Cantharidinum

Volume II — Main text

Cantharidin. A crystalline substance contained in cantharis and other blistering beetles (C10H8O4) . Probably a solid volatile oil. 1. Provings.- 1 . a. May 6th, 7.30 a.m., six young men took gr. at 9 a.m. and II a.m. gr. In all the pulse immediately became slower by 4 to 22 beats per m.; the following m. the pulse was still somewhat slower. All complained of great weakness and prostration, vertigo, and trembling of limbs, with weight in muscles of thighs. They * " Dr. Nottingham, of this town (Liverpool), tells me that he made a series of experiments many years ago which distinctlyproved this. He has recently repeated them with like results ."

had frequent desire to urinate and some smarting in urethra ; all had copious perspiration and loss of appetite. Some had stools, two had none, but ineffectual painful urging and tenesmus . Still some prostration the following d. b. One of the provers , B. C-, æt. 23, medical student, took gr. of C. as above. His pulse immediately fell from 63 to 57. He had much urging to urinate from the first, but after the 2nd dose he had a sharp pain in r. kidney, the urine stopped and he had slight smarting in urethra. He felt very ill, his mind became affected, he had vertigo and staggering. At noon he ate with repugnance. The prostration increased, no urine passed, he felt a dull pain throughout his urinary passages, so that he could point out the exact seat of his kidneys, ureters, and bladder. I h. later his prostration was extreme. He was incapable of moving, his complexion had become livid, his eyes lost their brilliancy, all his features were discomposed, his limbs covered with cold sweat, tendency to faint, vomiting of his food. P. 45. Some Malaga wine revived him, but the amelioration was only transient. 1 h. afterwards the prostration returned with increased intensity, also the paleness, the cold sweat, the pulse was only 30 and intermittent, he vomited the wine he had drank 2 h. previously. He got about 9 oz. of rum, which revived and improved him much. Although not accustomed to take alcohol this large quantity of rum seemed to have no intoxicating effect. He slept quietly and next m. only complained of numbness of thighs. He did not recover his appetite for a few d. (GIACOMIMI, loc. cit.) 2. a. ROBIQUET thus describes effects of C.:-The Tooth gr., placed on paper and applied to edge of lower lip, caused in about h. small blisters. A little cerate being applied served only to extend action over larger surface, and both lips were in consequence covered with blisters. One of his pupils, who was watching its crystallization, felt acute pain in conjunctiva, followed by inflammation, accompanied with small phlyctenæ, and loss of sight for several d. b. From his experiments on animals SCHROFF thought that a centigramme would produce no injurious effect on a human being. The results of this dose, however, were so serious as nearly to prove fatal. It is probable that the action of pure C. is 50 times as powerful as that of cantharis . 10 dr. of a freshly made tinct. of cantharis produced erotic sensations. Nothing of the kind was observed as a result of the action of C. Pain in loins was felt in both cases, but more slowly with C.; and although there was violent inflammation of bladder and ureter, no erotic symptom manifested itself. These results rather lead to the presumption that the aphrodisiac properties of the insects reside in a volatile principle and not in the more fixed C. (PEREIRA, op. cit. ) [We have been unable to obtain the original of Schroff's experiments here referred to, but hope to do so in time for the appendix to this volume.-EDs.] II. Experiments on animals.-I . C. produces both albuminuria and hæmaturia. Shortly after its injection kidney appears congested and swollen, and on microscopic examination it is found that the alterations begin first in the glomeruli and convoluted tubules, and gradually extend to the straight tubules. These changes consist in intense congestion,

especially of the glomeruli, with increased tension of blood in the vessels. Then the liquid constituents of the blood pass through she vascular walls, carrying along with them granules and red and white corpuscles . This exudation then passes from the glomerulus along the whole length of the tubules, the epithelium of which next becomes changed, the cells which line them swelling up, multiplying, and becoming modified in form, migration of leucocytes also occurring. In short, we have the signs of inflammation beginning in the glomeruli and passing along the tubules. The inflammation caused by C. begins in the glomeruli and not in the straight tubes, as is often stated. The first thing noticed is extravasation of leucocytes into the glomeruli and an exudation of a fibrinous matrix ; next, following in order, we notice ( 1) the glomeruli and proximate tubules are filled with a granular fluid ; (2) the cells of the capsule become swollen ; (3 ) cells of collecting tubes are affected and become swollen ; (4) cells of whole urinary tubuli become swollen ; (5) in straight collecting tubules cells become multiplied, and are thrown off, so that the lumen becomes full of exuded cells. (BRUNTON, op. cit.) 2. Dr. CANTIERI made numerous experiments with tinct. of C., blistering plaster, and cantharidin, on rabbits, dogs, and frogs, drug being introduced in various modes. His conclusions are as follows : a. C., when introduced into animal organism, produces changes in blood, corrugating and destroying red corpuscles when brought into direct contact with them, corrugating only when reaching them by absorption . b. It diminishes contractile force of heart and blood-vessels, and thus reduces arterial tension ; it increases rapidity of beats of heart and temperature of body, and leads to wasting and general debility-all phenomena indicating existence of a true and special fever. c. It induces hyperæmia and stasis in various organs, or, if directly applied in substantial dosage, true inflammation. Hyperæmia of cerebrum and cord was found ; in former softening was slight, in latter it reached an advanced stage, being greater in dorsal and lumbar enlargements, especially the latter. Hence arose paralysis of posterior limbs, and in frogs loss of reflex activity. d. There was always pronounced hyperæmia of meninges at base ofskull in situation of medulla oblongata, whence probably-in rabbits and dogs-increased frequency of respiration, and great rapidity of circulation with occasional intermittence. e. C. always induces hyperæmia or even true inflammation of the uro-poietic and genital apparatus ; giving rise to degenerative or parenchymatous nephritis, sometimes with albuminuria. It stimulates the sexual organs, and may produce abortion. f. C. administered internally produces, besides the morbid conditions already mentioned, a true gastro-enteritis with extreme redness and ulceration of mucous membrane of stomach, and yellow mucous diarrhæic discharges. Occasionally, even when injected into veins, if it do not produce ulceration, it occasions hyperæmia of gastro-intestinal mucous membrane and frequent diarrhea. ( Lond. Med. Record., 1874, p. 803.)

