Sodii Salicylas

Sodium Salicylate

Sodium salicylate. Dose, grs. xv— 3 j. In wafer or powder it may be given rapidly until the requisite quantity has been swallowed. Salicylate of soda may be prepared extemporaneously by the addition of salicylic acid to a solution of bicarbonate of sodium. If the alkali is in excess, the resulting solution is brownish or purplish in color, and has a strong odor of wintergreen. This is not repulsive to most patients.

The following is a suitable formula: Rx Acidi salicylici, 3 ij; sodii bicarb., 3 j; aquae, oz ij. M. Sig.: A teaspoonful every two, three, or four hours.

Antagonists and Incompatibles

The mineral acids, the metallic salts, and the preparations of iron in general, are chemically incompatible. From the physiological standpoint, salicylic acid and the salicylate of soda are antagonized by the arterial and cerebral stimulants.

Synergists

The effects of salicylic acid are increased in all directions by the members of the phenol group, by the arterial depressants, and by the anaesthetics and cerebral sedatives.

Physiological Actions

In small doses, salicylic acid may stimulate digestion, but in considerable quantity, especially if frequently repeated, it causes uneasiness at the epigastrium, nausea, and vomiting. This inability of the stomach to dispose of the large doses of salicin, salicylic acid, and salicylate of soda, required in the treatment of certain diseases, is an obstacle to their use. They are diffusible and readily enter the blood. It is in a high degree probable that salicylic acid combines with an alkaline base and enters the blood as a salicylate—as a salicylate of sodium, according to Salkowsky. Binz holds that the free carbonic acid present in the blood must effect the separation of salicylic acid from its combinations, and hence that salicylate of soda must act as salicylic acid. It is well known, of course, that salicylate of soda does not possess the antiseptic property of salicylic acid, and, as both act similarly after their medicinal administration, it seems highly probable that the decomposition just mentioned does actually take place. An observation of Köhler seems to support the theory of Binz. Köhler found that, while ordinary blood containing salicylic acid did not yield it up to ether, the blood of asphyxia, which contains an exceptional quantity of carbonic acid, did yield up its contained salicylic acid to ether. The blood in the vessels unquestionably contains more carbonic acid than that which has been exposed to the air. Salicin, as Senator first demonstrated, under the action of ferments, splits up into saligerine and glucose, and saligerine is readily oxidized into salicylic acid. This process is supposed to occur in the body, and hence the comparative slowness of action of salicin and similarity in its effects to salicylic acid. Spencer, examining the blood of a person taking salicin, only got evidence of the presence of the glucoside but not of the salicylic acid, and in the urine of the same subject found but a small part of the acid which ought to have appeared, whence he concludes that the conversion of salicin into salicylic and salicyluric acids, according to Senator, is but partially accomplished in the organism. These observations adequately explain the superior activity of salicylic acid as compared with salicin.

In health, ordinary doses of salicylic acid and salicylate of sodium have but little effect on the circulation. In the carefully conducted experiments of Ringer and Morshead, made on normal subjects, considerable doses of the acid increased the pulse-rate from ten to twenty beats, but more or less feverishness was produced by the irritant action on the gastro-intestinal mucous membrane. The manometric studies of Köhler demonstrated that this agent lowers the blood-pressure, and this result occurred after division of the vagi, the depressors, and the spinal cord, whence it must be concluded that it accomplishes this result by a direct action on the heart and vaso-motor ganglia

More recent observations by Oltramare show that when salicylic acid is thrown into the veins the first effect is to increase the energy of the systolic contractions, the number of pulsations, and the blood-pressure. These effects, he finds, are due to a direct stimulation of the heart and of the motor centers. Under the influence of increasing doses, the vessels dilate, the blood-pressure falls, and finally the heart is arrested. There is, therefore, a general agreement as to the increase of the action, lowering of the blood-pressure, etc., as studied in animals, and observed on man by Ringer and Morshead. Professor Sée, however, fails to discover any effect by salicylic acid on the heart or blood-pressure, but, as he administered the remedy by the stomach, it is probable that he did not secure admission to the blood of a sufficient amount.

