Atropine

“ Although pilocarpine quickens the pulse of man, it slows, according to Langley, [542] the heart of the warm-blooded animals, and that of the frog. With regard to the frog, Dr. S. Ringer’s researches are confirmatory. With large doses the heart stops in diastole. If to the heart thus slowed, or even when recently stopped, a minute quantity of atropine be applied, it begins to beat again. There is also a most complete antagonism between atropine and pilocarpine in other respects, atropine stopping the excessive perspiration, and relieving the headache and pain about the pubes, &c. ”

“ It is said that so small a quantity as ·0083 mgrm. (1⁄4000 grain) will in fifteen minutes dilate the eye of a rabbit. It is true that atropine also dilates the pupil; but if sufficient of the substance should have been isolated to apply other tests, it can be distinguished from atropine by the fact that the latter gives no immediate precipitate with platinic chloride, whilst hyoscyamine is precipitated by a small quantity of platinic chloride, and dissolved by a larger amount, and also by the characters of the gold salt.
3. HYOSCINE. ”

“ Pharmacology.—When rubbed into the skin with such substances as alcohol or glycerine, which are absorbed, atropine is carried through the epidermis with them, and in this manner—or when simply applied to a raw surface—it paralyses the terminals of the pain-conducting sensory nerves. It acts similarly, though less markedly, upon the nerves which determine the secretion of the perspiration, and is therefore a local anaesthetic or anodyne and an anhidrotic. ”

“ Simply because the criminal put a little atropine, or belladonna, with the morphine. My tests show absolutely the presence of atropine, Dr. Hanson,” said Craig, bowing to the physician.
“The best evidence, however, is yet to come. A second box of six capsules, all intact, was discovered yesterday in the possession of Henry Vandam. I have analysed the capsules. One contains no quinine at all—it is all morphine and atropine. It is, without doubt, precisely similar to the capsule which killed Mrs. Vandam. Another night or so, and Henry Vandam would have died the same death.” ”

“ The artificial atropine is identical with the natural alkaloid. Ladenburg has also formed a series of artificial alkaloids, called tropeines, by uniting the base tropine with different organic acids, as in the case of the compound of mandelic acid and tropine, known as homatropine, an alkaloid of action similar to atropine, but possessing some decided advantages in its use. Piperine has also been made by the uniting of piperidine and piperic acid, and, as piperidine has already been formed from pyridine, we have here a true synthesis also. ”

“ Action on Man.—When atropine is injected subcutaneously, the symptoms, as is usually the case with drugs administered in this manner, may come on immediately, the pupil not unfrequently dilating almost before the injection is finished. This is in no way surprising; but there are instances in which decoctions of datura seeds have been administered by the stomach, and the commencement of symptoms has been as rapid as in poisoning by oxalic or even prussic acid. ”

“ The obvious antidote is atropine, which may often succeed; and the other measures are those usually employed to stimulate the circulation and respiration. Unfortunately the antagonism between physostigmine and atropine is not perfect, and Sir Thomas Fraser has shown that in such cases there comes a time when, if the action of the two drugs be summated, death results sooner than from either alone. Thus atropine will save life after three and a half times the fatal dose of physostigmine has been taken, but will hasten the end if four or more times the fatal dose has been ingested. ”

“ Following the injection of atropine, the rise in uric acid output, that normally follows the ingestion of protein, was inhibited. But in sequence to pilocarpine, an excitant and not like atropine, a depressor of secretory activity, a marked increase in uric acid excretion followed. The contrast in response was naturally translated as striking evidence of the important rôle played by the digestive glands on uric acid excretion; in other words, it was held that the major portion of the endogenous uric acid was the reflex of such intensified glandular action. ”

