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Related post: 1882). The toxicity is low, the fatal dose per vein for dogs being about i Gm. per kilogram. Methyl and ethyl salicylates intravenously produce pulmonary edema by injuring the capillary walls. Therapeutic Effects in Rheumatic Fever and Rheumatic Tonsillitis. The proper administration of salicylates controls the manifestations of this disease in a most remarkable manner in nearly all typical cases so uniformly that failure throws suspicion on the diagnosis: the pain and fever disappear; the local inflammation, the immobility, swelling and red- ness subside; the general condition of the patient is vastly improved; and the disease is under complete control in one to at most five days. These benefits last only so long as the patient is kept salicylated and relapses occur when this is discontinued. According to statistics, the total duration of the disease, as judged by the stay in the hospital, is not affected (J. L. Miller, 1914). The rheumatic cardiac lesions are not relieved directly (Vulpian, 1880). Indirectly the salicylate treatment doubtless has an important tendency in this direction by favoring rest and avoiding the extra tax of fever, pain and insomnia. Efficiency in Related Conditions. Salicylates are much less certain in atypical subacute, chronic, and muscular rheumatism, lumbago, etc., although they usually have some analgesic effect. In acute gout they are often quite effective (Vulpian, 1880). They are notably ineffi- cient in scarlatinal and gonorrheal arthritis (G. See, 1877 ; Stockman, 1906). They are also used in headache, neuralgias, sciatica, tabes and other similar pains, but with inconstant results. In chorea it is difficult to prove any benefits. Response in Different Affections. In the routine statistics of Hanzlik, 1913, in 132 cases of rheumatic fever, salicylates gave complete relief in 82 per cent., partial relief in 16.5 per cent., and failed' in only 1.5 per cent. In subacute rheumatism, thirty cases, it gave complete relief in 53 per cent.; partial in 30 per cent.; failures in 17 per cent. In sciatica, eleven cases, it did not give complete relief in any, failed com- pletely in 27 per cent., and afforded partial relief in 73 per cent. Mechanism, of Action. This has been attributed to the general anal- gesic effect; and to a specific germicidal action on the hypothetic organisms of rheumatic fever. The present data do not suffice to establish either of these views. The enormous doses which are required; the small efficiency of other antipyretics and analgesics; the relative inefficiency of the salicylates in other forms of arthritis all these facts point to a specific action on the infecting agent. Against this view speak the prompt recurrence of the symptoms if the salicylate is discontinued and the failure to prevent the cardiac infection. In rabbits, the prophylactic use of salicyl does not prevent or even influence arthritis from intravenous injection of rheumatic hemolytic streptococci (Miller, 1914; Davis, 1915); but this is not conclusive since the etiology has not been established, and the administration is very different. The analgesic explanation is based on the limited efficiency of SALICYLIC COMPOUNDS 501 salicylates in other painful conditions (Laborde, 1877; Vulpian, 1880); and on the effect of other analgesics in rheumatic fever. Administration. For internal use, the free salicylic acid is too irritant. The sodium salicylate is the most commonly used, notwithstanding its mawkish, nauseant taste. This may be partly disguised by giving the salt in carbonated water, or flavoring with peppermint or wintergreen water. The direct gastric irritation is avoided by adding an equal or double quantity of sodium bicarbonate. To be effective in acute rheumatism, large doses must be administered: i to 1.3 Gm. (15 to 20 gr.) should be given every hour until "toxic" symptoms (tinnitus, nausea, etc.) set in. The administration should then be stopped for twelve hours. After this, i Gm. (15 gr.) should be given every four hours for several weeks, keeping the patient in bed as long as possible. As a prophylactic treatment, i Gm. (15 gr.) may be given three times a day for a week in every month. If the sodium salicylate is not tolerated, oil of gaultheria or aspirin may be substituted. Oil of gaul- theria also gives some relief when applied externally to the affected joints. Hypodermic injections are used by Seibert, 1911, 10 c.c. of 20 per cent, sodium salicylate per 100 pounds of body-weight, every twelve hours; to avoid pain, cocain may be injected before. R. T. Williams, 1913, uses it intramuscularly, 8 per cent., with but little pain. Considering the prompt absorption, these special methods are usually superfluous. Rectal Administration. This is preferred by Heyn, 1914, as being more prompt and less disagreeable. He gives a cleansing soap-sud enema. When it has taken effect, it is followed by the salicylate through a rectal tube, inserted 6 to 8 inches. The first dose is of 8 to n Gm. for men, 6 Gm. for women, in 150 c.c. of water or thin starch, with i c.c. of Tr. Opii. It may be repeated in twelve hours, but usually one enema per day suffices. Salicyl appears in the urine within fifteen to thirty minutes. In very severe cases, the intravenous injection of sodium salicylate may be justified (Mendel, 1905, 1908). Conner, 1914, uses it, with a small needle to avoid thrombosis, in doses of i to 2 Gm., every eight to twelve hours. Cernadas, 1915, advises a solution containing 20 per cent, of sodium salicylate and i per cent, caffein ; injecting this daily, at first 6 c. c., increasing to 10 c.c. The relief is more prompt, and no bad effects have been reported; but it would not be justifiable as a routine measure. "Natural" and Synthetic Salicylates. It is often stated that the syn- thetic sodium salicylate, owing to the presence of supposed impurities, is more toxic and less efficient than that prepared from oil of wintergreen or birch. The evidence for this view, which has been fostered mainly by interested manufacturers, can not stand critical examination. There need be no hesitation in employing the much more economical synthetic Tetracycline Hydrochloride Ointment prod- uct (Rep. Counc. Pharm. Chem., 1913; J.A.M.A., 61: 979). The literature of the subject and its uncritical status have been fully discussed by Eggleston, 1912. Various impurities have been announced in synthetic salicylates, especially cresotic acids, phenol, para-hydroxybenzoic acid, and hydroxy-isophthalic acid; but the evidence for their presence is not convincing. However this may be, Hilpert, 1913, showed that at the present time even the cheapest commercial samples are quite as pure as the most expensive. Waddell, 1911, proved that the effects of natural and synthetic salicylates on animals are quantitatively alike; and the coopera- tive clinical tests, instituted by the Counc. Pharm. and Chem., arranged so as to exclude all bias, showed that their effects on patients are indistinguishable (Hewlett, 1913). In practice, it is almost impossible to be certain of their source, since the oils of winter- green or birch are very often adulterated, beginning at the still. Relation of Constitution to Specific 'Anti-rheumatic Action. