ATROPINE, a poisonous, crystalline alkaloid (see ALKA LOIDS) widely used in medicine. It does not normally occur in nature, but is derived from laevo-hyoscyamine and laevo-hyoscine (see HYOSCYAMINE and HYOSCINE), found in various plants of the nightshade family, as belladonna (Atropa), henbane (Hyo scyamus), thorn-apple (Datura) and Scopolia. Pure atropine, C17H2303N, crystallizes from alcohol on addition of water in col ourless prisms, which melt at I I 8 ° C. It is readily soluble in alcohol or chloroform, less so in ether, and almost insoluble in water. When atropine was first prepared in 1833 the processes in use for the extraction of alkaloids were too crude to avoid racemization of laevo-hyoscyamine, and so the racemic isomeride, atropine, was obtained, and partially racemic mixtures were later on mistaken for new alkaloids, of which "daturine," "duboisine," etc., are examples. Atropine is now made by racemization, with small quantities of alkali, of crude l-hyoscyamine, the best source of which is Egyptian henbane (Hyoscyamus muticus). The alkaloid may be extracted by the process described in the article ALKALOIDS, and is generally purified after racemization by con version into, and re-crystallization of, the neutral oxalate. Atropine forms a series of well-crystallized salts, of which the sulphate is that principally used in medicine. This salt crystallizes in long, slender, colourless needles (which break up on exposure to air to a crystalline powder) and melts at 194° C. Both atropine and hyoscyamine have been synthesized and are known to be respectively the racemic and laevo-tropic esters of tropine (q.v.) and many attempts have been made to improve on them. The most successful attempt of this kind is liomatropine, which is a phenylglycollic ester of tropine, and is a powerful mydriatic, more rapid but also more transient in its action than atropine.
Pharmacology.—When rubbed into the skin with such sub stances as alcohol or glycerine, which are absorbed, atropine paralyses the terminals of the pain-conducting sensory nerves. It acts similarly, though less markedly, upon the nerves governing the secretion of sweat and is therefore a local anaesthetic or ano dyne and an anhidrotic. Being rapidly absorbed into the blood, it acts on nearly every part and function of the nervous system. Its most remarkable action is that upon the terminals of nearly all the secretory nerves in the body. Sweating and secretion of saliva and mucus in the mouth and throat are arrested. But certain nerve fibres from the sympathetic nervous system, which can also cause the secretion of a (specially viscous) saliva, are entirely unaffected by atropine. A curious parallel to this occurs in its action on the eye. The secretions of stomach, intestines, liver, pancreas and kidneys are reduced, though not arrested, as in the other cases. The secretion of mucus by the bronchi and trachea is greatly re duced and their muscular tissue is paralysed. The secretion of milk is much diminished or entirely arrested. Given internally, atropine does not exert any appreciable sedative action upon the sensory nerves.
The action of atropine on the motor nerves is equally important. Those that go to the voluntary muscles are depressed only by very large and dangerous doses. But moderate doses of atropine paralyse the terminals of the nerves of involuntary muscles, whether motor or inhibitory. In the intestine, for instance, are layers of muscle-fibre which are constantly being inhibited by the splanchnic nerves. These are paralysed by atropine, and intestinal peristalsis becomes more active, the muscles being released from nervous control. The motor nerves of the arteries, of the bladder and rectal sphincters, and of the bronchi, are also paralysed by atropine. The action upon the vaso-motor system is fairly clear. Whether affected entirely by action on the nerve terminals, or by an additional influence upon the vaso-motor centre in the medulla oblongata, atropine causes extreme dilatation of the blood-vessels, the skin becomes flushed and there may appear, after large doses, an erythematous rash, which must be carefully distinguished, in cases of supposed belladonna poisoning, from that of scarlet fever : especially as the temperature may be raised and the pulse is very rapid in both conditions. But the first action of atropine is to stimulate the vaso-motor centre—thereby causing temporary con traction of the vessels—and to increase the rapidity of the heart's action, so that the blood-pressure rapidly rises. Though transient, this action is so certain, marked and rapid, as to make the sub cutaneous injection of atropine invaluable in certain conditions. Since the respiratory centre is similarly stimulated, atropine must be regarded as a temporary but efficient respiratory and cardiac stimulant.
