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Cantharis (U. S. P.)—Cantharides.

Preparations: Vinegar of Cantharides - Cantharides Cerate - Cantharides Paper - Cantharidal Pitch Plaster - Ointment of Cantharides - Cantharides Liniment - Tincture of Cantharides - Blistering Liquid

"Cantharis vesicatoria, DeGeer"—(U. S. P). (Lytta vesicatoria, Fabricius; Meloë vesicatorius, Linné).
Class: Insecta. Order. Coleoptera.
COMMON NAME AND SYNONYM: Spanish flies, Muscae Hispanicae.

Source, History, and Description.—There are a number of insects inhabiting various sections of the world which possess acrid properties, and which, when applied to the skin, produce vesication; the most common in use are those under present consideration, Spanish flies, or cantharides, the Cantharis vesicatoria of Latrielle, Meloë vesicatorius of Linnaeus, or Lytta vesicatoria and Cantharis officinalis of other naturalists. At what period they were introduced into the practice of medicine is a matter of uncertainty. The beetle, called Spanish fly, is a native of Europe, where it is collected principally in south Russia and Hungary; also in Italy and Spain. It is imported into this country from Messina and St. Petersburg. Those from Russia are the best, and may be known by being larger than the French or English varieties and more copper-colored.

General Characters.—Antennae elongate, simple, filiform; maxillary palpi with terminal joint somewhat ovate; head large, heart-shaped; thorax small, rather quadrate, narrower than the elytra, which are as long as the abdomen, soft, linear, the apex slightly gaping; wings 2, ample (J. F. Stephens). Cantharis vesicatoria, De Geer, the Spanish fly, is of an elongated, almost cylindrical form, from 6 to 11 lines in length, and 1 or 2 lines in breadth. This insect may be distinguished from other analogous ones, by presenting 2 shining-green wing covers, which cover 2 membranous wings, ample, thin, veined, transparent, pale-brown; black, jointed antennae, and a longitudinal furrow along the head and chest. Their smell is strong, virose, very disagreeable, and compared to that of mice; their taste is acrid, burning, and urinous (Ed.). It is of a grass or copper-green color, with numerous whitish-gray hairs on its body and thorax. The head is large, sub-cordate, the eyes lateral and dark-brown; the thorax not larger than the head and narrowed at the base; the elytra or wing-covers are from 4 to 6 lines long, and from 3/4 to 1 1/2 line broad; the costa are slightly margined; the wings 2, with tips folded; the legs are stout, from 4 to 6 lines long, the hinder ones longest. The abdomen is soft, and broadest in the female. In the female, near the anus, are 2 articulated caudal appendages (P.). The U. S. P. thus describes cantharis: "About 25 Mm. (1 inch) long and 6 Mm. (1/4 inch) broad; flattish-cylindrical, with filiform antennae, black in the upper part, and with long wing cases and ample, membranous, transparent, brownish wings; elsewhere of a shining, coppery-green color. The powder is grayish-brown, and contains green, shining particles. Odor strong and disagreeable; taste slight, afterwards acrid. Cantharides should be thoroughly dried at a temperature not exceeding 40° C. (104° F.), and kept in well-closed vessels."

The Spanish fly inhabits the earth in the form of a larva, and comes forth in the state of a fly in the month of May. It infests various trees, as the elder, rose, plum, willow, poplar, and elm, but more especially the privet, lilac, ash, and honeysuckle. They are caught during the month of May, either early in the morning or late at night, when the cold renders them less active; to undertake their removal in the daytime would be a serious measure. Those who gather them cover their faces and guard their hands with gloves, then shake them from the bushes over sheets, and kill them immediately by immersion in vinegar, or by exposure to the vapor of vinegar, spirit, or oil of turpentine. Hager recommends the use of carbon disulphide for this purpose; 7 Cm. to each liter of cantharides in bulk. Thus they are left in a closed vessel for one day. They are then quickly dried in the sun, or with artificial heat which, as stated above, should never rise above 40° C. (104° F.). They are best dried by placing them over caustic lime at a temperature of from 25° to 30° C. (77° to 96° F.).

