Historic Pharmacy Books
This site contains information from many antique pharmacy books. Books like the United States Dispensatory, Christison and Griffeths Dispensatory, often mispelled "Christianson". Many pharmacognosy books and the National Formulary are also found on this site. Below is an example of an insect that was used in the practice of pharmacy.
Spanish Flies, Cantharides; Blistering Flies; Blistering Beetle
CANTHARIS. N. F.
CANTHARIDES Canthar, [Spanish Flies. Russian Flies, Pulvis Canthandis, P. I]
"Cantharides consists of the dried insects, Cantharis vesicatoria (Linne) De Geer (Fam. Meloidea). Cantharides yields not less than 0.6 per cent of cantharidin and not more than 10 per cent of moisture. Caution.—Cantharides with an ammoniacal odor must not be used." N.F.
Cantharides; Blistering Flies; Blistering Beetle. Can-tharides ; Muscle HispanicA. Fr. Cantharide; Insectes coleopteres hcterpmeres; Meloides. Gcr. Spanische Fliegen; Kanthariden; Blasenkafer; Pflasterkafer. It. Cantaride. Sp. Cantarida.
The term Cantharis was employed by the an-cient Greek writers to designate many coleopter-ous insects or beetles. Linnasus gave the title to a genus not including the official blistering insect, placing the latter in the genus Meloe, which, however, has been since divided into sev-eral genera. Geoffrey made the Spanish fly (beetle) the prototype of a new genus, Can-tharis, substituting Cincindela as the title of the Linnasan genus. Fabricius altered the arrange-ment of Geoffrey, and substituted Lytta for Can-tharis as the generic name. The former was adopted by the London College, and at one time was in extensive use; but, the latter, having been
restored by Latreille, is now universally em-ployed. By this naturalist the vesicating insects were grouped in a small tribe, corresponding very nearly with the LinnAean genus Meloe, and dis-tinguished by the title Cantharide, This tribe he divided into eleven genera, among which is Cantharis.
Cantharis vesicatoria is from 15 to 25 ma long, and of a shining, golden-green color. The head is large and heart-shaped, bearing a pair of stout mandibles and filiform antenns; the thorax short and quadrilateral; the wing-sheaths long and flexible, covering brownish membranous wings. When alive, the Spanish flies have a strong, penetrating, fetid odor, compared to that of mice, by which swarms of them may be de-tected at a considerable distance. They attach themselves preferably to certain trees and shrubs, such as the white poplar, privet, ash, elder, and lilac, upon the leaves of which they feed. They ] are most abundant in Spain, Italy, and southern France, but are found also in all the temperate parts of Europe and in western Asia. Accord-ing to the researches of Lichtenstein, the eggs are laid by the female in the latter part of June in small cylindrical holes made in the ground. A week later the larvae hatch out. They are a millimeter long, with two long caudal threads, and of a brown color. After many efforts, Lichtenstein succeeded in getting them to feed on the honey contained in the stomach of bees, : In a few days they changed into milk-white larvae, and about a month after this buried them-selves in the ground, to assume the chrysalis stage and to hatch out the following spring as perfected beetles. In the wild state the larvs are said to crawl up flowers and attach them-selves to bees or other hymenopterous insects; carried by the bee to the hive, the larvs feed upon the young bees and the honey and bee-bread stored up for use. The beetles usually make their appearance in swarms upon the trees in May and June, when they are collected.
The time preferred for collection is in the morning, at sunrise, when they are torpid frora the cold of the night, and easily let go their hold. Persons with their faces protected by masks, and their hands with gloves, shake the trees, or beat them with poles; and the insects are received as they fall upon linen cloths spread underneath. They are then plunged into vine-gar diluted with water, or exposed in sieves to the fumesof ammonia, vinegar, chloroform,bum-I ing sulfur or carbon bisulfide, and, having been I thus deprived of life, are dried either in the sun, or in apartments heated by stoves. This mode of killing the flies by the steam of vinegar is as ancient as the times of Dioscorides and Pliny, When perfectly dry, they are introduced into casks or boxes lined with paper and carefully closed, so as to exclude as much as possible the atmospheric moisture.
Cantharides come chiefly from Spain, south- I ern Russia and Hungary, and other parts of southern Europe, as Sicily, Poland, and ROD-mania. The Russian flies are most esteemed. I They may be distinguished by their greater size, and their color approaching to that of copper, »
In the United States are several species of Cantharis, which have been employed as substi-tutes for C. vesicatoria and found equally effi-cient. For description of unofficial blistering beetles, see U. S. D., 19th ed., p. 284. Vari-ous other allied insects have been used at one time or another as a substitute for the Spanish beetle.