“ Atropine by hydrolysis, either by heating it with hydrochloric acid or baryta water, is decomposed into tropine and tropic acid:—
On the other hand, by heating tropic acid and tropine together, atropine is regenerated. Hence it is proved by analysis and synthesis, that atropine is tropic acid-tropine, just as aconitine is benzoyl-aconine. Tropic acid has been produced synthetically by boiling β-chlorphenyl-propionic acid with potash, which at once shows its constitutional formula, viz.:—
Tropic acid has a melting-point of 117° to 118°. ”

“ ATROPINAE SULPHAS—SULPHATE OF ATROPHINE
An alkaloid obtained from belladonna. As it occurs in commerce, it is always accompanied by small proportion of hyoscyamine extracted along with it, from which it cannot readily be separated.
Derivation.—Atropine is obtained from a strong tincture of the root.
Properties.—A white crystalline powder, very soluble in water and alcohol.
Dose.—Horses, 1⁄2 to 11⁄2 grs.; cattle, 1 to 2 grs.; sheep and pigs, 1⁄20 to 1⁄12 gr.; dogs, 1⁄150 to 1⁄50 gr. The doses should be considerably reduced when used with morphine. ”

“ In other words, whilst one-fiftieth of a grain may cause unpleasant symptoms, it may need more than a grain to kill. So valuable are certain of the properties of atropine that it is often desirable to give doses of one-twentieth or one-tenth of a grain; but these will never be ventured upon by the practitioner who is ignorant of the great interval between the minimum toxic and the minimum lethal dose. It actually needs twenty to thirty grains of atropine to kill a rabbit: the animal is, however, somewhat exceptional in this regard. ”

“ So, too, with belladonna, and atropine, its active principle, they are a deadly poison for man, but almost without effect on rabbits: the dose of atropine that would suffice to kill ten men would hardly be enough to kill one rabbit. The difference is not so great with respect to morphine, yet morphine specially affects man; hence in this article we will consider only this one opium alkaloid. ”

“ Vinegar is effective as a substitute for sweet-oil. If from eight to twelve hours have elapsed, the physician may rest assured that amanitine is present, and should administer one-sixtieth of a grain of atropine at once."
This atropine is intended to be injected hypodermically, and the treatment repeated every half-hour until one-twentieth of a grain has been given, or the patient's life saved.
Further consideration of the Amanita and its deadly poison and antidote, with details as to treatment in a notable case, will be reserved for the following chapter. ”

“ Again, when this centre is destroyed (which can be done without injury to the optic centres) , the chromatophoric function ceases—the phenomenon of tinctumutation is no longer observable.
That the sympathetic nerves are the carriers of the messages from the optic nerve and the color-changing centre, can be demonstrated by other means than by excision of the nerve. Atropine, to a certain extent, paralyzes the sympathetic when given in sufficiently large doses, and injections of this drug beneath the skin of a frog render the division of the sympathetic unnecessary. ”

“ When the man drew up before the chemist's shop, Chesney sat for a moment reading over the prescription in his hand. Yes, it was perfectly preserved—quite legible. It was a prescription for soluble tablets of morphia for hypodermic use—one grain of morphia, one one-hundred-and-fiftieth of a grain of atropine. The atropine was to prevent nausea. ”

“ Relief is thereby constantly obtained. Smaller doses of the drug should be given three times a day between the attacks.
The nocturnal enuresis or urinary incontinence of children and of adults is frequently relieved by this drug. The excellent toleration of atropine displayed by children must be remembered, and if its use is “pushed” a cure may almost always be expected.
Toxicology.—The symptoms of poisoning by belladonna or atropine are dealt with above. The essential point here to be added is that death takes place from combined cardiac and respiratory failure. ”

“ Meantime, Clark came each day. He had himself a medical degree, and about this time I called him in professionally, together with Alleyne of Cavendish Square, to consultation over Peters. The patient lay in a semi-coma broken by passionate vomitings, and his condition puzzled us all. I formally stated that he took atropine—had been originally poisoned by atropine: but we saw that his present symptoms were not atropine symptoms, but, it almost seemed, of some other vegetable poison, which we could not precisely name. ”