The numerous observations made on the effect of salicylic acid and salicylates on the heat-function are in close accord. In health it is found that, unless toxic doses are taken, the temperature is but slightly or not at all affected. Riess, one of the first to make observations on this point, noted a constant reduction of the normal temperature; but See, Ringer, Fürbringer, and others, agree that in health this agent does not affect the temperature. Riess's conclusions were based on more than four hundred observations of the internal use of salicylic acid, and in twenty-three cases he ascertained a reduction of 1·6° Fahr., produced by five grammes (nearly eighty grains). If fever is present, whether produced artificially by the injection of septic materials, or arising spontaneously, salicylic acid very uniformly effects a considerable reduction. The result, however, is not always the same. That salicylic acid has a decided antipyretic action is denied by Zim-mermann, Wolffberg, and some others; but the weight of testimony is overwhelmingly the other way. It is certain that the degree of antipyretic effect varies in different forms of fever (Bartels, Senator, Nathan, and others), and also according to the individual susceptibility to its action. The phenomena attending the reduction of temperature are worthy of consideration. At the onset of the action, in ten to fifteen minutes after the dose is swallowed, some increase in the heart's action, a feeling of warmth through the system, and flushing of the face with suffusion of the eyes are experienced, then the perspiration begins, appearing first on the face, then on the chest, abdomen, and extremities, and presently becomes profuse. Coincidently with the sweat, the decline in temperature begins, but it continues after the sweating. There is no ratio between the amount of sweating and the reduction of fever-heat, for with much sweating there may be but slight diminution in the temperature, and with little sweating a marked decline. In febrile cases the decline of temperature varies from 1° to 6° Fahr. (Riess, Nathan, Bartels, Ewald, and others). The quantity of salicylic acid necessary to effect any considerable reduction of temperature ranges from one to two drachms. The effect is maintained from five to twenty hours, when a repetition of the dose usually becomes necessary. With the first effect of the agent on the heart, the pulse rises, but, as the sweating progresses, more or less slowing of the heart-beat occurs. There are differences of opinion, however, on this point. Thus, Ewald, Riess, Goltdammer, and a few others, hold that the pulse is little if at all affected; but the usual expression is that, after a preliminary rise, there ensues with the perspiration and lowering of the temperature a marked decline in the pulse-rate (Buss, Star-gard, Nathan, Moeli, etc.).

With the first impression of this agent on the respiratory center, the number of respirations is increased, but, with the decline of temperature and of the pulse, they are lessened. The excretion of carbonic acid, Livon shows, is the greater, the larger the dose of salicylic acid, estimated during the period of increased action of the lungs. Under the influence of large doses, accumulation of the acid takes place in the cerebro-spinal fluid, causing an excitation of the roots of the pneumogastric nerve, but the excitation is succeeded by the depression which terminates in arrest of the respiratory function.

As the effects of salicylic acid or salicylate of sodium develop, more or less headache, with a feeling of distention and frontal oppression, is experienced. Buzzing in the ears, dullness of hearing, and even deafness, are usual symptoms when the doses are large. Vision is also affected, the sight becoming dim, or strabismus or ptosis occurs. In one case sudden and complete amaurosis came on (Gatti) after the administration of one hundred and twenty-five grains of salicylate of soda; the pupils were widely dilated, the sclerotic and cornea acquired extreme sensibility, but the retina was unchanged, and the vision fortunately was restored after ten hours without impairment. In other cases, subacute delirium, or delirium with refusal of food, and various delusions (Daly) have occurred while patients were taking considerable doses. Ordinarily, however, the cerebral effects of salicylic acid are not unlike those of quinine. The state of the intracranial circulation which it induces has not been studied. According to Blanchier and Rochefontaine, salicylate of soda depresses the functions of the central nervous system, but the irritability of both sensory and motor nerves and the contractility of muscle remain unimpaired.