Toxic doses of atropine—and therefore of belladonna—raise the temperature several degrees. The action is probably nervous. In small therapeutic and in small toxic doses it stimulates the motor apparatus of the spinal cord, just as it stimulates the centres in the medulla oblongata. In large toxic and in lethal doses the activity of the spinal cord is lowered.
No less important than any of the above is the action of atro pine on the cerebrum, a state closely resembling that of delirium tremens being induced. In cases of poisoning the delirium may last for many hours or even days. Thereafter a more or less sleepy state supervenes due to exhaustion after the long period of cerebral excitement. It is to be noted that children who are particularly susceptible to the influence of certain of the other potent alkaloids, such as morphine and strychnine, will take relatively large doses of atropine without ill-effect.
The action of atropine on the eye is of high theoretical and practical importance. The drug affects only the involuntary mus cles of the eye, just as it affects only the involuntary or non-striated portion of the oesophagus. The result of its instillation into the eye—and the same occurs when the atropine has been absorbed elsewhere—is rapidly to cause wide dilatation of the pupil. As a result, the tension of the eyeball is greatly raised. The sight of many an eye has been destroyed by the use of atropine—in ignor ance of this action on the intra-ocular tension—in cases of incip ient 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. The fourth ocular effect of atropine is the production of a slight but definite degree of local anaesthesia of the eyeball. It follows from the above that a patient who is definitely under the influence of atropine will display rapid pulse, dilated pupils, a dry skin and a sense of discomfort, due to dryness of the mouth and throat.
Therapeutics.—The external uses of the drug are mainly anal gesic. The liniment or plaster of belladonna will relieve many forms of local pain; but totally to be reprobated is the use, in order to relieve pain, of belladonna or any other application which affects the skin, in cases where the surgeon may later be re quired to operate. In such cases, it is necessary to use such ano dyne measures as will not interfere with the subsequent demands that may be made of the skin, i.e., that it be aseptic and in a con dition so sound that it is able to undertake the process of healing itself after the operation has been performed. Atropine is uni versally and constantly used in ophthalmic practice in order to dilate the pupil for examination of the retina by the ophthalmo scope, or in cases where the inflamed iris threatens to form adhe sions to neighbouring parts. The drug is of ten replaced in ophthal mology by homatropine (vide supra). The anhidrotic action of atropine is largely employed in controlling the night-sweats char acteristic of pulmonary tuberculosis.
Atropine, used as a plaster or internally, of ten relieves cardiac pain. Professor Schafer recommended the use of atropine prior to the administration of a general anaesthetic, in cases where the action of the vagus nerve upon the heart is to be dreaded. It is of value as an antidote in poisoning by pilocarpine, muscarine (mushroom poisoning), etc.
In cases of whooping-cough or any other condition in which there is spasmodic action of the muscular fibre in the bronchia definition which includes nearly every form of asthma and many cases of bronchitis—atropine is an almost invaluable drug. Not only does it relieve the spasm, but it lessens the amount of secre tion—often dangerously excessive—which is often associated with it. The relief of symptoms in whooping-cough is sharply to be distinguished from any influence on the course of the disease, since the drug does not abbreviate its duration by a single day. In treating an actual and present attack of asthma, it is advisable to give the standardized tincture of belladonna—unless expense is no consideration, in which case atropine may itself be used—in doses of twenty minims every quarter of an hour as long as no evil effects appear. The nocturnal urinary incontinence of children and of adults is frequently relieved by this drug.
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 re spiratory failure. This fact, is, of course, the key to treatment. This consists in the use of emetics or the stomach-pump, with lime-water, which decomposes the alkaloid. These measures are, however, usually rendered nugatory by the very rapid absorption of the alkaloid. Death is to be averted by such measures as will keep the heart and lungs in action until the drug has been excreted by the kidneys. Inject stimulants subcutaneously; give coffee— hot and strong—by the mouth and rectum, or use large doses of caffeine citrate ; and employ artificial respiration. Do not employ such physiological antagonists as pilocarpine or morphine, for the lethal actions of all these drugs exhibit not mutual antagonism but coincidence.