Santoninum

Volume II — Main text

Santoninum.-A crystallised neutral principle (C15H1803) obtained from worm-seed . I. Provings.-1 . Dr. EDMUND ROSE one e. took 3 gr., and repeated dose in 3 h. At this time the blue halo of a wax taper appeared yellow. His sleep was disturbed by colic. On awaking his skin seemed to him to have a corpse-like hue, the white bedcover appeared yellow. The urine was of an orange colour. He then took 4 gr., and in course of forenoon 8 gr. more. His mind was somewhat confused, and there was some nausea, which disappeared after a hearty meal. In e., when taking a walk, everything appeared yellow, and men like wandering ghosts. He felt weary also, and vision was not perfectly distinct. Urine was more frequent but less abundant than usual ; it grew red on addition of alkali, but this colour disappeared on addition of nitric acid. Sense of weariness continued more or less for 5 d.; red tint of urine was still apparent after 6 weeks. (Virchow's Archiv, xvi, 237 . Apparently referring to same occasion, Dr. Rose writes (see i, 2), “ I especially remember the unpleasant sensations which I had to endure, after a strong dose, in a perfectly quiet posture, on the covered portions of my extremities, sensations which I cannot describe or compare to anything else. I could not call it formication, for the sensation was a very gentle and continuous one ; neither had it any resemblance to the pricking and numbness in the nerve after pressure on the elbow.") 2. a. One result of the series of experiments which I communicated some years ago* was the manifestation of a series of phenomena of visual illusion in persons poisoned by S. They are reducible to three perfectly distinct classes : 1st. Everyone, however small the quantity taken, was prevented by it from recognising violet light, the spectrum being seen as if curtailed at the violet end, and in mixtures containing violet and yellow the latter predominating (yellow-sight, Gelbsehen). * See Virchow's Archiv, xvi, xviii, xix, xx.

2nd. In a higher degree of intoxication there is impairment of the faculty ofdistinguishing colours; the infinite host ofhues which a healthy person can appreciate being reduced to an extremely small number. The subject is no longer colour-blind (to violet) ; he sees every colour, but certain groups of them make an identical impression. * Both conditions are dependent on the external stimulus of the entrance of light ; but there is a third class of phenomena independent of this, and almost exclusively at least most clearly and beautifully-observed in perfect darkness . The others are illusions ; these are hallucinations . The following experiments were instituted especially to develop the last-named phenomena : b. Dr. H.- took 10 gr., fasting, at 8.38 a.m. At 9.15 the dark field of visiont appeared blue within and bordered with red circle. At 9.24 whole field passed from red through violet to blue. Then green balls made their appearance in it, and specks, partly red and partly yellow, moving very rapidly on the blue ground. This appearance continued of the same kind, and was very intense ; it was not till 10.5 that movement of balls became slower. No large red spot ever appeared on field of vision. At 10.30, no change ; at 11 , a fainter impression . (There was no trace of " violet-sight ; " " yellow-sight," however, did decidedly occur, but abated much at 11.) c. Dr. M- took 15 gr. of santonate of soda, fasting, at 10.29. At 10.36, dark field of vision appeared after some time lilac ; but black objects looked at still appeared black. At 10.47, a dizzy sensation commenced. At II, took colourless bright surfaces for green. Nausea came on, and after food with wine increased to retching (without vomiting), and to dull throbbing pains at chest, worse on stooping. A bitter taste of water, and an indescribable smell, were particularly noticed. (Prover had had a gastric catarrh for 6 months, showing itself by eructations and heartburn .) d. In another, in 25 m. after Oj, dark field after some time appeared blue, with dark blue trailing clouds, which soon disappeared. In another, 30 m. after 10 gr. of santonate of soda, dark field became pure violet, without any movement, disappearing after 3 m. Later, he could not see blue and violet in the spectrum ; and called three discs, dark violet, dark green, and black respectively, all " dark blue.” e. Miss A- took 10 gr. of santonate of soda at 12.10. Had breakfasted as usual, and h. before had eaten a pear. In about 40 m. yellow-sight commenced, with a slight alteration oftaste and smell. After some time whole dark field appeared uniformly pale violet, then red, then bluish, and lastly, dark violet. This remained, and recurred on again closing eyes. On opening them, yellow-sight was strong, and on shaded spots violet-sight was equally marked. f. Same took 6 gr. of santonate of soda, fasting, at 8.23 a.m. No effect for h. At 8.58, on covering eyes, saw bluish-grey streaks on dark field, later a lilac patch. All then vanished ; but a dark yellow was at 9.5 pronounced to be white, and its complementary blue,-a blue gleam also was noticed on Dr. Rose's hand. As yellow-sight was * This Dr. Rose calls , for reasons given, " violet-sight." † I. e., that obtained by closing the eyes.

