Strychninae Sulphas (U. S. P.)—Strychnine Sulphate.
FORMULA: (C21H22N2O2)2H2SO4+5H2O. MOLECULAR WEIGHT: 854.24.
SYNONYM: Strychninae sulphas (U. S. P., 1870).
"Strychnine sulphate should be kept in well-stoppered vials"—(U. S. P.).
Preparation.—To diluted, warm sulphuric acid, add a slight excess of pure powdered strychnine. Filter, and allow to crystallize. Rhombic, neutral, prismatic crystals, containing 5 molecules of water, are deposited upon cooling the saturated, hot solution. By dissolving the neutral sulphate in diluted sulphuric acid, long, thin needles of the acid salt (C21H22N2O2.H2SO4) are formed upon evaporation. Reversedly, the neutral salt may be obtained from the acid salt, by dividing a solution of the latter into two equal parts, precipitating one-half by aqua, ammoniae, and adding this precipitate to the other half (Rammelsberg, Amer. Jour. Pharm., 1881, p. 627; also see M. W. Coleman, ibid., 1883, p. 113).
Description.—The U. S. P. describes the neutral salt as occurring in "colorless or white prismatic crystals, odorless, and having an intensely bitter taste, perceptible even in highly dilute (1 in 700,000) solution. Efflorescent in dry air. Soluble, at 15° C. (59° F.), in 50 parts of water, and in 109 parts of alcohol; in 2 parts of boiling water, and in 8.5 parts of boiling alcohol. Almost insoluble in ether. When heated at 100° C. (212° F.), the salt slowly loses its water of crystallization (10.51 per cent); more rapidly when heated to 110° C. (230° F.). When quickly heated to 200° C. (392° F.), the salt fuses. Upon ignition; it is consumed, leaving no residue"—(U,. S. P.).
Tests.—"On adding potassium or sodium hydrate T.S. to an aqueous solution of the salt, a white precipitate is thrown down, which is insoluble in an excess of the alkali, and which should conform to the reactions and tests of strychnine (see Strychnina). Barium chloride T.S., added to the aqueous solution, throws down a white precipitate, insoluble in hydrochloric acid. On dissolving 0.05 Gm. of strychnine sulphate in 2 Cc. of nitric acid (specific gravity 1.300), in a small test-tube, the acid should not turn more than faintly yellow (limit of brucine)"—(U. S. P.).
Action, Medical Uses, and Dosage.—Nux vomica and strychnine (see also Nux Vomica) act chiefly, if not solely, by stimulating the spinal cord and medulla oblongata, and without affecting the functions of the brain. The terminal nerves and nerve trunks are little, if at all, affected by strychnine, except in very large doses. Even then, its influence is not thought to be marked. The slightest observable effects from small doses are twitches of the muscles of the arms and legs, occurring especially during sleep, accompanied with restlessness, some anxiety, acceleration of the pulse, and generally slight perspiration. Sometimes the action of the bowels is increased, and the discharge of urine is either augmented or discharged more frequently; it likewise promotes the venereal appetite. Large doses occasion very violent starting of the muscles; even a tendency to lockjaw, succeeded by stiffness, weariness, pain or rending in the limbs. In their highest degree, these effects amount to violent tetanic spasms, occurring in frequent fits, with brief intervals of repose, acute sensibility, and dreadful alarm. If the spasms continue, opisthotonos ensues. The risus sardonicus is observed in strychnine poisoning. The convulsions may be so violent as to throw the victim off a bed. Through whatever form or structure strychnine is introduced into the body, it exerts this action more or less, operating with an energy proportioned to the activity of absorption where it is applied. It is supposed to be a cumulative poison like mercury or digitalis, nor does its activity diminish under the influence of habit, as with opium. M. Duclos states that, under the influence of positive electricity, the symptoms of poisoning by strychnine increase, while they lessen or cease altogether when negative electricity is applied. The long-continued use of strychnine, in excessive amounts, tends to impair the digestive organs, and while small amounts favor diuresis, large quantities impair that function by producing spasm of the bladder muscles. Strychnine is eliminated in part by the kidneys, and may also impair the contractile power of the sphincter vesicae. When strychnine kills, it usually does so by causing spasm of the respiratory muscles, producing asphyxia. As some patients are powerfully affected by the smallest doses of this agent, too much caution can not be employed in its administration. Thirty grains of powdered nux vomica (equal to about 1 seed, or 1/3 grain of strychnine), in 2 doses, proved fatal, while death followed the administration of 3 grains of the alcoholic extract; 1/16 grain of strychnine proved fatal to a small child in 4 hours, while 1/2 grain has killed an adult. Toxic symptoms are often produced by so small a dose as 1/12 grain. Poisoning by nux vomica is slower than by strychnine. The usual length of time in which the latter proves fatal is 2 hours, though death has resulted in 15 minutes, and has been delayed 6 hours. If the patient survives longer than 6 hours, he is likely to recover. There are no characteristic internal post-mortem appearances, though, as a rule, there is congestion of the meninges, and the blood throughout the body is black and liquid. The body stiffens after death, and may be arched, with incurvated toes. Rigidity of the body has been known to persist for months.
