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Atropinae Sulphas (U. S. P.)—Atropine Sulphate.

Related entry: Belladonna.—Belladonna - Atropina (U. S. P.)—Atropine

SYNONYM: Sulphate of atropia.

Preparation.—Sulphate of atropine may be made by dissolving 30 grains of atropine in 18 fluid drachms of pure ether, and then, adding to this, drop by drop, a mixture of 3 grains of sulphuric acid, and 1/2 fluid drachm of alcohol (specific gravity, 0.817), which forms a milky fluid, continuing the addition of the mixture to saturation of the atropine. Then set the liquid aside, and when there is no further precipitate pour off the supernatant ether, and allow the residue to evaporate spontaneously to dryness (M. Ch. Maitre). In this process all the fluids used should be free from water, and the whole manipulation should be conducted in a cool place; the ether will hold any excess of acid or alkali, which, however, may be neutralized by adding a little more atropine or acid, as required.

Description.—Atropine sulphate is in the form of "a white, indistinctly crystalline powder, without odor, having a very bitter, nauseating taste, and permanent in the air. Soluble at 15° C. (59° F.) in 0.4 part of water, 6.2 parts of alcohol, 2270 parts of ether, or 694 parts of chloroform. At 187° C. (309° F.) the salt melts, forming a brownish-yellow liquid. When ignited it chars, emits acrid vapors, and is completely consumed. The salt is neutral to litmus paper. On adding sodium carbonate T.S. to a concentrated aqueous solution of the salt a white precipitate is obtained, which should respond to the reactions and tests given under Atropine (see Atropina). The aqueous solution of the salt yields, with barium chloride T.S., a white precipitate, insoluble in hydrochloric acid"—(U. S. P.). Atropine sulphate or its solution should strongly dilate the pupil when applied to the eye. This salt is soluble in about 3 parts of glycerin.

Action and Toxicology.—The action of belladonna and its chief alkaloids is practically identical, except in degree and rapidity. The first effect of very small doses is to cause dryness and constriction in the throat, with possibly slightly disordered vision and unpleasant sensations in the head, with vertigo and confusion of ideas. Larger doses occasion mydriasis, with dimness of sight, quickened breathing, frontal headache, with mild delirium, and in some individuals a flushing of the surface with a rash closely resembling that of scarlatina, though lacking the punctations of that eruption, and rarely causing desquamation. If toxic doses be taken these symptoms are intensified. Dimness, or total loss of sight, and extreme pupillary dilatation, with brilliant, staring eyes, headache, and a peculiar delirium ensue. The latter consists of fancies and illusions, hallucinations, and other phantasmagoria, with laughter and gayety, or the cerebral disturbance may lead to violent and furious delirium, with fighting propensities. The respiration is decidedly increased, as well as the frequency of the pulse, which is now hard and small, and the body temperature rises from 1/2° to 1° F. The latter falls, however, when vaso-motor paresis takes place. These symptoms are followed by a well-marked second, or paralytic stage, with muscular weakness, and incoordination and motor paralysis, though sensation is not lost, but is, in a measure, diminished. Stupor, collapse, with feeble pulse, cold surface, and shallow, weak respiration supervene, and death takes place by exhaustion of the powers upon which the circulation and respiration depend, asphyxia preponderating as a cause of death. Narcotism never occurs, and convulsions rarely. It will be observed that full medicinal doses cause a febrile state, while toxic doses paralyze. The rapidity of the heart's action is due first to stimulation of the sympathetic cardiac ganglia, and secondarily, to paralysis of the terminal filaments of the vagus—a state of increased motor activity with decreased inhibitory power. The capillaries are contracted, but in poisonous doses dilated, allowing a fall of blood-pressure, and being due to paralysis of muscular layers of the vascular coats. Owing to vaso-motor paresis, the temperature falls from toxic doses. Atropine causes mydriasis when taken internally by being carried in the blood-current directly to the eye and there acting, as when locally applied, by causing paralysis of the terminals of the oculo-motor nerve, and it is thought also by stimulating periphereal filaments of the sympathetic. Small doses of atropine, while probably causing primary dryness of the gastro-intestinal tract, subsequently induce secretion, as is shown by the slight laxative effects of it and belladonna. It also increases tissue waste, and is eliminated almost wholly by the kidneys; and the urine so charged is said to be capable of dilating the pupil of another subject. The voluntary muscles are but little or not at all affected by atropine. A livid or cyanotic countenance is seldom observed in poisoning by atropine. After death the heart, lungs, and brain are found to be overcharged with blood. The treatment in atropine poisoning is the same as for belladonna poisoning. One-half grain killed a middle-aged man, death singularly being delayed until the sixth day; 1 grain hypodermatically proved fatal to another (see Belladonna).