found very strong at same time (9.8), field of vision was at once darkened ; and after long closing of eyes it looked quite of a reddish violet, without movement, yet with varying intensity. At 9.11, colour of field became fainter, but variation more marked, till at 9.12 colour disappeared entirely, and never appeared any more, though eyes were kept blindfolded till 9.144. At 9.49, yellow-sight and violetsight were clearly present, but no hallucinations.* Miss A- was very nauseated, with retching; relieved by breakfast. At 10.47, flow of water into mouth and a single vomiting, after which a peculiar taste and smell existed, lasting till e., and increasing with return of nausea before supper. Yellow-sight and lilac patches on objects continued slightly till noon . g. Out of 30 human subjects of experiment, there were reportedyellow-sight in all ; violet-sight in 19 ; nausea and vomiting in 14 ; dizzy feelings, lassitude, prostration, in 9 ; hallucinations of vision in 8, of smell in 6, of taste in 5 ; abnormal feelings and pains in the head in 8 ; lowering of the pulse in 2. (Ibid., xxvi.) 3. In 1870 I instituted a series of experiments on myself, and briefly append the result. a. Effect on Vision.-20 m. after 5 gr. I observed flames to assume a decidedly yellow colour, as though spirits were being burnt. Ordinary white glass globes became deeply tinted with yellowish green, and writing-paper exhibited the same phenomenon in somewhat less marked degree. During 3 h. the tints gradually increased, after which they faded by slow stages, and vision was restored to its normal standard. b. Urinary Organs.-5 gr. were taken at bedtime, and next m. an irresistible and almost uncontrollable desire to micturate was felt, the act being attended with some irritation and smarting. The urine was of a deep saffron yellow, staining the pot and linen precisely as bile. It was of sp. gr. 1028. The quantity was decidedly increased, and the urea somewhat in excess. The diuretic action continued during the d.; and it was not till 8 p.m. that the secretion was quite free from foreign pigment. c. Digestive and General Symptoms.- Nausea and dryness oftongue were generally present ; and on one occasion, after a 10 gr. dose, wellmarked tenesmus was experienced both by myself and by a friend who had shared the experiment. After 5 gr., sleep was generally disturbed, and I usually woke unrefreshed, with sickness, frontal headache, and deficient appetite. But the best-marked symptom, and one which I have not hitherto seen described, was a feeling of profound and most unusual depression, accompanied by so much irresolution and want of confidence in my own powers as to render me quite unfit for work of any kind. This invariably followed even a single 5 gr. dose ; and, * Dr. Rose is satisfied that the cause of the yellow-sight is an affection of the retina. The dioptric media are not stained, nor is the optic papilla (ophthalmoscopically) yellow ; on the other hand, in rabbits great hyperæmia ofthe retina under the influence of the drug was plainly made out. The violet-sight he thinks an affection of the conducting apparatus (optic nerves),and the hallucinations one of the centres of vision.