In poisoning by strychnine or nux vomica, the patient must be kept absolutely quiet, no noises should be permitted, nor should even a draught of air be permitted to strike the body. Apomorphine, hypodermatically, or other emetics, by mouth, should be given to induce vomiting, while lard, sweet oil, milk, charcoal, or tannin, may be given with a view of enveloping the poison or retarding its absorption. The spasms should be controlled with chloroform. Chloral and potassium bromide have also been asserted to be effectual, as have also atropine, tobacco, and nicotine. Physostigma is also useful, but must be carefully employed, lest exhaustion follow its use. This may, however, be guarded against by the use of stimulants. Artificial respiration may be performed, the forcible action required being less likely to produce spasms than light and superficial contact with the skin.
"I would observe here that, 13 years ago, a favorite Newfoundland bitch, with 3 pups about 2 months old, were poisoned by some evil-minded person, by strychnine placed on meat. One of the pups died in the convulsed condition common to the influence of strychnine; the others were attacked with spasmodic twitchings, which continued to increase. From some cause the bitch vomited up her meat, a portion of which was eaten by 2 chickens, about 6 or 8 weeks old. To the bitch and the remaining 2 pups, I gave about a gill of sweet oil to each, followed by about 4 grains of camphor to the mother, and 2 grains to the pups, in some bread. They recovered and were doing well. Of the chickens, one was apparently dying, lying on the ground, wings outspread, mouth open, and with frequent spasmodic jerks; the other trembled and spasmodically staggered around like an intoxicated person. To each of these I gave about a grain of camphor in butter, and fastened them up, and in an hour they had fully recovered. I mention these facts that further inquiries may be made as regards the antidotal power of camphor in poisoning by strychnine. To determine whether strychnine was the poison administered, the meat vomited by the dogs was carefully examined, and strychnine found present. Both dogs and chickens were actively purged. Since the above occurrence, tannin oil, freely given, and camphor, have been found excellent antidotes to strychnine, also the tinctures of iodine, and bromine, and chlorine" (J. King).
Dr. John Bartlett strongly recommends a solution of common salt as an antidote to strychnine poisoning, from the invariable success attending its use with poisoned dogs (Amer. Drug. Cir., Vol. XI, 1868). Folker, in the Lancet, July, 1867, relates an instance where a healthy man had taken over 2 grains of strychnine, who was saved by the use of chloroform, internally and externally, aided by repeated small doses of tincture of aconite. In Amer. Med. Record, 1867, is a case related where a young man, residing at Chardon, Ohio, who had poisoned himself with 3 grains of crystallized strychnine, was saved by the internal use of camphor, and inhalations of chloroform, continued for several hours. The Medical Times and Gazette, May, 1868, also relates a case where a little girl, 4 years of age, had taken strychnine by mistake, and was saved by being kept under the anaesthetic influence of chloroform for a couple of hours. The Med. and Surg. Reporter of Philadelphia, 1867, relates a case where 3 1/2 grains of strychnine had been swallowed, and, in 24 hours, the person was saved by the administration, every 5, 10, and 15 minutes, of 1/2-teaspoonful doses of tincture of Cannabis indica. J. Rosenthal, from the results of experiments upon animals, and having observed that artificial respiration caused the convulsions, arising from the influence of strychnine, to cease, and even saved the animals from dying, is strongly inclined to believe that, if any method can be devised by which artificial respiration can be maintained for a long time, all persons poisoned by strychnine can be saved, if too long a time has not been allowed to elapse from its ingestion. This method, if practicable, is reasonable, as strychnine kills by spasmodically arresting respiration.
Strychnine increases the quantity of the blood in the spinal cord, and, hence, is not useful when there is congestion of the cord; it localizes its action entirely upon the sensitive nerves; it is injurious in epilepsy and paralysis, arising from lesions of the encephalon, or congestion of the spinal cord; it is useless in paralysis agitans; but, in small doses, is useful in slight paralysis, due to white softening of the spinal cord, and in all cases of functional derangement from want of nervous power. It should be employed in paraplegia, without irritation or without increase of the vital properties of the spinal cord, as in cases of reflex paraplegia, and white or non-inflammatory softening of the cord. It should be avoided in paralysis with symptoms of congestion, myelitis, or spinal meningitis. It is more useful in paraplegia than hemiplegia.
Nux vomica is preferred in many gastro-intestinal affections, while strychnine is more generally employed in troubles affecting the nervous system, bladder, heart, and reproductive organs; and the action of the former is chiefly owing to the strychnine it contains. Yet their action differs but slightly, and most largely in degree. The uses of strychnine are those enumerated under Nux Vomica (which see). There are some conditions, however, in which strychnine is to be preferred, chiefly on account of its prompt action. Some that are mentioned under Nux Vomica are here repeated, and other conditions added.
