Opium (U. S. P.)—Opium, cont'd.

Continued from previous page.

I. NARCOTINE (Narcotia) (C22H23NO7, Matthiessen and Foster) may be obtained by extracting opium, first with cold ether, which removes wax and fatty matter, then with warm ether, and recrystallizing the narcotine from alcohol. It crystallizes in rhombic prisms, is tasteless and odorless, little soluble in boiling water, soluble in 100 parts of cold, in 20 parts of boiling 85 per cent alcohol, in 166 parts of cold, in 48 parts of warm ether, and in 2.69 parts of chloroform, in 60 parts of acetic ether, in 22 parts of benzol, and 300 parts of amyl alcohol; insoluble in cold, but soluble in hot solution of caustic potash or lime.

Narcotine is a weak base, forming with acids uncrystallizable, bitter, and soluble salts of acid reaction, decomposable by excess of water, or by evaporation if combined with a volatile acid. Concentrated sulphuric acid dissolves narcotine first colorless and then yellow, and later reddish-yellow; the colorless solution, gradually heated, turns orange-red and exhibits beautiful blue-violet streaks, finally a red-violet color. Neutral narcotine solutions, e. g., in chloroform, are optically laevo-rotatory; in acid solution the rotation is reversed to the right. Narcotine, when oxidized with sulphuric acid and manganese dioxide, yields needles of cotarnine (C12H31NO3+H2O), little soluble in water, and crystallizable, bitter opianic acid (C10H10O5., soluble in hot water Wöhler, 1844). The latter acid yields upon further oxidation hemipinic acid (C10H10O6), and upon reduction with nascent hydrogen meconin (C10H10O4). Cotarnine is a soporific, and is also a motor paralyzant. The complete graphic formula of narcotine is now known; according to Roser, it is closely related to hydrastine (see A. R. L. Dohme's report in Western Druggist, 1895, p. 58). The effects of narcotine upon the system are but imperfectly known. Magendie states that a grain of it dissolved in olive oil and administered to a dog, was followed by death in about 24 hours, while 24 grains, dissolved in acetic acid, diluted, produced no effect. It is very probable that pure narcotine does not possess any very active narcotic powers, and that the first experiments were made with an impure article. Undoubtedly, some morphine is often present in narcotine. Three grains of narcotine, dissolved in diluted hydrochloric acid, and repeated 3 times daily, have been strongly recommended as a powerful antiperiodic, acting without occasioning constipation, uneasiness, and cephalalgia, but frequently causing copious diaphoresis (Br. and For. Med. Rev., Vol. VIII, p. 263). Upon animals narcotine exhibits convulsive effects, but not upon man. Bartholow compares its action upon man to the actions of the alkaloids of the berberine class; upon animals to those of strychnine, etc.

II. MORPHINE (Morphia) (C17H19NO3) (see Morphina).—Apomorphine (Apomorphia) (C17H17NO2) is the name given to an artificial base derived from morphine by Matthiessen and Wright. It is white or grayish-white, non-crystalline, but soon turns green when exposed to the air, is partly soluble in water, soluble in alcohol, ether and chloroform, yielding different colored solutions with each menstruum, and in very small doses is a powerful, non-irritant emetic and contrastimulant. Its crystallized hydrochlorate is now official (see Apomorphinae Hydrochloras).

III. CODEINE (Codeia, Methyl-morphine) (C18H21NO3.H2O). (See Codeina.)

IV. NARCEINE (Narceia) (C23H29NO9).—It is obtained from the mother liquors remaining from the preparation of morphine. It crystallizes in rhombic prisms or needles, is first bitter, afterward styptic, and without odor. Very divergent melting points have been found. The crystals contain some water which it is difficult to expel at 100° C. (212° F.). They are soluble in boiling water and boiling alcohol, insoluble in ether, benzol, petroleum ether, slightly soluble in amyl alcohol and chloroform. Narceine is more soluble in diluted alkalies and ammonia water than in cold water. Narceine is a weak base, but forms with diluted acids crystallizable and soluble salts. When exposed to heat, a smell resembling that of herring-brine (trimethylamine) is evolved. Concentrated sulphuric acid colors pure narceine brown, but the solution is light-yellow, and changes to deep red. If rhoeadine, thebaine, or papaverine are present, a blood-red or blue color will result. Narceine dissolves in concentrated nitric acid with blood-red color. Diluted solution of iodine colors it blue. If narceine is treated with a little concentrated sulphuric acid, and a small amount of sodium nitrite is added, a brown-green coloration is formed, turning blue at the edges; upon heating, a blue-violet color arises. The therapeutical properties of narceine are not well known; it is supposed, however, to influence the inferior part of the spinal marrow, diminishing sensation and mobility in the inferior extremities. It was once thought to be equal to morphine, but free from the unpleasant effects of the latter. Five grains or more of it act as a feeble hypnotic in man. It is not convulsant, and by some is regarded as wholly inert.

V. THEBAÏNE (Thebaina of Couerbe, 1835; paxamorphia of Pelletier, 1832) (C19H21NO3), was discovered by Thibouméry, in 1832, in Pelletier's chemical establishment. It may occur in rectangular scales or needles, or crystalline granules. It has an acrid, styptic taste, and is of a strong alkaline reaction, forming water-soluble salts with acids, crystallizable from alcohol and ether. Thebaïne melts at 193° C. (379.4° F.), and becomes negatively electric upon friction. It is insoluble in water and diluted alkalies; soluble in boiling alcohol, and ether, in about 19 parts of benzol and 60 parts of amyl alcohol; little soluble in chloroform, insoluble in petroleum ether. Boiling with diluted hydrochloric acid converts thebaine into the amorphous bases thebenine and thebaïcine. Both turn blue with concentrated sulphuric acid. Thebaïne is dissolved by concentrated sulphuric acid with blood-red color, changing to yellow-red. (See additional reactions of this and all other opium bases in Charles E. Sohn, Dictionary of the Active Principles of Plants, London, 1894; also see discussion of the probable graphic formula of thebaine by Prof. Freund, in Chem. Centralblatt, Vol. II, 1897, p. 314.) Thebenine has the formula C18H19NO3 (Freund).

Thebaïne is considered to be a poison analogous to strychnine, occasioning, in a small dose, tetanic symptoms resembling those produced by that alkaloid. One and one-half grains, hypodermatically, produce in man anodyne and hypnotic effects without nausea or headache, being equal in power to ¼ grain of morphine.

VI. PAPAVERINE (papaverina) (C21H21NO4).—Pure papaverine crystallizes from alcohol in the form of a network of acicular, white crystals, insoluble in water, but readily soluble in boiling alcohol or ether, in 37 parts of benzol and 76 parts of amyl alcohol; also soluble in warm petroleum ether. Chloroform abstracts it both from acid and alkaline solutions (Dragendorff). It melts at 147° C. (291.4° F.). Papaverine forms crystallizable salts with acids, soluble with difficulty in water. From solution of papaverine in diluted hydrochloric acid addition of strong hydrochloric acid precipitates a heavy oil, the hydrochloride, which soon solidifies to a crystallized mass. Papaverine is colored a deep blue by concentrated sulphuric acid; the solution becomes violet and slowly fades. Potassium permanganate colors this solution green, which changes to a slate color. Strong sulphuric acid containing 0.1 per cent of sodium molybdate, produces with papaverine a beautiful violet coloration changing to blue, and fading within 24 hours. Papaverine has been recommended as a sedative and soporific in mental affections, mania, etc., by certain physicians; while on the other hand, others state that it does not possess any therapeutical virtues. The graphic formula of papaverine has been elucidated by Goldschmidt (see Dohme, loc. cit.).

VII. RHOEADINE (C21H21NO6) was discovered by Hesse in 1865. Besides being a constituent of opium, and the ripe capsules of Papaver somniferum, it is found in all parts of Papaver rhoeas. It forms tasteless, non-poisonous, white, prismatic crystals, melting at 232° C. (449.6° F.), and sublimes in the form of long crystals at a slightly higher heat. It is indistinctly alkaline, almost insoluble in water, alcohol, ether, benzene, chloroform, and ammonia water. Moderately strong hydrochloric or sulphuric acids dissolve rhoeadine with a deep purple-red color. This alkaloid is thereby differentiated into a colorless, crystallizable isomer of rhoeadin called rhoeagenine, and a red coloring matter. Rhoeagenine is distinctly basic to litmus, and forms salts with acids. The coloring matter is sufficiently intense to be still visible in a dilution of 1 in 800,000. Rhoeadine is dissolved by concentrated sulphuric acid with olive-green, by concentrated nitric acid with yellow color.

VIII. CRYPTOPINE (Cryptopia) (C21H23NO5. was discovered, in 1867, by T. & H. Smith, of Edinburgh (see process in Amer. Jour. Pharm., 1867, p. 421), in minute, silky, white, hexagonal prisms or plates, inodorous, slightly bitter, but soon followed by a peculiar sense of coolness recalling the taste of oil of peppermint. When heated it is volatile without residue; it fuses at 217.3° C. (422° F.). It is decidedly alkaline, perfectly neutralizing the strongest acids, and forming salts, of which the sulphate, acetate, hydrochlorate, etc., have been obtained in distinct crystals; however, they all have a tendency to form a jelly. Cryptopine is almost insoluble in water, ether, and benzol; it is soluble in alcohol, or chloroform; insoluble in benzin, oil of turpentine, ammonia water, and caustic mineral alkalies, but readily soluble in diluted acetic, nitric, sulphuric, or hydrochloric acids. Concentrated sulphuric acid gives a blue color with it; but the slightest tinge of purple (or blood-red) indicates the presence of thebaïne. A small particle of niter (potassium nitrate) added to the blue acid solution produces a permanent green color. Papaverine would change through green to orange-red. Cryptopine is anodyne and hypnotic, acting upon man similarly to morphine without the disadvantages of the latter. Said to be four times weaker than morphine; upon the lower animals it is reputed tetanizing and convulsant.

As regards the rarer opium bases, laudanine, laudanosine, codamine, protopine, etc., see O. Hesse (Liebig's Annalen, Vol. CLIII, p. 47, and Supplement, Vol. VIII, p. 261); and O. Kauder (Archiv der Pharm., 1890, p. 419), as well as the references given in the above table.

Ɣ IX. MECONIC ACID (C7H4O7.3H2O).—This acid may be obtained from an aqueous infusion of opium by precipitating it with calcium or barium chloride, as calcium or barium meconate, and decomposing these salts by means of sulphuric or oxalic acids (compare Morphina). Meconic acid crystallizes from water in the form of micaceous scales or rhombic prisms, which lose their water of crystallization at 100° C. (212° F.). Meconic acid tastes sour, and reddens blue litmus paper. It is little soluble in cold water, easily soluble in 4 parts of boiling water, also in alcohol; insoluble in chloroform, not easily soluble in ether. Meconic acid is dibasic, and accordingly forms two series of salts with bases; only the neutral alkali and ammonium meconates are soluble in water; the salts of other metals are insoluble. Thus meconic acid forms insoluble white meconates with silver nitrate, barium chloride, and lead acetate, the precipitates being soluble in nitric acid. A green precipitate of copper meconate is formed when solution of meconic acid is mixed with solution of ammoniated copper sulphate. Morphine seems to combine with meconic acid only in one proportion, forming the neutral dimorphine meconate ([C17H19NO3]2.C7H4O7.5H2O) (see Morphinae Bimeconas).

A characteristic reaction for meconic acid consists in the blood-red coloration it yields with a neutral solution of ferric chloride. This reaction is similar to that produced when ferric chloride is mixed with potassium sulphocyanate (rhodanate). The ferric meconate, however, is insoluble in ether, while the ferric rhodanate is soluble; solution of corrosive sublimate destroys the rhodanate of iron, while it does not affect the meconate. Boiling the solution of ferric meconate does not cause a precipitate or discoloration; while solution of ferric acetate which is of a similar color, would precipitate brown ferric oxyacetate, while the solution would become colorless.

When exposed to about 120° C. (248° F.), meconic acid is decomposed into carbonic dioxide and crystallizable comenic acid (C6H4O5., upon further heating, sublimable pyromeconic acid (C5H4O3) is formed, with additional loss of carbon dioxide, water, acetic acid, and benzol. Meconic acid partly undergoes the first-named decomposition even when heated in aqueous solution.

Action and Toxicology.—Opium is narcotic and stimulant, acting under various circumstances as a sedative, antispasmodic, febrifuge, diaphoretic, and an inspissant of the mucous secretions. Topically, it is a direct stimulant and indirect sedative of the nervous, muscular, and vascular systems. A medium dose, taken while in health, augments the volume and velocity of the pulse, increases the heat of the surface, gives energy to the muscles, renders the mind more acute, and produces a general excitement of the whole system: the brain is especially acted upon, the faculties becoming more clear, the ideas more brilliant, precise, and under control, the power of application more intense, the conversational energies augmented, and frequently a state of frenzy or hallucination is induced. After a time this stimulation abates, leaving a calm, careless, indifferent, pleasurable sensation, with a series of obscure fleeting ideas, which is succeeded, after a longer or shorter period, by sleep, which may continue for several hours, and is followed by giddiness, languid pulse, sickness at stomach, cephalalgia, tremblings, want of appetite, and other indications of derangement of the nervous system. Other effects likewise occur during the period of its influence upon the system, thus—the mucous secretions become suspended, constipation is induced, the cutaneous secretion is increased, and the urinary and biliary secretions may be unaffected, or merely inspissated, in consequence of their discharges being impeded. The retention of urine and constipation, sometimes exist for several days. Generally, no serious results occur from this action of opium, except from a repetition of the dose, so often as to impair the vital powers by continuous over-stimulation. The unpleasant symptoms following the sleep caused by opium may be removed by lemon-juice, strong coffee, or a cathartic.

The effects of opium vary in different persons, and not unfrequently in the same individual under dissimilar circumstances. In some persons the smallest dose will cause nausea, emesis, and gastro-intestinal spasm; in others it will occasion feverishness, headache, watchfulness, restlessness, startling, disagreeable visions, delirium, anxiety, and afterward, an aggravated degree of the more familiar subsequent effects of this drug; these phenomena constitute what is called the idiosyncratic action of opium. Though commonly the result of idiosyncrasy, yet these symptoms are often induced in persons with whom opium in general agrees, simply because the specific indications for the drug are unheeded. Lemon-juice or vinegar renders the action of opium more favorable and less liable to produce the above disagreeable consequences. An unpleasant prickling sensation on the surface of the body, or a troublesome itching, occasionally accompanied with a slight eruption, is sometimes produced by opium, or more readily by salts of morphine. Occasionally, the rash resembles that produced by scarlatina, and desquamation follows. Again, the efflorescence may be of an urticarial nature. The narcotic power of opium is lessened by certain states of disease, as in the advanced stage of pneumonia, or peritonitis, by profuse hemorrhage, especially uterine, by severe dysentery, delirium tremens, some varieties of mania, tetanus, and severe pain or spasm of any kind. It is also modified by the conjunction of other remedies; camphor is thought to diminish the chance of its subsequent or idiosyncratic effects; and given with ipecacuanha, three or four times the ordinary hypnotic dose may be administered without inducing sleep, but with the effect of bringing on sweating with much greater certainty. Belladonna is antagonistic in its effects to those of opium and has been used in cases of poisoning by the latter agent, as an antidote; but when used for this purpose the means hereafter named must not be omitted. Persons who are ordinarily very nervous are very susceptible to the effects of opium. Females are more easily impressed by it than males, and it should be remembered that infants are extremely susceptible to it, even very small doses having been energetic enough to produce death. Nursing infants may be narcotized by the mother's milk while opiates are being taken. On account of the imperfect eliminative powers, opium and its derivatives should be cautiously used upon the aged.

Through whatever channel opium is introduced into the body—the stomach, the rectum, a wound, vein, excoriation, blistered surface, etc.—its remote action is exerted on the brain. It acts most energetically when it is promptly absorbed. When opium, or any of its preparations, is applied freely to a blistered, excoriated, or inflamed surface, its effects should be attentively watched, for dangerous accidents have occasionally happened in this way.

In large doses, opium is a poison, producing death if the proper remedies are not promptly and unremittingly resorted to. The state of stimulation and vivacity, if caused at all, is of short duration, being speedily followed by depression of the circulation, and of the functions of the brain, as manifested by diminution of the frequency of the pulse, but not of force, prostration of muscular power, slow, stertorous, and afterward soft or almost imperceptible respiration, flaccidity of the extremities, languor, drowsiness, torpor, or coma, first livid or turgid, afterward pale features, livid lips, excessively contracted pupils, coldness of the limbs, generally retention of the urine, and frequently profuse, cold perspiration, together with an almost entire apathy to external agencies. This state ends in death, unless speedily relieved. Convulsions may precede death, especially in children, and the pupils dilate just previous to death. It is said that in children the strong pupillary contraction may persist until dissolution. Death is due to respiratory paralysis or asphyxia. Post-mortem examination may reveal cerebral congestion, the brain sometimes being ecchymosed in spots. The cerebral convolutions have been observed to be flattened, and serum may or may not be collected in the ventricles and at the base of the brain, between the membranes. Extravasation of blood on the brain is rarely found, but upon cutting the cerebral substance minute drops of dark blood may ooze from the divided capillaries. The vessels of the spinal cord may be engorged with blackish blood. The spleen, liver, heart, and lungs are sometimes filled to distension with dark blood, and this is especially true when convulsions have preceded death. Great lividity of the skin is frequently observed, and the pupils are often dilated. Taylor observes (Med. Jurisprudence, p. 180) that there is nothing specially indicative of opium poisoning but "fullness of the vessels of the brain;" and this is not always present. If vomiting freely occurs before stupor supervenes, there is a fair chance of recovery. Four grains of opium killed a man of thirty-two, convulsions preceding death, while 2 drachms of laudanum have produced death in an adult. Hypodermatically, ⅙ grain of morphine has killed an adult. Instances are common where persons addicted to the morphine or opium habit have taken enormous doses without injury; but in those unaccustomed to these drugs, the ordinarily recognized medicinal doses should never be exceeded, and treatment should always be begun with the minimum amounts. When a toxic dose of morphine is injected, narcotism ensues very speedily. Opium may kill within 2 hours, though from 6 to 18 hours usually lapse before death ensues (Taylor). The majority die in from 6 to 12 hours. It must not be forgotten that death may occur after the patient has apparently recovered, this being due to syncope, or to pulmonary congestion.

The remedies are, emetics of mustard and lobelia seed, zinc or copper sulphate, ipecac, or apomorphine subcutaneously, with strong coffee, stomach-pump, external counter-irritation, cold applications to the head and spine, forced exercise, galvanism, and artificial respiration. As soon as the stomach has been property evacuated by emesis, internal stimulants must be administered, the best of which are brandy and carbonate of ammonium. Alcoholic stimulants should be given in small amounts, lest they increase the narcosis. The importance of keeping the patient in motion must not be overlooked. This may be accomplished by walking the patient between two attendants. The pleadings of the patient to rest must not be heeded, but he should be forced to move and keep awake by flagellations, electric shocks, and alternate dashings of warm and cold water upon the spine. Tickling the throat with a feather may assist in provoking emesis. Sometimes, when vomiting can not be produced, the shock to the nervous system produced by the means employed to prolong wakefulness, will so impress the nerve centers that they will so far recover their powers as to allow emesis to be produced. The respiration must not be allowed to flag. Ammonia may occasionally be inhaled. As before stated, belladonna is antagonistic to opium. Indeed, atropine is regarded as the best antagonist to poisoning by opium and morphine. Repeated small doses, 1/70 to 1/40 grain of atropine should be subcutaneously injected at intervals until the pupils begin to dilate. This method is preferable to giving a large dose at once, and is attended with results not otherwise obtainable. Stramonium may be used; also gelsemium, giving it short of sedation. Strychnine and cocaine have also been advised, and nitrate of amyl has some advocates. Permanganate of potassium is said to destroy the activity of morphine, and thus prevents its toxic effects. This requires further confirmation. As soon as consciousness is once fairly restored, an active cathartic, with the continuation of the forced exercise, generally completes the cure. The same toxicological treatment should be pursued in case of poisoning by any of the salts of morphine.

Physiologically, opium and its chief alkaloid affect chiefly the functions of the cerebro-spinal tract. In man, the cerebral functions are most impressed; in animals, the spinal axis. The motor and sensory, as well as the higher nerve-centers, are affected, and the terminal nerve-organs respond to its action. It, at first, stimulates and then paralyzes the cardiac motor ganglia and the end-organs of the vagus. The action of the heart and arteries are, at first, increased, and, secondarily, lowered by these drugs. The overstimulation of the spinal cord observed in the lower animals is not generally observed in the human species, and, when occurring, children being generally the individuals so affected. Opium depresses the sexual functions, and impotence in the male and cessation of the menses are not uncommon in opium habitues.

Medical Uses and Dosage.—The special uses of opium are so numerous that it is impossible to do more here than mention the most important of them. In all febrile and inflammatory diseases, it was formerly given either alone, or in combination with ipecacuanha to produce diaphoresis. While, in some instances, it will prove useful, as a rule it is now seldom used in fevers, as we possess better agents to accomplish the results formerly sought from the use of opium. In cases of painful inflammatory affections, however, it is of considerable value. But to prescribe opium and its derivatives intelligently, it is necessary to understand the conditions which are benefited by them, and those in which they produce harmful effects. The patient with the hard, small pulse, the dry tongue, dry, contracted skin, the flushed face, bright eye, and contracted pupil, is always injured by the administration of opium. On the contrary, the patient will be benefited when the pulse is soft and open, or when small, the waves are short and give a sensation of fullness and always lacking hardness, the skin is soft, the tongue moist, the face pale, and the eyes dull, expressionless, immobile, or dilated. In the last case, the drug will act kindly, both in relieving pain and spasm, as a cerebral and spinal stimulant, and as a stimulant to the vegetative processes, and one need not fear the untoward effects usually attributed to idiosyncrasy. When, in typhoid and other low fevers, an exhausted state of the nervous system supervenes, then opium, in stimulant doses only, may be employed. In intermittents, it sometimes aids the action of quinine. While it has been used in the exanthematous diseases, to hasten the appearance of the eruptions, this use of it is not extensive, for better agents are possessed by us, and the use of opium in children's affections should be avoided as far as possible.