Animals to whom salicylate of sodium is administered daily for some time, emaciate rapidly (Chirone and Petrucci). The toxic dose for the dog, ass, and horse, according to Oltramare, is one gramme per kilogramme of the body-weight. Death is due to paralysis of the heart, and not from asphyxia, as has been heretofore supposed (Oltramare). After death the abdominal viscera are intensely congested, unless the medulla be divided, when a marked degree of anaemia succeeds to the hyperaemia. It is this fact chiefly which induces Oltramare to maintain that salicylate of sodium acts on the vaso-motor center in the medulla.

On man as well as on animals sometimes salicylic acid produces serious symptoms. The intoxication, with delirium and delusions which it causes in certain subjects, especially those suffering from acute rheumatism, has been referred to. In drunkards it is especially apt to act unfavorably, bringing on in them violent delirium. In rare instances salicylic acid and the salicylates have induced a condition of collapse, with restlessness, delirium, great dyspnoea, feeble pulse, and involuntary evacuations. The vaso-motor paresis, which is a result of large doses in feeble subjects, may be accompanied by great relaxation of the skin, the rapid formation of bed-sores, etc. Dr. Tuckwell, of the Radcliffe Infirmary, Oxford, gives the following symptoms as occurring in two cases under his observation: "Loud, deep, and sighing respiration; a strange restlessness, gradually increasing to delirium, and not unlike that of delirium tremens, with involuntary evacuation of urine and faeces in the worst of the two cases; a slow and laboring pulse; an olive-green color of the urine."No fatal case, distinctly due to these preparations, has been reported, but many have occurred in which very dangerous symptoms arose; but, fortunately, all disappeared on stopping the administration of the remedy. The existence of albuminuria is an important factor in the causation of bad results (Huber).

The rate of diffusion of salicylic acid has been closely studied by Blanchier and Rochefontaine, with the following results: When injected into the veins of a dog, salicylate of soda appeared in the saliva in four to five minutes; in the urine, eight to ten minutes; and in the bile and pancreatic secretion, in fifteen to twenty minutes. When taken into the stomach, it appeared in the saliva in twenty minutes, and in the urine in forty-five minutes. In man salicylic acid is excreted chiefly, almost wholly, by the kidneys, and appears in the urine in twenty minutes after it is taken into the stomach. It is excreted as salicyluric acid, which may be seen as a deposit at the bottom of the vessel, "of a white, feathery consistence." The urine presents a more or less deep greenish tint. The presence of the acid is readily ascertained by the solution of chloride-of-iron test. To the urine suspected to contain salicylic acid, add slowly, drop by drop, the chloride-of-iron solution; phosphate of iron is first formed, which is whitish in color, but presently, if salicylic acid be present in a free state, a violet color is developed. The urine, during a course of the acid or of the salicylates, frequently contains albumen, due, doubtless, to the irritation of the kidneys as elimination is going on. The facts do not yet warrant any conclusion in regard to the damage which may be permanently inflicted on the kidneys by the prolonged administration of this agent. The influence over the urinary excretion has been examined by Bouchard. There is reason for believing that the urinary water is not augmented, the extractives are somewhat increased, and the phosphates and coloring-matter are unchanged. Prof. See finds that the excretion of uric acid in gouty cases is promoted. It is maintained by others that the amount of urea present in the urine is greater than normal. Livon and J. Bernard have ascertained that salicylic acid, after being thrown into the stomach or into a vein, appears within an hour or two in the saliva, milk, pancreatic secretion, bile, as well as urine, and it was always found in the cerebrospinal fluid. They conclude that it acts locally at these points of contact with the structure of organs. Hence, it appears highly probable that the local stimulation increases the product of those glands through which the acid or its salt passes, but not in the urine, if Bouchard's observations can be relied upon. Albuminuria, according to Gubler, is produced by it in some cases, and temporary impotence has been observed in others.