is lost, the skin is cool, but covered with sweat, the pupils dilated, the breathing becomes stertorous, the heart’s action weak and slow, and death occurs in collapse—in the case observed by Grimm in fifteen hours, in one observed by Linstow in forty-eight hours. In those patients who have recovered, there have also been noticed convulsions and loss of consciousness. Sieveking [598] has recorded the case of a child who took ·12 grm. (1·7 grain) santonin; an eruption of nettle rash showed itself, but disappeared within an hour.

[598] Brit. Med. Journ., 1871.

§ 574. Post-mortem Appearances.—The post-mortem appearances are not characteristic.

§ 575. Separation of Santonin from the Contents of the Stomach, &c.—It is specially important to analyse the fæces, for it has been observed that some portion goes unchanged into the intestinal canal. The urine, also, of persons who have taken santonin, possesses some important peculiarities. It becomes of a peculiar yellow-green, the colour appearing soon after the ingestion of the drug, and lasting even sixty hours. The colour may be imitated, and therefore confused with that which is produced by the bile acids; a similar colour is also seen after persons have been taking rhubarb. Alkalies added to urine coloured by santonin or rhubarb strike a red colour. If the urine thus reddened is digested on zinc dust, santonin urine fades, rhubarb urine remains red. Further, if the reddened urine is precipitated by excess of milk of lime or baryta water and filtered, the filtrate from the urine reddened by rhubarb is colourless, in that reddened by santonin the colour remains. Santonin may be isolated by treating substances containing it with warm alkaline water. The water may now be acidified and shaken up with chloroform, which will dissolve out any santonin. On driving off the chloroform, the residue should be again alkalised, dissolved in water, and acidified with hydrochloric acid, and shaken up with chloroform. In this way, by operating several times, it may be obtained very pure. Santonin may be identified by its dissolving in alcoholic potash to a transitory carmine-red, but the best reaction is to dissolve it in concentrated sulphuric acid, to which a very little water has been added, to warm on the water-bath, and then to add a few drops of ferric chloride solution to the warm acid; a ring of a beautiful red colour passing into purple surrounds each drop, and after a little time, on continuing the heat, the purple passes into brown. A distinctive reaction is also the production of “iso-santonin”; this substance is produced by warming santonin on the water-bath with sulphuric acid for a few hours, and then diluting with water; iso-santonin is precipitated, and may be crystallised from boiling alcohol. Iso-santonin melts at 138°; it has the same composition as santonin. It is distinguished from santonin by giving no red colour when treated with sulphuric or phosphoric acids.

II.—Mezereon.

§ 576. The Daphne Mezereum (L.).—Mezereon, an indigenous shrub belonging to the Thymeleaceæ, is rather rare in the wild state, but very frequent in gardens. The flowers are purple and the berries red. Buckheim isolated by means of ether an acrid resin, which was converted by saponifying agents into mezereic acid; the acrid resin is the anhydride of the acid. The resin is presumed to be the active poisonous constituent of the plant, but the subject awaits further investigation. There are a few cases of poisoning on record, and they have been mostly from the berries. Thus, Linné has recorded an instance in which a little girl died after eating twelve berries. The symptoms observed in the recorded cases have been burning in the mouth, gastroenteritis, vomiting, giddiness, narcosis, and convulsions, ending in death. The lethal dose for a horse is about 30 grms. of powdered bark; for a dog, the œsophagus being tied, 12 grms.; but smaller doses of the fresh leaves may be deadly.