1. Rabbits were killed by subcutaneous injection of grm. 010 of cantharidin, dissolved in acetic ether. a. One of these, which died in 20 m., had albumen and flakes of fibrin in urine. Epithelial cells and nuclei of inside of capsule were swollen, and some white corpuscles were found between glomeruli and capsule. b. In those dying 1-4 h. after injection, there was intense congestive distension of vessels, and pyramids were blood-red. In glomeruli vascular branch was separated from capsule by a zone of liquid, more or less thick, containing white corpuscles and yellowish granules. Capsular membrane presented sometimes swollen endothelial cells containing some granules, sometimes only nuclei, as if cell walls had been liquefied and destroyed. Epithelial cells of convoluted tubes were filled with yellow granules and liquid. c. After 2 h., inflammation of tubuli recti and collecting tubes appears, attended by modification of form of cells and migration of leucocytes. d. Bladder, after first emission of (considerable quantity of) urine, which happened 15 to 20 m. after poisoning, remained empty. Surface was red ; it contained some drops of cloudy urine, within which were minute leucocytes and large spherical, or long and flat, cells. (CORNIL, Comptes rendus, xc, 537.) 4. Small doses of cantharidin were given to a dog every second or third d. for a month. At each dose diarrhea and vomiting occurred, and urine contained red globules and hyaline casts. Kidneys presented, post mortem, all the lesions which are observed in an acute or sub-acute albuminous nephritis in man. (Fourn. de l'Anatomie de Robin, 1879.)

Volume IV — Appendix

CANTHARIDINUM.

(See vol. ii, p. 18.)

II. I. A farmer, act. 36, suffering from chronic suppurative ostitis of the humerus, received from a charlatan for the supposed gouty

Sins a powder, which he took at one dose, in beer. May afth, 1875. uring the d. he was seized with nausea, vomiting, lumbar pains, and afterwards with colic ; towards e. there was considerable looseness of the bowels, and during the night profuse sweats, with exacerbation of the pains and vesical and rectal tenesmus. Weakness rapidly became extreme, and death occurred early on the m. of the 26th. At the autopsy was found greenish coloration of the abdomen, with postmortem eCchymoses on the back ; upon the cheek and ear of the 1. side were dusky spots as large as a pea, with the consistence of leather to touch and on section. The genital organs were without morbid appearances. The stomach was found dilated by gas, and contained 150 grm. of a greyish-brown, foetid liquid, in which were present small, hard, yellow masses } in the pyloric cavity was bright inflammatory redness ; elsewhere the mucous membrane was unaffected, but the vessels were greatly injected. There was redness and tumefaction of the duodenum and of the neighbouring portion of the jejunum, but no ulceration } vivid injection of the mesenteric vessels. Within the peritoneum was an effusion of a sero-sanguinolent fluid amounting to about 150 grm. The great venous trunks were found filled with dark but liquid blood ; the arteries were empty j kidneys congested ; bladder empty and normal, but the vessels of its neck were engorged with blood. In the pleural cavities there were almost lOO grm. of sanguinolent seroeity, with some cretaceous deposits at the apices. Within the pericardium was a brownish serosity to the amount of 90 grm. The vessels of the brain were filled with a dark-coloured fluid blood } a slight amount of serosity within the two ventricles. The small bodies found in the stomach and on the coats of the vn\fi%X\ive& n««.\«

made up in great part of brilliant scales of a blue colour from .... elytra of a coleopterous insect of the genus Meloe, the species beinz very probably M. proscarabeus* {V'tert.f, gericht. Mtd.y Oct., 1875.)

• As cantharidin is the active element in all these blistering beetles, above poisoalng undei \tt he^dixv^.