beginning with dulness and heaviness, ran on into very much that sort of melancholia which I imagine jaundice sometimes produces. (FAR- QUHARSON, Brit. Med. Fourn., 1871, ii, 466.) 4. а. Dr. Тн . KRAUSS took at 7 a.m. 2 gr. rubbed up with sugar. Taste slightly bitter. 9 a.m., urine brimstone coloured, acid, on adding NaCO, and heating it became light scarlet. II a.m. , urine with same reaction. 11.30 a.m., suddenly yellow vision came on, objects appeared surrounded by a light yellow border. 3 p.m. , yellow vision returned when he directed his attention to it, otherwise not. 3.30 p.m., yellow vision gone, urine no longer showed above reaction. He now took 2 gr. more. At 4.45 p.m. urine showed above reaction. At 5 p.m., yellow vision, confusion of head, glittering before eyes, frontal headache, pressure on eyes and supra-orbital region, nausea, eructation, rumbling in bowels. On taking a walk all these symptoms went off. Next m., confused head, vertigo, weakness, no yellow vision, urine still showed above reaction, which grew gradually less during d., and was quite gone in e. 7.43 a.m. , 3 gr. At 8.15 a.m. , intense yellow and green vision, but no other symptoms. It declined in h ., and was quite gone in 1 h. Urine showed characteristic reaction. Next m. that had gone. In repeated experiments the yellow vision came 40 to 45 m. after 3 gr. taken, and was gone in 1 h. b. 8 a.m., 6 gr. sant. of soda. Yellow vision came on in 20 m., was very intense, came quite suddenly, lasted hardly I h. Vertigo, slight headache. Urine reacted as above. c. 8 a.m. , 10 gr. sant. of soda. 8.30, intense yellow vision, urine reacted distinctly purple-red like raspberry juice. Urine passed with pain, burning in urethra, constant urging to urinate, but often only a few drops discharged ; the linen was stained deep yellow. Then he had headache, vertigo, pressure in eyes, eructation, nausea, rumbling in bowels, copious discharge of flatus, for about 2 h.; confusion of head and weariness lasted longer. Yellow vision lasted 14 h. d. In order to observe the yellow modification of vision caused by sant. he took 10 gr. sant. that had been exposed to light, rubbed in a mortar, and repeatedly exposed to sun-light. After 2 h. the yellow vision suddenly came on and disappeared in h. Reaction of urine evident, slight gastric symptoms. (Ueber die Wirk. des Santonins, 46.) 5. a. Mr. R- took at 7 a.m. 2 gr. rubbed up with sugar. The urine passed at 2.45 p.m. when mixed with carbonate of soda and warmed, or allowed to stand, showed a scarlet reaction. 7 p.m., it still reacted. No gastric symptoms and no yellow vision. 6. 7.30 a.m., he took 3 gr. sant. of soda. 8.15, yellow vision . Another time at 8 o'clock took 6 gr. of sant. in water. After h. yellow vision, which was gone by 10 a.m. Usual reaction of urine. (Ibid., 48.) c. A boy, æt. 6, who was in the hospital for a broken clavicle, got on Sept. 20th 4 gr. sant. After I h. he passed water like a saturated solution of saffron, the secretion of urine was increased, the colour continued unchanged till the 21st. He then got 6 gr. sant. The urine became still darker, and though he only took 24 pints of fluid he passed 4 pints of urine. The colour disappeared on Sept. 24th, and the

pale yellow urine had an alkaline reaction. (MAUTHNER , Journ. f. Kinderkr., xxii, 1.) 6. On Aug. 30th, a bright clear d., I took 5 gr. h. after luncheon. While engaged in reading some 3 h. after, I became gradually conscious of a yellowish tint on the paper, and fancied there must be a yellow haze in the air. My own hands and the complexion of others appeared of a sallow unhealthy colour, and the evening sky, which was really of a pale lavender tint, seemed to be of a decided light green. Vision was not perfectly distinct for some h., and was accompanied by a certain vagueness of definition. This effect has followed each time a dose of 4 or 5 gr. I felt prostrated and nauseated in the e., was chilly and unable to sit up writing, but after the night's rest all unpleasantness had disappeared. (WALTER S. SMITн, М.В. , Dublin Quarterly Fourn. of Med. Sc., 1. 266.) II . Poisonings.-1 . A little girl, æt. 3 years, was given by her mother, who suspected the presence of worms, some pastilles of santonine, each containing 0.025 milligramme of the drug. One n. and m. producing no effect, she was one e. given 3 at once. A few h. after she awoke complaining of feeling ill generally, and of pains in abdomen. Soon the malaise increased, and she tossed about in bed and complained of general feeling of illness ; she vomited glairy matters. Her features became drawn, and she was so terror-stricken that with cries of alarm she nestled in her mother's arms. Frequent desire to urinate then came on, and with effort small quantities of high-coloured urine were passed. From time to time she had rigors, which made her relations think it was fever. These symptoms lasted 3 h., and then the child rapidly recovered. (E. LABBÉE, Fourn. de Thérapeutique, 1878.) 2. A child, æt. 3 years, took in h. 125 milligrammes of santonine in pastilles. In h. he lost consciousness completely. His head was hot, face swollen and purple. The eyes rolled convulsively in their orbits, the pupils were enormously dilated and insensible to light. The lips were covered with froth and the jaws were tightly locked. Respiration snoring, and convulsive movements of upper extremities. (LOHRMAN, quoted in Ibid.) 3. A child, æt. 4 years, took 12 pastilles of chocolate, in which were 30 centigrammes of santonine. In 2 h. he was very drowsy, with eyes fixed, bloodshot, and insensible to light, lips red and swollen. Respiration jerky and stertorous, pulse 45, soft and small, skin cold and covered with viscid sweat. Incontinence of urine, which passed drop by drop, staining his clothes an orange yellow (turning blood red on addition of nitric acid). This condition lasted 24 h. in spite of treatment, and objects appeared yellow to him during the crisis. (DUCLAUX, in Ibid.) 4. A child, æt. 2 years, was given 2 tablets containing 25 milligrammes of santonine each. In 10 h. slight convulsions in 1. side of face, beginning at angle of mouth and spreading to muscles of orbit, were noticed. Similar clonic convulsions appeared in 1. upper limb. Voice became tremulous and aphonic. Soon these symptoms passed away and he appeared quite well. But in an h. a new crisis appeared,