As an anodyne-diaphoretic opium, with ipecac, is likewise beneficial in rheumatic, neuralgic, and gouty diseases, in nervous irritability, morbid vigilance, restlessness, diarrhoea, and dysentery. Opium, as a pain-reliever, is of inestimable value when properly used, while, when improperly administered, it still relieves the pain, but may mask conditions of disease so that the physician may be unable to properly watch the progress of the case, the amount of pain often being his best guide to the seriousness and extent of the trouble. When opium, in stimulant doses, relieves pain, no untoward results need be expected, for, in these cases, it does not relieve the pain unless indicated. The danger lies in its employment as a sedative and narcotic. Fortunately, neuralgia, in which opium is so extensively and beneficially used, depends, as a rule, upon a state, the symptoms of which are those in which the drug is specifically indicated. There is nervous debility and often anemia, and opium or morphine acts kindly.

As an antispasmodic, opium is valuable in asthma, colic, cholera, hysteria, tetanus, some forms of dyspepsia, spasmodic and convulsive affections, especially in spasms accompanying the passage of biliary and other calculi, or which are present during an attack of nephritis or gout. Not only does opium relieve the pain, but it also relaxes the spasm attending the passage of the concretions. Here large doses may be necessary. In fact, when no contraindications are present, it is one of our most valued agents in spasmodic disorders. Morphine is generally employed in place of opium where pain and spasm are very severe. Hypodermatic injections of full doses of morphine form the best known treatment of puerperal eclampsia; its action may be assisted by the inhalation of chloroform and other internal treatment as indicated. When opium or morphine are previously administered, anaesthetization is more easily accomplished with chloroform, and much less of the latter is required. Opium is often useful after severe surgical operations to prevent shock and irritative febrile reaction. In respiratory and digestive affections opium, when indicated, will allay cough, soothe pain, relieve nausea, overcome tenesmus, and calm nervous irritability. It is of much utility in checking abnormal and increased discharges, as in chronic catarrh, excessive secretions from the pulmonary mucous membranes, diarrhoea, uterine and other hemorrhages, etc. In those painful conditions of the digestive tract, in which the food acts as an irritant and causes distress, bismuth or nux with opium generally relieves. Morphine with bismuth subnitrate is frequently demanded in gastralgia. In diarrhoea, opium is frequently indicated, and its tincture injected into the rectum, with starch-water, is the only agent, sometimes, that will give relief from tenesmus in acute dysentery. At the same time, the proper internal treatment must be pursued. An injection of morphine is the promptest agent for the relief of cholera morbus. In the exhausting choleraic diarrhoea, rendering one liable to an attack of true Asiatic cholera, during the prevalence of that dreaded disease in this country, Prof. Locke employed the following combination with the best of results: Rx Tincture of opium, tincture of camphor, essence of peppermint, tincture of kino, aa, fl℥j; tincture of capsicum, fl℥ss; neutralizing cordial, fl℥iijss. Mix. Dose, a teaspoonful every ½ hour in severe cases, 3 times a day in mild cases. But little of fluids should be taken, and a mustard plaster applied to the abdomen. In true cholera, stimulant injections of morphine often check the cramps, vomiting and diarrhoea. When constipation is due to spasm of the bowels, opium relieves it. Opium, in well-selected cases, is one of the best remedies in peritonitis and enteritis. Aconite, veratrum, and bryonia will also usually be indicated, but opium, in the form of the diaphoretic or Dover's powder, or even morphine, will give rest from pain and peristaltic movements. In nervous affections, opium is a very important remedy, and many of the symptoms of other disorders partake largely of the nervous element. Indeed, it will be found valuable in all symptoms or forms of disease characterized by pain, wakefulness, inflammation, increased nervous excitability, increased mucous secretions, or spasmodic action.