In the dried state the flies may be known by the preceding descriptions as to color, form, odor, and taste; they are easily reduced to a dirty, grayish-brown powder, dotted with numerous brilliant green points. These points consist of the elytra, head, etc., and do not readily decompose, even when mixed with decaying animal matters. Orfila has recognized. these particles in a body nine months after interment. The vesicating property of the flies may be preserved for many years, if they are kept from moisture in well-stoppered bottles, powdering them only as required. If purchased in powder they may have lost their activity, or suffered from adulteration with euphorbium, capsicum, or with some other insects. To preserve them from insects, various means have been advised, as the introduction of a few lumps of camphor into the vessel containing them, or the addition of carbonate of ammonium, or a few drops of strong acetic acid. Chloroform vapor is said to excel them all. Exposing them for 1/2 hour in glass bottles, to the heat of boiling water, destroys the insects and eggs, without impairing the virtues of the flies; of course they must not be allowed to come in contact with the water. The properties of the fly are much diminished by the insects which feed upon them.

Chemical Composition.—Cantharides powder yields its active properties to boiling water, acetic acid, alcohol, proof-spirit, ether, the fixed and volatile oils. The active principle is a white, crystalline substance termed cantharidin. It is in small, white, pearly prisms, or scaly crystals, which are neutral, practically insoluble in water and cold alcohol, but soluble in ether, benzol, chloroform, acetone (E. Dietrich), alkaline solutions, acetic acid, acetic ether, the oils, wood alcohol, and in boiling alcohol, which deposits it upon cooling, and is insoluble in carbon disulphide; it fuses at 98.8° C. (210° F.), volatilizes at a higher heat without decomposition, and evaporates slowly at ordinary temperatures. It is said to exist principally in the trunk and soft parts of the body, and may be obtained by exhausting powdered cantharides with cold rectified spirit by percolation, concentrating the tincture till most of the alcohol is expelled, and allowing the residue to rest for a long time until crystals form. It may be freed from impurities by elutriation with a little cold rectified spirit, which scarcely acts on crystallized cantharidin; and it may be obtained quite pure by redissolving them in boiling rectified spirit, adding animal charcoal, and recrystallizing them by rest and cooling. Ether is, however, preferred to alcohol in preparing these crystals, as it dissolves less of the green oil, which is very difficult to separate. E. Dietrich (in 1880), has obtained cantharidin in brilliant white crystals by dialysis. The yield was above 0.28 per cent. The composition of cantharidin is represented by C10H12O4, or according to Krafft (1877), C20H24O8. It may likewise be prepared by macerating, at three consecutive times, very finely bruised cantharides, for 24 hours, in a sufficient quantity of chloroform, and then removing this by distillation. The green, thick residue is then treated by carbon disulphide, which dissolves the fatty matter. Throw the whole on a filter, which retains the crystallized cantharidin, which may be purified by several solutions in chloroform (W. Procter, A. Fumouze, M. Mortreux). Baudin (Am. Jour. Pharm., 1889), found 1 per cent total cantharidin, of which 0.72 per cent is abstracted by pure chloroform and 0.3 per cent by chloroform acidulated with 2 per cent of hydrochloric acid. M. Fumouze does not consider cantharidin to be the active vesicating principle of the flies; some cantharides 8 or 10 years old, from which he could obtain no appreciable amount of cantharidin, nevertheless, produced prompt vesication when applied to the skin.

Cantharides contain, besides cantharidin, a green oil, soluble in alcohol, black matter, soluble in water, insoluble in alcohol; a fatty matter, insoluble in alcohol, a yellow viscid substance soluble in water and alcohol, yellow matter soluble in ether and alcohol, free acetic and uric acids, phosphates of calcium and magnesium, etc. (P.). Formic acid is said to be present also (E. Dietrich, 1883). This acid is the best solvent for cantharidin, and this fact may explain why decoctions and alcoholic preparations of cantharides are active, as cantharidin, which is generally believed (against Fumouze) to be the vesicating agent, is practically undissolved by water or by cold alcohol. Others explain the solvency of cantharidin in decoction and tincture as being due to its being combined in the beetle, with the yellow matter, which is dissolved by both alcohol and water. The best menstruum (for ordinary use), for cantharides, is chloroform, or ether, which dissolves only the active constituents. Cantharides, in powder or tincture, is sometimes used criminally for aphrodisiac purposes, and is administered to the female victim in coffee, chocolate, brandy-punch. wine, porter, ale, etc. If any particle of the flies is present, the microscope will detect it; otherwise, the only resource left is to ascertain whether cantharidin is present in the suspected liquid. The best test in such a case is to demonstrate its vesicating power. According to C. R. C. Tichborne, Esq., this may be accomplished by the following process: To 1/2 pint of the suspected fluid add 1 fluid ounce of chloroform (or in like proportion with smaller quantities), and allow it to stand 24 hours, frequently agitating; then allow the mixture to subside, carefully separate the chloroform with a funnel, and filter it through bibulous paper; evaporate the chloroformic solution, spontaneously, in a watch glass, to dryness. A small pellet of lint about half the size of a pea, made loose by teasing out the fibers, and moistened with a drop of olive oil, is gently rubbed over the surface of the watch glass so as to mop off the whole of the film of extractive matter, then applied upon the arm, covered with a piece of goldbeater's skin, and allowed to remain on the arm for 3 or 4 hours. Then remove the lint, wipe off the surface of the arm upon which it had been applied, with chloroform, and if the suspected fluid contained cantharides, rubefaction and vesication will be observed. By this process, 1 grain of cantharides, equal to about 1/250 of a grain of cantharidin, may be detected in solution.