and whole 1. side was convulsed. Soon convulsions became general and invaded abdominal and respiratory muscles, so that artificial respiration became necessary. Pupils were very dilated, but pulse remained quiet. It took 5 d. for the child to get well, and during that time he had 2 or 3 convulsive attacks a d., less severe, however, than the first. (BINZ, in Ibid. ) 5. A child, æt. 4 years, was given 3 gr. of santonine with her tea. Very soon vomiting set in accompanied by a severe rash, described as urticaria, and covering greater part of body. These symptoms not being referred to the drug a similar dose was given the following n. Almost immediately a white wheal appeared on the nose surrounded by an erythematous blush, and a similar eruption rapidly covered the body. Violent vomiting, without abdominal pain or purging, set in, and the entire face became swollen. In a 4 h. the swelling had increased so as to render the face almost irrecognisable. The lips, from which some viscid saliva issued, were enormously swollen and glistened from oedematous distension, and the eyes were almost closed. The child was put into a hot bath and rapidly recovered. (SIEVEKING, who reports this case, Brit. Med. Fourn. , 166, i, 1871 , says that he never saw so great an exudation ofserum in so short a time.) 6. A girl of 5, in good health, took 6 gr. in divided doses. As soon as she went to bed she was restless, and coughed incessantly all n. At II p.m. vomiting of yellowish slimy mucus set in and continued till next forenoon ; also purging of watery, flaky, foul-smelling stools every 10 or 15 m . Dr. Burdick found the child at this time collapsed, face pinched, extremities rather cold, great restlessness, drawing up of lips over teeth, with pinched expression of mouth and nose ; continual thirst for iced water, which she swallowed greedily. Consciousness clear when awake, but delirium during (restless) sleep. Complains of seeing things yellow ; urine orange coloured. Very restless ; throws her whole body about from one side to another. Abdomen very sensitive, child complaining of dull pain at pit of stomach. In e. abdomen was somewhat tumid, but soft; breathing quick and catching ; tongue deep red, without coating ; perspiration, hot on occiput, clammy on forehead, icy cold on feet, latter creeping steadily upwards. Slight twitchings of facial muscles now set in. At 9 p.m., 1. pulse was gone, r. thready and soft ; consciousness clear. After midnight convulsions like tetanus set in,-head thrown backwards, eyes rolling about, countenance distorted, body sometimes nearly curved, with legs turned back ; in intervals grasping at everything, gnawing of fingers, forcing everything into mouth. After four convulsions she died about 2 a.m. (N. Am. Fourn. of Hom., xiv, 139.) 7. Two gr. were taken by a child, æt. 2. In h. it was seized with convulsions ; and within 1 h. it lay unconscious, with hot head and congested face, eyes twitching convulsively, pupils largely dilated and insensible, mouth foaming, teeth clenched, breathing stertorous, and upper limbs occasionally jerking. On the morrow recovery was complete. (Ann. de Thérapeutique, xxii, 180.) 8. A strong boy, æt. 4, had been troubled for some months with ascarides, for which he had occasionally got 2 gr. of santonine. On VOL. II . 16