Medical Uses and Dosage.—As a general medicinal agent atropine may be used in cases requiring belladonna, governing the dose accordingly. Such uses will be those named under belladonna. However, it does not fully represent the parent drug. There are certain cases, however, in which atropine will be preferred; in some on account of its special adaptability; in others for its prompter action. It is a powerful stimulant to the vaso-motor centers and to the capillary circulation. It has at least four well-defined fields of action, viz.: to relieve purely nervous pain; to relieve painful spasm of the involuntary muscles; to arrest excessive secretion of saliva, perspiration, and milk; and as a mydriatic. In various forms of neuralgia, where the pain originates in some nervous disorder it acts magically. Thus it is useful, in the order named, in intercostal, trigeminal, and sciatic neuralgia. It often fails in the latter, and the dose must be large (1/50 to 1/20 grain). In neuralgia of the stomach, ovaries, uterus, and in other visceral neuroses it is an efficient remedy. In most instances it should be subcutaneously employed. By combining it with morphine when this is subcutaneously injected (say 1/96 of a grain of atropine) it prevents the faintness, nausea, and tendency to retching occasionally produced by the morphine alone.

Atropine sulphate, in from 2 to 4 per cent warm solution, has been instilled into the ear for the relief of pain in earache, non-suppurative otitis media, and in diffused inflammation of the aural canal. Atropine is specifically antagonistic to excessive secretions of saliva and sweat, hence it is of much value in ptyalism and in the colliquative sweats of phthisis, hectic and other conditions of debility. The dose should be about 1/100 grain. The value of both belladonna and atropine is well established as remedies to check the mammary secretions. Hence it is used both locally and internally. Atropine sulphate gives prompt relief to spasm of the sphincters and tubular organs of the body.

It is chiefly in ophthalmic practice that atropine has gained laurels. It has, however, been objected to on account of the conjunctival irritation and oedema, as well as the dangerous ocular tension sometimes produced, which may imperil the safety of the eye. More recently it has been replaced, to a considerable extent, by homatropine, which is said to be free from some of the disadvantages attending the use of the former.

Sulphate of atropine in solution is preferred to any other salt of this alkaloid for paralyzing the power of accommodation, and for dilating the pupil of the eye, whenever such dilatation is required; but for this purpose the salt must be pure and perfectly free from acid or alcohol, else it is apt to occasion more or less irritation. That made according to the preceding formula with ether will be found advisable. The habit of ordering a solution of atropine, to which a few drops of sulphuric acid are to be added, is objectionable on the above account, when it is designed for application to the eye. An atropine gelatin has been made for the purpose of dilating the pupil, and which is preferred by some oculists to the solution. It consists of a thin layer of gelatin, with which has been mixed some sulphate of atropine. This layer is marked out into discs or squares, each one of which contains about 1/1000 of a grain of sulphate of atropine. One of these discs placed upon the eye, between the ball and the lid, dissolves rapidly and causes dilatation. When it is desired to paralyze the power of accommodation it is prepared of greater strength (see also Lamellae AtropinaeBr.). It is largely used where inspection of the interior of the globe is sought, and in such operations as cataract, etc. It is a very valuable agent, but may do irreparable injury if inappropriately used. Glaucoma always contraindicates it, and in old people more or less danger attends its use, and even glaucoma may result from it. It is also contraindicated in phlyctenular keratitis after subsidence of the acute phases; in marginal corneal ulcers; in keratitis with superficial vascularity, and in all cases of overtension of the ocular globe. On the other hand, it is the remedy in iritis, from start to finish, and in central perforating corneal ulcers it should be used sufficiently strong and often to insure continuous ciliary paralysis, thereby insuring full dilatation of the pupil, and in the latter instance preventing the iris from adhering to the ulcerated cornea. After operations for cataract, iritis, as a complication, is averted by the use of atropine, and it should be employed also in deep, interstitial keratitis. Intermittent strabismus and consequent eye-strain, as well as chorea from eye-strain, have been corrected by this drug, followed by the selection of the proper lenses.