“ Fibrillar muscular twitching of all the muscles of the body are observed. Death follows in all cases from paralysis of the respiration. Experiments (first by Bexold, then by Fraser and Bartholow, and lastly by Schroff) have amply shown that atropine is, to a certain extent, an antidote for physostigmine poisoning. Fraser also maintains an antagonism between strychnine and physostigmine, and Bennet that chloral hydrate is antagonistic to physostigmine. ”

“ General Treatment.—If the patient is "run down" the general system should be built up.
Local Treatment.—One to two per cent solution of Atropine should be put into the eye three to six times a day to keep the pupil dilated and prevent it from adhering to the cornea. Hot fomentations repeated according to the severity of the case and the amount of "easing" they give. A three per cent solution of boric acid should be used for cleansing purposes. The bowels should be regular. The patient should remain in one room. ”

“ The diagnosis of atropine poisoning may be very difficult unless the attention of the medical man be excited by some suspicious circumstance. A child suffering from belladonna rash, with hot dry skin, quick pulse, and reddened fauces, looks not unlike one under an attack of scarlet fever. Further, as before mentioned, some cases are similar to rabies; and again, the garrulous delirium and the hallucinations of an adult are often very similar to those of delirium tremens, as well as tomania. ”

“ The maximum proportion obtained was 0·6 per cent.; this was from root of the thickness of the finger. Large old roots, 7 or 8 years of age, afford from 0·25 to 0·31 per cent. They have besides a smaller proportion of bark than young roots, and it is chiefly in the bark that the alkaloid appears to reside. Manufacturers of atropine employ exclusively the root.
Ludwig and Pfeiffer (1861) , by decomposing atropine with potassium chromate and sulphuric acid, obtained benzoic acid and propylamine. ”

“ Post-mortem Appearances.—The post-mortem appearances do not seem to be characteristic, save in the fact that the pupils remain dilated. The brain is usually hyperæmic, and in one case the absence of moisture seems to have been remarkable. The stomach and intestines may be somewhat irritated if the seeds, leaves, or other parts of the plant have been eaten; but the irritation is not constant if the poisoning has been by pure atropine, and still less is it likely to be present if atropine has been administered subcutaneously. ”

“ A certain preparation for inebriety is said to contain “stramonine”; as no alkaloid has been described and characterized under this name, it is probably only a variant of daturine, which, as has been said, consists of a natural mixture of hyoscyamine and atropine.
To the above may be added the artificial alkaloid homatropine (C10H21NO3) , which has not been found in a plant, but is prepared synthetically; in chemical constitution it is mandelyl-tropeine, atropine being tropyltropeine. ”

“ The sight of many an eye has been destroyed by the use of atropine—in ignorance of this action on the intra-ocular tension—in cases of incipient glaucoma. The use of atropine is absolutely contra-indicated in any case where the intra-ocular tension already is, or threatens to become, unduly high. ”

“ Children are less affected than adults. Of atropine half a grain has proved fatal. Recovery has taken place after five grains of the sulphate.
Fatal Period.—Twelve hours to several days.
Chemical Analysis.—From organic mixtures the alkaloid may be obtained by Stas‘s process, and treated according to Vitali with a little fuming nitric acid, and then dried in a water bath: when cold, it must be moistened with a drop of potassæ dissolved in absolute alcohol. A violet colour changing to red is produced, the violet being characteristic, as strychnia when treated as above gives a red colour. ”

“ Action on Animals.—The action of atropine has been studied on certain beetles, on reptiles (such as the salamander, triton, frogs, and others) , on guinea-pigs, hedgehogs, rats, rabbits, fowls, pigeons, dogs, and cats. Among the mammalia there is no essential difference in the symptoms, but great variation in the relative sensibility; man seems the most sensitive of all, next to man come the carnivora, while the herbivora, and especially the rodents, offer a considerable resistance. According to Falck the lethal dose for a rabbit is at least ·79 mgrm. per kilo. ”