November 4th (on recovery from a severe catarrhal attack), the mother gave him for ascarides 2 gr. of sant. at noon, and the same in afternoon. After his dinner he complained of sickness and inclination to vomit, stomachache, pain in abdomen, and at length vomited his food and a quantity of viscid mucus. A stool he then had brought away a quantity of ascarides. After the vomiting the child was very ill, lazy, and sleepy, and complained constantly of bellyache. Thinking it was from ascarides remaining, another dose was given. After h. vomiting and faintness reappeared. The nausea continued, the complexion became pale, blue rings round eyes, he sought staggering a quiet corner on his mother's lap, complained of constant stomachache and griping in bowels. At 6 p.m., the skin of all the body became cold, lips and ears bluish, face snow white, eyes turned up so that only the whites were visible, twitching of hands and feet, breathing hurried, crowing ; when seen by doctor he lay quite stupid on his mother's lap, the arms and legs hung loosely down ; they were quite cold, eyes dull, expressionless, pupils not dilated, but did not react to light, nausea, pain in belly, which was not painful to pressure, but was drawn in, pulse small, 135, face and forehead cool, moist, with cold sweat. He was so apathetic he allowed anything to be done with him. He only desired to drink. He was put to bed with warm bottles in a darkened room, got warm milk to drink, and getting warm he went to sleep in an h. Sleep restless, he started up, tossed about, but in m. was pretty lively, was still pale and poorly, pulse 110, but soft and full. A dose of calomel was given, and next d. the child was well. (SPENGLER, Deutsche Klinik, November 16th, 1850, p. 507. ) 9. A boy, æt. 8, took 1 gr. of sant. at intervals of 3 h. After the 2nd dose he had trembling of limbs, slight convulsive twitching of facial muscles and fingers, inclination to vomit,yellow vision,delirium, quick pulse, urine orange-coloured with a greenish hue. All symptoms gone after 8-10 h. (GRIMM, Schweizer Zeitsch. f. Med. Chir. u. Geburtsh., 1852, 493.) 10. A delicate but healthy child, æt. 5t, got six I gr. doses of sant. at intervals of 3 h. After the 2nd dose at 7 p.m. restlessness, violent convulsions, trembling of whole body. Convulsions with trismus, general sweat, pale face, dilated pupils, quickened pulse and respiration. Abdomen distended and tender to touch, inclination to vomit, loss of consciousness, orange urine discharged involuntarily. This state continued till 3 a.m.; exhausted, quiet. At 8 a.m. still unconscious , lying on back, will not answer. Face pale, eyes sunken, pupils dilated, pulse slow, weak. Two clysters were given, and he died. (Ibid.) 11. A child, æt. 3, healthy and strong, got from its mother in the course of h., 5 santonine lozenges. After h. unwell, vomiting, convulsions, face blue-red, head hot, eyes convulsively distorted, pupils dilated, insensible to light, frothing at mouth, rattling respirations . After 2 h. the symptoms declined. In another h. consciousness returned, the spasm injaws gave way, the child drank water. Slept a little at n., next m. well. (LOHRMANN, Med. Würtemb. Correspondenzb., xxx, 3, 20.)

III. Experiments on animals.-1. a. Frogs become so apathetic after large doses of santonine (over 10 centigrammes), that they remain on their backs when placed there, and after a time spasmodic movements of the trunk and limbs, spontaneous and from contact, occur. b. In warm-blooded animals there is first a period of depression, but this is followed by excitement. The animal begins to tremble, it pricks up its ears and grinds its teeth. Spasms affect one side of its face, the eyes roll in their sockets, the head shakes, the neck stiffens, then the convulsions become general aud invade the limbs and trunk. (BINZ, quoted by Labbée, loc. cit.) 2. Dr. Mann, under direction of Prof. Falk, made a series of experi- ⚫ments on dogs with sant. and natr. sant. His account chiefly refers to the chemical reactions of the medicine in the body. The only points interesting to us are these :-The effects of sant. on the brain and eye are the production of incoherency and chromatopsy. Convulsions usually precede death in poisoning by sant. (Deutsche Klinik, 1860, 27 and 28) .

Volume IV — Appendix

SANTONINUM.

(See vol. ti, p. S36.)

n. 12. A girl, act. 4, was given a ' worm-cake" containing S. After some h. she had shivering, rigors, fever, vomiting, and diarrhoea. On 2nd d. same symptoms ; on 3rd d. a doctor was called. The child presented a jaundiced tint in skin and sclerotics ; T. 39'3' C. ; face and ankles oedematous ; urine red, containing bile and a great quantity of albumen, casts, and red and white corpuscles. When tested for S. this also was found there. Abdomen was tender, liver especially so. The child was exhausted and depressed, with headache, but no other nervous symptom. The following days the jaundice decreased, until the fever began to diminish ; the stools were but slightly tinged with bile. The albuminuria persisted with the jaundice for 12 d., and then the two disappeared together. Recovery was complete. {Deutsch, Mtd. fTecheaschr., Dec. 26th, 1889.)

1. A young woman with pulmonary tuberculosis, believing she had intestinal worms, took one d. 2 lozenges of S., each containing 2| centier. After 3 h. she became aphasic and could only pronounce the single word " mais " (but). This speechlessness did not last more than 2 h. Patient stated afterwards that a kw seconds after taking the lozenges she began to see objects yellow, and soon it became impossible for her to speak or to answer questions, though she under* stood these well. {Gaz. MSd. de Paris, Sept., 1884.)