Probably opium formerly killed more individuals suffering from delirium tremens than all other agents combined. This was owing to the enormous doses administered without regard to conditions. If the patient can not sleep or can not take food, he will die; if there is kidney disease, opium will probably kill the patient; if there is a flushed countenance, bloodshot eyes, wild and furious delirium, pain in the head, red and turgid tongue, and full, bounding pulse, opium will kill the delirium tremens patient; if, on the contrary, the skin is relaxed and moist, the circulation feeble, the face pale, and the tongue moist and dirty, opium is a safe remedy, for here it stimulates and sustains the nervous powers, and favors sleep. Here morphine is generally employed in a ⅛ or not more than ¼ grain dose, every 3 or 4 hours until sleep is induced (Locke, Mat. Med., p. 241). In traumatic tetanus opium is less valuable than morphine; the patient should be kept fully under the influence of the latter until the spasms are over. Though opium and its preparations should be carefully used in affections of the heart, it is one of the very best agents for the relief of angina pectoris. Here it, or morphine, which is usually preferred, is to be given in stimulant doses only. Under its use the pain and dyspnoea are relieved, and the action of the heart strengthened. Opium is not a remedy for continuous and persistent dyspnoea, but that form which is paroxysmal and occurring particularly upon going to bed. In asthma, morphine is one of the palliatives, and may be employed until the action of other agents may be obtained. It is occasionally resorted to in alleviating the distressing cough of phthisis. In threatened abortion, from over-exertion or nervous agitation, ½ drachm of tincture of opium, injected into the rectum, frequently prevents the accident. Dover's powder may also be used. Opium may be employed in insomnia, where cerebral stimulation is required. Of all conditions, it is here that the specific indications must be closely followed. The small or stimulant dose only should be given. The same may be said of it in insanity, in the puerperal form of which it seems to give the best service. Opium and morphine are the direct antagonists to the poisonous effects of atropine, belladonna, physostigma, stramonium, and strychnine.

Opium should not be used internally in cases of excessive inflammatory action, without having first allayed this action considerably by other means; or, if opium be administered, it should be combined with ipecacuanha, as in the compound powder of ipecac and opium, for the purpose of modifying its influence and promoting a determination to the surface. In phrenitis, cerebral congestion, accumulation of blood in the vessels of the head, inflammation of the mucous tissues with diminished secretion, and in ordinary states of costiveness, its employment is not proper. If the costiveness be due to spasmodic action, it may then be given as an antispasmodic in combination with a laxative. Opium is often eaten by persons until it becomes a habit exceedingly difficult to overcome; when taken to excess in this manner it may be known by the deadly pale or sallow aspect, with tokens of emaciation, and a gradual loss of the energies and activity of the whole system. A morphine habitue does not regard truth, and will say and do anything to get the coveted drug. Nervousness, trembling, neuralgic pains, insomnia, loss of appetite, spasms, hyperaesthesia, hallucinations, impotence, cessation of the menses, excessive perspiration, and tendency to self-destruction are among the effects of the habitual use of opium or its alkaloid, by mouth or subcutaneously. Some, however, take them for years without uncomfortable effects only when the supply of the drug is deficient. When the habit can be cured it is usually accomplished by the gradual withdrawal of the drug, and the substitution of small amounts of atropine until the full effects of the latter are obtained. Tonics, capsicum, good feeding, amusements, exercise in the open air, and pleasant society do much to assist in the cure. There is, however, a strong tendency to return to the habit. When the nervous system can withstand the shock it is best to wholly withdraw the drug at once. Murrell very properly remarks that "a good cook is half the battle," for good, stimulating, and nourishing food must be taken and assimilated if good results are to be expected. De Quincy, in his work entitled "Confessions of an English Opium-eater," states that he has taken 8,000 drops of laudanum, or 210 grains of opium daily; and attributes his cure of this lamentable vice to the use of the ammoniated tincture of valerian as a substitute for his opiate stimulant. Probably any other stimulant would have answered the same purpose (see also Morphinae Sulphas).

Externally, opium is employed chiefly to subdue pain, and arrest local inflammatory action; it is applied in the form of lotion, liniment, or plaster, and is of service in neuralgia, rheumatism, some forms of cutaneous diseases, irritable blistered surfaces, diseased mucous surfaces, and in erysipelatous inflammations. It is likewise added to topical preparations for inflammation of the eye, and to gonorrhoeal injections. There is much variety of opinion among physicians as to the use of this drug as a medicine, some contending against its use and others in its favor. That it is a useful agent in many diseases, and exerts an influence not possessed by any other one, no person will attempt to deny; neither does it, when given in the proper medicinal doses, leave the seeds of after-disease in the system, as is the case with mercurial preparations, which in small doses decompose the constituents of the body; therefore, although its present results may be disagreeable, yet, as they are not permanent, there is no good reason why we should dispense with an agent so well calculated to lessen the effects of disease upon the human system. When we administer the almost death-like prostrating emetic, lobelia, the energetic, prostrating, and nauseating hydragogue, resin of podophyllum, etc., etc., it is too much like prejudice without reason to oppose opium because its effects continue for a few days, or improper doses and carelessness in its use have resulted in death, and which may, in a degree, be said of every active remedy in the materia medica (J. King). In suppository it is useful in hemorrhoidal and other rectal troubles, as well as some bladder and urethral disorders, and to allay reflex vomiting therefrom.