Cantharis vittata Latreille, or potato fly, was recognized by the U. S. P., 1850. It is rather smaller than C. vesicatoria, which it resembles in shape. Its length is about six lines (% inch). The head is light red, with dark spots upon the top; the feelers are black; the elytra or wing-cases are black, with a yellow longitudinal stripe in the center, and with a yellow margin; the thorax is also black, with three yellow lines; and the abdomen and legs, which have the same color, are covered with a cinerous down. It inhabits chiefly the potato vine, and appears about the end of July or beginning of August, in some sea-sons very abundantly. Fahnestock procured 1% per cent of cantharidin from this beetle. (A. J. P., 1878, 51, 298.) This insect must not be confounded with the "potato bug," or Colorado potato beetle (Doryphora decemlineata), which has proved so destructive to potato plants, and which, according to the researches of L. Dem-binski (A. J. P., 1877) contains no cantharidin.
Mylabris cichorii is thought to be one of the insects described by Pliny and Dioscorides under the name of cantharides, and is to this day em-ployed in Italy, Greece, the Levant, Egypt, and China. It is imported to some extent under the name of Chinese blistering fly for the extraction of cantharidin. It is black, with the powder blackish gray and free from shining particles; it yields about 1.25 per cent of cantharidin.
The Br. Add. 1900 under the name of Mylabris recognized not only the dried beetle Mylabris phalerata Pallas (M. sidce Fabr.), but also al-lowed the use in the Colonies of other species of the genus, provided that they yield a similar proportion of cantharidin. Mylabris was char-acterized in the Br. Add. as "usually an inch (twenty-five millimetres) or rather more long, and three-eighths of an inch (nine millimetres) broad; with two long elytra, each three times as long as broad, black with two broad wavy trans-verse orange-colored bands and a large orange-• colored spot at the base of each; one pair of brown membranous wings."
Among other insects that have occasionally found their way into commerce may be men-tioned: Cantharis quadrimaculatus (Mexican Cantharides), Mylabris lunata, M. pustidata (from India), M. bijasciata (from South Africa), Epicauta gorhami (from Japan), Lytta aspersa (from Argentina), etc.
Description and Tests. — "Unground Can-tharides. — From 15 to 25 mm. in length, 5 to 8 mm. in breadth, oblong, somewhat compressed above; externally iridescent, color from brown through olive-brown, green, blue to bluish pur-ple; head triangular, separated into two lateral lobes by a faint median line; mandibles stout and partly concealed; antenna; filiform, of eleven joints, the basal clavate, the second globular, and
the remaining somewhat conical; eyes compara-tively small; prothorax angulate; the first and second pairs of legs with five tarsal joints, the hind pair with four tarsal joints, all legs with two distal claws; posterior wings membranous and yellowish brown or yellowish orange; elytra or wing sheaths each with two parallel lines and finely wrinkled.
"Powdered Cantharides. — Color moderate yel-lowish brown to moderate olive-brown, often with iridescent particles; odor strong, disagreeable; taste slight, afterward acrid; long, pointed spi-cules about 500 microns in length and 20 microns in width at the base; fragments of striated muscles, of chitinous body wall, and of wings and frequently fragments of mites and their eggs.
"Mylabris beetles. — Unground Cantharides should show no insects with black and yellowish orange striped elytra. Moisture. — Determine the moisture in the drug as directed for drugs con-taining no constituents volatile at 100° C." N. F.
Dried Spanish flies preserve the form and color, and, to a certain extent, the disagreeable odor, of the living insect. They have an acrid, burn-ing, and urinous taste. If kept perfectly dry, in well-stoppered glass bottles, they retain their activity for a great length of time, but exposed to a damp air they quickly undergo putrefaction, and this change takes place more speedily in the powder. Hence the insects should either be kept whole, and powdered as they are wanted for use, or, if kept in powder, should be well dried im-mediately after pulverization, and preserved in air-tight vessels. They should never be pur-chased in powder, as, independently of the con-sideration just mentioned, they may in this state be more easily adulterated.
Cantharides are apt to be attacked by mites, which feed on the interior soft parts of the body, reducing them to powder, while the hard exterior parts are not affected. An idea was at one time prevalent that the vesicating property of the in-sect was not injured by the worm, which was supposed to devour only the inactive portion. But this has been proved to be a mistake. Chloroform and carbon tetrachloride are among the simplest, safest and best preservatives to prevent the development of insects in drugs. Cantharides will bear a very considerable heat without losing the brilliant color of their elytra; nor is this color extracted by water, alcohol, ether, or the oils, so that the powder might be deprived of all its active principle and yet retain the exterior characters unaltered. The wing cases re-sist putrefaction for a long time, and the shining particles have been detected in the human stom-ach, months after interment.
Constituents. — The activity of cantharides is due to the anhydride cantharidin which was dis-covered by Robiquet in 1810. (See Canthar-idinutn.) There is present also about 12 per cent of a fixed oil and, according to Orfila, a volatile principle, upon which the fetid odor of the fly depends. It is separable by distillation with water. The green color of the wing cases is probably due to light interference of their translucent films of tissue.
Notwithstanding the insolubility of canthar-
idin in water and cold alcohol, the decoction and tincture of cantharides have the medicinal prop-erties of the insect. Cantharidin probably exists in the insect so combined as to be rendered soluble in water and cold alcohol; if as stated by E. Dieterich (1883), formic acid is present in the Spanish fly, it is possible that the solution of the cantharidin is due to its presence.