Strychnine may be administered subcutaneously, and is therefore, of great value in threatened heart failure, to prevent surgical shock, and in dyspnoea, to sustain the breathing function when it seems to be dependent most largely upon the influence of the will, as in low fevers and pneumonia. This action is particularly marked in typhoid and asthenic types of disease, with impaired spinal innervation, and imperfect or feeble respiration. Strychnine, hypodermatically, may be used with great advantage in atonic diarrhoea, cholera morbus, and Asiatic Cholera. One-fifth grain, in divided doses, is of marked utility in the cold stage of congestive intermittents, and in ague, with atony of the stomach and impaired innervation. Strychnine is preferred over nux vomica in impotence, from exhaustion or weakness, in urinal incontinence of the young and the aged, and in urinal retention from atony. Strychnine enters largely into the treatment of dipsomania, the sulphate or nitrate being preferred. The latter is said to be effectual in preventing surgical shock. It is antidotal to chloral, morphine, or opium (early stage of poisoning), and in asphyxia from gas or water, or in chloroform narcosis. The semi-paralytic state, produced by excess of bromides or lead, is somewhat relieved by it. Strychnine is of marked value in many nervous affections. Occasionally, it gives good results in tetanus and epilepsy, and, in chorea, it first aggravates, and then frequently cures. Oesophageal spasm and hay-fever are sometimes controlled by it. It has relieved writer's cramp. The forms of paralysis benefited by strychnine are those functional in character, and often reflex from excesses and rheumatism, neuralgia, concussion of the cord, hysteria, etc. In post-diphtheritic paralysis, it is one of our best agents. It relieves obstinate facial neuralgia, when atony is a marked feature.
Strychnine is also useful in hemiplegia, paraplegia, partial paralysis of particular joints or muscles, and of the bladder. The paralyzed muscles are always first affected if they are thrown into spasms at all. If the remedy is to succeed, improvement begins speedily. It must not be used in recent cases of paralysis, or while general reaction prevails; neither when signs exist either of local irritation in the brain or spinal cord, or of determination of blood to the bead. It has been likewise used in various forms of neuralgia, amenorrhoea, dysentery, rheumatism, syphilitic osteocopa, and obstinate constipation. "In the treatment of gleet, urethral stricture, and recent enlargement of the prostate, I have found it a superior remedy, used internally and locally. In dyspepsia, when there is a want of appetite, constipation, and a sensation of epigastric weight after eating, I have found the combination of 1 grain of the alcoholic extract of nux vomica, well triturated with 40 grains of the oleoresin of ptelea, and divided into 20 pills, an excellent remedy. Likewise in dyspepsia connected with impotence, caused by masturbation or venereal disease; the dose is 1 pill, repeated 3 times a day" (John King). Strychnine will also be found advantageous in many uterine diseases, prolapsus uteri, etc. Prof. A. J. Howe found the following powder to produce an anodyne influence in cases of cancer of the uterus, and other severe diseases, attended with extreme pain: Take of sulphate of morphine, 5 grains; sulphate of quinine, 10 grains; strychnine, 1 grain; liquorice powder, 20 grains; mix thoroughly together, and divide into 20 powders, 1 of which may be taken every 4 or 6 hours, according to the urgency of the symptoms. Dr. Alexander Fleming recommended the following solution of strychnine, for internal use, as being much safer and more efficient than the galenical preparations of nux vomica: "Take of strychnine, 4 grains; distilled water, 10 fluid drachms; dissolve the strychnine thoroughly with the aid of a few drops of diluted hydrochloric acid, and then add alcohol, a sufficient quantity to make the whole measure 20 fluid drachms. This is of uniform strength, passes readily into the circulation, and the dose can be apportioned with accuracy. The commencing dose is 10 minims, and contains 1/30 grain of strychnine. It should be given on an empty stomach, and diluted with water, to insure its prompt and easy absorption. As a tonic, the dose is 5 minims, 2 or 3 times a day." He also stated that "strychnine should never be given in pill form, because it is hard of solution in the weak acids of the stomach, and several pills may remain unchanged and accumulate there or in the bowels. A change in the secretions may then dissolve and transport them simultaneously into the blood, and give rise to alarming tetanic symptoms. This is commonly the correct explanation of the so-called cumulative action of strychnine—the sudden solution and absorption of hard pills accumulated in the stomach or bowels." The dose of strychnine is from 1/30 to 1/10 grain, 2 or 3 times a day. It may be rendered more soluble in alcohol or water, by the addition of a few drops of an acid, as acetic, hydrochloric, nitric, or sulphuric.
Specific Indications and Uses.—(See Nux Vomica.) Functional forms of paralysis, due to excesses; atony.
Related Alkaloid.—BRUCINE exerts an influence upon the system very similar to that occasioned by strychnine, but is less energetic. Its dose is from 1/8 to 1/2 grain, 3 or 4 times a day. In the administration of brucine and strychnine, or any of their salts, great caution must be observed, and the patient carefully watched during their use. According to Prof. Brown-Sequard, strychnine and brucine have similar effects. Local anaesthesia is reported from the use of a 5 per cent solution of brucine upon mucous membranes, but not upon the skin.