In the acute stage of phlyctenular keratitis it may be employed to check the flow of tears and sensitiveness' to light, discontinuing the drug as soon as the active inflammation has been subdued. Haziness of the cornea in ophthalmia neonatorum is the danger signal in this trouble, and the prompt use of atropine sulphate will prevent involvement of the corneal and deeper structures of the eye. As an eye remedy it may be used as the exigencies of the case demand. Foltz uses, Rx Atropine sulphate, grs. ss to grs. xvi; water, add fl℥i, the stronger solutions to be used by the physician himself. A solution not stronger than 4 grains to the ounce is dispensed, to be used by the patient 3 times a day. Dilatation is produced in 10 or 15 minutes, and usually persists for 3 or 4 days.

Both atropine and belladonna are antagonistic to opium poisoning, and have been used as strong as 1/12 grain every hour for 5 hours. It is also antagonistic to eserine and pilocarpine, and has been successfully used in strychnine poisoning and chloroform and ether narcosis. Frazer used it (1/120 to 1/60 grain) with morphine sulphate (1/8 to 1/12 grain) hypodermatically before anaesthetizing with chloroform, claiming that it lessens the excitement, takes less chloroform, and longer sustains the action of the latter. Sulphate of atropine (1/100 grain) placed directly upon the sensitive pulp of a tooth is said to promptly check the pain, and a solution has been applied to cancerous ulcers to allay pain. Sulphate of atropine, on account of its greater solubility, is preferred to atropine itself, and both are given in the same-sized doses, 1/200 to 1/20 grain, the larger doses only in extreme cases, as in narcotic poisoning. The solutions should be fresh, as they are apt to develop fungoid growths, with decomposition of the alkaloid. An ointment containing 3 grains of atropine sulphate rubbed upon an ulcer of the neck is said to have produced death in 2 hours.

Sulphate of atropine is generally used in solution in hypodermatic injection, the quantity injected at a time varying from 1/50 to 1/100 of a grain of the salt. The solution may be made by dissolving 1 grain of the sulphate in 4 fluid drachms of distilled water; 4 minims of this contain 1/60 of a grain of the salt; the amount to commence with is 2 minims, which may be cautiously increased to 3 or 4 minims.

Dr. A. Fleming preferred the following solution of atropine for internal use: Take of atropine, 1 grain; distilled water, 5 drachms. Dissolve thoroughly with the aid of a few drops of diluted hydrochloric acid, and add of rectified spirit sufficient to make 10 drachms. This solution keeps well, is of uniform strength, and is much safer and more efficient than some other preparations of belladonna. Ten minims contain 1/60 of a grain of atropine, which is the commencing dose for an adult; it should be given in a little water, once daily, at bed-time, and on an empty stomach. The dose may be increased daily by 2 or 4 minims until some of the physiological effects are slightly produced, as dry throat, dilated pupil, and dim sight. For children under 1 year the dose is 1 minim; of 2 years, 2 minims; of -three years, 3 minims, and so on up to ten years, when 10 minims may be given. It is, however, too dangerous, as an internal medicine, for children, minute doses of belladonna being preferable. Atropine should never be given in pill form, lest from slow or deficient solution it may accumulate in the stomach or bowels, giving rise to severe atropism.