"Assay. — Place 15 Gm. of Cantharides, in moderately coarse powder, in a pressure bottle of not less than 250 cc. capacity, add 150 cc. of a mixture of benzene, two volumes, and puri-fied benzin, one volume, and then add 2 cc. of hydrochloric acid. Stopper the bottle tightly, shake it well, and allow it to stand for about ten hours. Now gradually warm the bottle and its contents to about 40° C., and maintain it at approximately that temperature with frequent snaking during three hours, avoiding evaporation. Cool the mixture, decant or filter off 100 cc. of the clear solution, and evaporate this rapidly in a tared beaker or wide-necked flask to a volume of about 5 cc. Add 5 cc. of chloroform to the residue and set it aside in a moderately warm place. When the solvent has all evaporated, add to the crystals 10 cc. of a mixture of equal vol-umes of dehydrated alcohol and purified petro-leum benzin, which has previously been saturated with pure cantharidin, allow the mixture to stand during 15 minutes, and then decant the liquid through a pledget of purified cotton. Wash the crystals with successive portions of a saturated solution of cantharidin, similar to that directed above, until free from fat and coloring matter, and pass the washings through the same pledget of purified cotton. Then wash the cotton with a small quantity of warm chloroform to dissolve any adhering crystals, collecting the chloroform in the tared flask or beaker containing the washed crystals, evaporate the solvent with the aid of a current of air, dry the crystals at 60° C. for one-half hour, and weigh. The resulting weight represents the amount of cantharidin obtained from 10 Gm. of Cantharides." N. F.
For other methods of assay see V. S. D., 20th ed., p. 281; also Coll (Rev. Farm., 1931, 73, 17).
Adulterations. — These are not common. Oc-casionally other insects, or even beads, are added, purposely or through carelessness. These may be readily distinguished by their appear-ance. Flies exhausted of their cantharidin have been substituted for the genuine drug. They are worthless, and are to be distinguished by their lack of substance and their yielding a nearly colorless ethereal tincture.
The percentage of cantharidin found in can-tharides furnishes the best test of its virtues.
Uses. — Internally administered, cantharides is a powerful irritant, with a peculiar direction to the urinary and genital organs. Genito-urinary irritation is ordinarily the first symptom pro-duced by small doses of cantharides, and, if the dose has been large enough, it may amount to violent strangury, attended with excruciating pain, and the discharge of bloody urine.
Cantharides or some similar vesicating insect appears to have been used as far back as the
time of Hippocrates in the treatment of dropsy and amenorrhea. While there is no doubt that, by its local irritant effect, cantharides will in-crease the quantity of urine, because of the dan-ger of undue irritation of the kidney, it has been almost completely abandoned in favor of less harmful diuretics.
Because of the priapism seen in cantharides poisoning the drug is often used in sexual im-potence but it is capable of such serious injury that its employment is not often advisable. As an internal remedy, cantharides is of little prac-tical value.
Externally applied, cantharides excites inflam-mation in the skin, which terminates in a copious secretion of serum under the cuticle. It may be employed either as a rubefacient, or to blister. In the former capacity it has no peculiar value, but as an epispastic it is preferred to all other substances. When blisters are allowed to stay on only long enough to irritate the skin, but not to blister, they are known as flying blisters. Used in this way, they are sometimes of service in neuralgias, applied directly over the seat of pain. The chief use of cantharides is to produce true blisters for the relief of various internal inflam-mations as neuritis, peritonitis, pleurisy, etc.
It is possible for enough cantharidin to be absorbed by the raw surface of a blister to cause marked irritation of the genito-urinary tract. In order to avoid such genito-urinary irritation, and also, as much as possible, the pain at the seat of application, the blister should be left on only un-til it distinctly reddens the skin, when a flax-seed poultice may be applied, and in the course if two or three hours the blister is formed. The time necessary for such reddening of the skin is usually from four to six hours, if the cantharides be active. (See Ccratum Cantharidis.)
Toxicology. — Toxic doses of Spanish fly pro-duce obstinate and painful priapism, vomiting, bloody stools, severe pains in the whole ab-dominal region, excessive salivation with a fetid breath, hurried respiration, a hard and frequent pulse, burning thirst, exceeding difficulty of de-glutition, sometimes a dread of liquids, frightful convulsions, tetanus, delirium, and death. Orfila has known twenty-four grains of the powder to prove fatal. Dissection reveals severe and acute inflammatory changes in the kidney, the intes-tines and sometimes the spleen (see /. A. M. A., 1921, 76, 50).
The poisonous effects are to be counteracted by the use of emetics, cathartics, and opiates by the stomach and rectum. Oils somewhat ac-celerate the poisonous action, probably by dis-solving the cantharidin. It would seem probable that activated charcoal might be useful as an antidote, but we know of no definite evidence on this point.
The dose of cantharides may be stated as one-half to one grain (0.032-0.065 Gm.) but it is rarely prescribed.
Storage. — Preserve "in tight containers." N. F.
Off. Prep. — Ceratum Cantharidis; Emplastrum Cantharidis (from Cerate); Tinctura Canthari-dis, N. F.