Dose of opium in pill or powder, from ¼ to 3 grains, according to its influence upon the patient, the character of the disease, and the object to be accomplished. Sometimes larger quantities are given, as in severe tetanic, or other nervous affections, and in cases of severe pain. The medium dose to ease pain and produce sleep, is 1 grain. The dose of the tincture is from 10 to 50 drops. When it can not be taken by mouth, as in cases of persistent vomiting, and in strangury, severe pain accompanying diseases of the kidneys, bowels, or uterus, and painful tenesmus, it may be injected into the rectum with much benefit, adding to it a small quantity of water, flaxseed or elm infusion, starch-water, mucilage of gum Arabic, etc. When thus given the quantity may be twice that exhibited by the mouth—yet the practitioner should be cautious, as some patients are more powerfully influenced by it than others. (For the action of the opium constituents, see respective alkaloids under the chemical composition of opium, and under MORPHINA and CODEINA.)

Specific Indications and Uses.—To give rest from pain and spasm, and to stimulate the vegetative functions and restrain secretions when the pulse is soft and open, or with short waves, the skin soft and moist, and the tongue moist and sometimes dirty.

Some Opium Preparations.—Poppy capsules are much weaker in their action than opium; they are occasionally used in the form of syrup or decoction among children, but are in every way inferior to opium itself prepared similarly. The decoction, or the poppy capsules, are used for emollient and anodyne fomentations (see Papaveris Capsulae).

SYRUP OF POPPIES.—A syrup of poppies may be made by depriving of their seeds, poppy-heads, 9 ounces; reduce them to a coarse powder, moisten them thoroughly with diluted alcohol and digest for 48 hours; then transfer the whole to a percolator, and gradually pour upon it diluted alcohol until 2 pints of the filtered liquor are obtained; then evaporate by means of a water-bath to 8 fluid ounces, filter, add sugar, 15 ounces; proceed in the manner directed for simple syrup. When cool, add best French brandy, 2 fluid ounces, and mix (C. W. Epting). (See also Syrupus Papaveris.)

SYDENHAM'S LAUDANUM.—Sydenham's laudanum is a vinous tincture of opium, made according to the Parisian Codex, by macerating for 2 weeks in 1 pint of sherry wine, 2 ounces of opium, 1 ounce of saffron, and 1 drachm each of bruised cinnamon and cloves; then filter. A fluid drachm of this laudanum is equivalent to 3 grains of opium (see also Tinctura Opii).

ROUSSEAU'S LAUDANUM.—Rousseau's laudanum is made by exposing a vessel, in which 6 ounces of honey have been dissolved in 1 ½ pounds of hot water, to a temperature of about 26.6° C. (80° F.), until fermentation commences; then add 2 ounces of good opium previously diffused in 1 pound of water, and again expose to a temperature of 26.6° C. (80° F.), for a month; express, filter, and evaporate to 5 ounces, to which 1 ounce of alcohol should be added. Six drops of this preparation are equivalent to 1 grain of opium.

BLACK DROP.—Black, or Quaker's drop, is variously made; the Edinburgh formula is: Take of opium, 4 ounces; distilled vinegar, 16 fluid ounces. Cut the opium into small fragments, triturate it into a pulp with a little of the vinegar, add the rest of the vinegar, macerate in a closed vessel for 7 days, and agitate occasionally. Then strain and express strongly, and filter." The aromatics added in some formulae are unnecessary (see also Acetum Opii).

Related Preparation.—PAPINE. A specialty of Battle & Go., of St. Louis, Mo., containing the anodyne principle of opium without the narcotic and convulsive constituents. Used to control pain and acute inflammatory disorders. One fluid drachm, the dose for an adult, equals in pain-relieving power ⅛ grain of morphine; for infants under 1 year, from 2 to 10 drops.

Related Species and Product.—Eschscholtzia californica, Chamisso; California poppy. This papaveraceous plant, the adopted flower of the state of California, is reputed analgesic and soporific without the dangers attending opiates. Prof. G. F. Walz years ago (1844) found in it two alkaloids, one acrid, the other bitter, besides sanguinarine and some succinic acid. Bardet and Adrian, in 1888, found in it a glucosid and two alkaloids, one of which gave the reactions for morphine. According to E. Schmidt and L. Reuter (Pharm. Centralhalle, 1889, pp. 590 and 611), the morphine-like body is protopine, one of the alkaloids of opium. By some the alcoholic extract has been used to the extent of 185 grains in a day, commencing with a 12-grain dose. Its action is pronounced valuable, quieting pain and producing calm sleep. Respiration is depressed by large doses, while toxic quantities impress the spinal cord.

METHYLTHEBAINE (C20H23NO3), a derivative of thebaine, found by physiological tests to act similarly to, but less energetically, than thebaine.

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