Cantharidin (C10H12O4), is an anhydride of cantharidic acid (C10H14O5), which forms a line of salts called cantharidates. When these salts are warmed with an acid, cantharidin is regenerated as an insoluble compound. Cantharidin, by prolonged heating with hydriodic acid, is converted into cantharic acid (C10H12O4), a crystalline monobasic acid to which the double formula (C20H24O8), was assigned by Krafft, its discoverer. A solution of this substance in glycerin does not vesicate. All these compounds are derivatives of the hydrocarbon C6H6(CH3)2, which is a hydrogen addition product of ortho-xylene or ortho-dimethyl benzene.

Action, Medical Uses, and Dosage.—In large doses cantharis is narcotic and irritant; in medicinal doses, stimulant and diuretic. The earliest symptom produced by the smaller dose is irritation of the genito-urinary tract, and if continued, or the dose be larger, strangury with burning pain, and voiding of bloody and albuminous urine results. In large doses, its use is dangerous, being attended often by constriction and difficulty in swallowing, and by violent inflammation of the alimentary canal and urinary organs, strangury, irritation of the sexual organs, and in the female, abortion; also, redness of face, heat, hurried respiration, quick, small pulse, headache, delirium, tremors, tetanic convulsions, and coma. Burning pain is felt in the stomach, and nausea and vomiting follow, with abdominal tenderness, violent griping and purging, the stools being bloody or fibrinous. Ptyalism is excessive, there is a cadaverous odor to the breath, and burning thirst is prominent. Upon the genito-urinary tract its effects are very severe, causing severe burning pain in the kidneys and bladder, with first an increased, then a diminished, flow of urine, with constant urging to urinate, and the act attended with great difficulty, the water passing drop by drop. In the male priapism occurs, and occasionally satyriasis and seminal emissions. In the female, genital heat and irritation are characteristic, and sometimes abortion occurs. Genital gangrene may also result. Applied externally, heat, redness, pain, serous effusion, and vesication occur. The serum is albuminous, of a yellowish hue and alkaline reaction. If continued too long, or even until complete vesication has occurred, serious sloughing, and often gangrenous ulceration may occur, and particularly so after measles, typhoids, and in low vital states. Postmortem examination reveals enlarged and engorged kidneys, with desquamative nephritis generally, though the parenchymatous form is sometimes observed. The bladder membranes are red, blistered, or ulcerated, or coated with false membranes. The gastric, as well as the urinary surfaces, are bloody, congested, or inflamed, and present exudates, or are gangrenous. Twenty-four grains of the powder or 1 ounce of the tincture have produced alarming symptoms, and even death. The smallest dose of the tincture of cantharides which has been known to destroy life was 1 ounce, equal to 6 grains of powdered cantharides. There is no known antidote to its poisonous effects, which must be treated on general principles.

Internally, cantharis, in small medicinal doses, acts as a stimulant to the urinary organs. In minute doses it relieves vesical irritation, and this is its best use. Cantharis is sometimes given in chronic gonorrhoea, gleet, leucorrhoea, seminal weakness, paralysis, and chronic inflammation of the bladder. In cystitis it is valuable to relieve teasing and tenesmus; and in the daytime enuresis of women, due to partial sphincter paralysis, it serves a useful purpose when given in minute doses. R Specific cantharis gtt. x; aqua, fl℥ iv. Mix. A teaspoonful every hour. It has also been reputed useful in the anasarcous swellings succeeding scarlatina, diabetes, scaly cutaneous eruptions, chronic eczema, incontinence of urine, amenorrhoea, etc. Thirty drops of solution of potassa, given every hour, is said to be an effectual remedy in cantharidal strangury (see Tinctura Cantharidis).