Related Salts of Atropine.—ATROPINAE VALERIANAS. Valerianate of atropine may be made by dissolving a sufficient quantity of monohydrated valerianic acid in a sufficient quantity of pure ether, saturating this solution with atropine, and allowing the liquid to spontaneously evaporate. The salt is deposited in the form of light, white scales, consisting of a mass of small crystals, which is very soluble in water, less so in alcohol or ether, which fuses at 32.2° C. (90° F.) and becomes yellow by exposure to light and air.

M. Michea recommended the valerianate of atropine in spasmodic or convulsive diseases, in doses of a milligramme per day for an adult, on commencing its use; he considered it superior to either valerian or belladonna, on account of its small dose and its certainty of action. It is also recommended in various chronic nervous complaints. The dose is 1/60 to 1/250 of a grain, repeated 2 or 3 times a day.

ATROPINAE SALICYLAS.—Salicylate of atropine forms in deliquescent, non-crystalline, colloidal masses, soluble in water and alcohol, and must be kept in securely-stoppered bottles. It may be prepared by taking a little more than 2 parts (288 grains) of atropine and 1 part of salicylic acid (137 grains) and dissolving them in water (20 ounces), and gently evaporating the solution. When pure it is reputed to act more efficiently and with greater rapidity than sulphate of atropine. The dose is the same as for the latter salt.

ATROPINAE SANTONICUM.—Atropine santonate is formed by the union of atropine and santonic acid. It forms an amorphous powder unaffected by atmospheric moisture, but dissolves with facility in water, forming a solution which, if kept in amber-colored vials (prevents formation of photo-santonic acid), undergoes no change, hence its advantage over the other salts of atropine. Another advantage is that it is said to be perfectly unirritating.

For Scopoline see Related Products, under Belladonna; see also Homatropine hydrobromate.

Photo: Ephedra 2. Related Species and Principles.Ephedra vulgaris. Japan. A plant of the order Gentianae, from which Nagai of Tokio isolated the alkaloid ephedrine (C10H15NO). The latter body produces death in the lower animals by both cardiac and respiratory paralysis. It is a local mydriatic, producing, in 10 per cent solution, an incomplete dilatation of the pupil in from 3/4 to 1 hour, the normal condition being regained in from 6 to 20 hours. The accommodation is scarcely affected. It is not likely to come into general use.

Ephedra monostachya, Linné.—Root and branches used in Siberia in syphilis and gout. The alkaloid, according to Kobert, is non-toxic and non-mydriatic, and therefore unlike ephedrine. This view is supported by P. Spehr (Amer. Jour. Pharm., 1892), who finds the alkaloid to be distinct with the composition C13H19NO, while that of ephedrine is C10H15NO.

Ephedra antisyphilitica, C. A. Meyer.—Mormon tea, Mountain rush, Whore-home tea, Brigham weed. Nevada. Used in gonorrhoea in doses of 1 to 2 fluid drachms of the fluid extract. The medicinal activity depends, in the opinion of Loew, upon a tannin.

GLEDITSCHINE.—Dr. Lautenbach (1878) found this alkaloid in the Gleditschia triacanthos and Gleditschia ferox. The same alkaloid was afterward introduced under the name stenocarpine before it was known to be the product of G. triacanthos. The former name was then restored. The alkaloid was introduced as a local anaesthetic and mydriatic. A solution at one time upon the market was shown to contain cocaine in considerable amounts, besides some atropine or a similar mydriatic, since which gleditschine has fallen into disrepute.

TETRAHYDRO-B-NAPHTHYLAMINE (C10H7H4.NH2).—An extraordinarily powerful local mydriatic, said to be even more powerful than atropine. A 1 to 5 per cent solution is used (Filehne).

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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