Externally, cantharides cause redness, vesication, suppuration or sloughing, according to the length of contact with the integuments. Their most general use is to produce vesication. Blisters are sometimes beneficial in tic-doloreux, sciatica, local chronic inflammations, diseases of the brain, chest, and abdomen, to excite the languid action of vessels, in retrocession of exanthematous affections, and to rouse from general defective sensibility, as in typhoid fever. In their application to children, much care should be observed, especially in typhoid conditions, exanthemata, and where a tendency to sloughing exists. As a rule, blisters are not well thought of by the majority of our practitioners, though occasionally they are deemed of value. A piece of white paper soaked with cantharidin, which is greenish and liquid, laid on the part, and covered with a compress, and confined by means of a bandage, will vesicate in 3 or 4 hours. A vesicating oil has been recommended by E. Dupuy, prepared as follows: To 1 part of pulverized cantharides add, in a close vessel, a mixture of chloroform and castor oil, of each, by weight, 1 1/2 parts; after some hours, transfer the ingredients to a glass apparatus, and displace the liquid in the usual way; it will amount to about two-thirds of the original bulk of the liquid employed. A few drops of this vesicating oil applied to the arm of an adult will produce a perfect blister in about 8 hours. It is easy of application on any surface, holds the vesicating agent free from the disagreeable concomitants of the ordinary fly blister, and retains the cantharides in a soluble state. Its action will probably be favored by the use of oil silk over the application of it to the skin. Cantharidal collodion is now generally preferred to other vesicating preparations of cantharis.

The dose of powdered cantharides is from 1/2 to 2 grains; of specific cantharis, 3 to 10 drops in water; tincture of cantharis, 10 to 60 drops, 4 times a day. For specific purposes the minute dose is preferred.

Specific Indications and Uses.—Vesical irritation, partial sphincter paralysis, with dribbling of urine and teasing desire to urinate, accompanied with tenesmus.

Vesicating and Other Medicinal Insects.—Cantharis vittata, Latrielle; Potato fly.—The potato fly is common to this country, being found principally below 39° north latitude; it appears in July and August, and feeds upon the potato plant. Some seasons the fly exists in great numbers. It resembles the Spanish fly, though somewhat smaller, generally not exceeding half an inch in length. The potato fly, though not so much employed as the Spanish fly, is an excellent substitute for it; indeed, its effects are found to take place more promptly than with the foreign insect, which is probably due to its more recent state. There are several other species of the blistering fly in the United States, which are probably not at all inferior to cantharides, as the Cantharis cinerea, C. atrata, C. marginata, C. vulnerata, C. melaena, C. Nuttalli, and other species. The Mylabris bifasciata, from the Cape of Good Hope contains a large amount of cantharidin (Braithwaite, P. J. Proc., xviii, p. 246). Mylabris cichorii and M. lunata are also vesicant. The former is reputed, in Salamis, a cure for hydrophobia, and is thought to have been the ancient cantharis. This species and M. phalerata, have occurred in commerce as Chinese blistering flies. The Lytta Gigas of the East Indies has also been a commercial commodity. These species all contain considerable cantharidin.

These insects may be used in all cases as substitutes for the Spanish fly, as the property they all possess of blistering the skin when in contact with it, is due to the same constituent. The doses will also be the same.

Aenas afer, of Spain, an insect of the beetle order, is said to be fully as great a vesicant as cantharis, and possesses besides, the advantage of operating almost painlessly and without any irritant action upon the renal organs (Br. Med. Jour., 1882).

Blatta orientalis, Linné, Cockroach.—A revived ancient remedy, having been of late years brought forward in Russia as a non-irritating diuretic for albuminuria and other dropsical complaints. The ancients employed a preparation of the insect in oil in various cutaneous maladies. The active principle, which is crystalline, and known as antihydropin (or taracanin), is said to have been isolated by Bogomolow in 1876.

Related entry: Formic acid

Formica rufa, Linné, Red ant.—This insect, which contains formic acid, and from which the latter was first isolated, enters into some European pharmaceutical preparations. Thus the German Pharmacopoeia has Spiritus Formicarum: Alcohol 70, water 26, and formic acid 4 parts. Mix. Dose, 20 to 60 drops. It forms an acid liquid without color. A Tinctura Formicarum is made by taking alcohol 3 parts, and fresh, bruised red ants 2 parts. Digest. This produces a tincture having a brown color. Baths prepared by adding to the water a decoction of red ants was once used in rheumatic and gouty complaints. The spiritus formicarum is employed in Germany internally and locally in paralytic and other nervous disorders.

King's American Dispensatory, 1898, was written by Harvey Wickes Felter, M.D., and John Uri Lloyd, Phr. M., Ph. D.

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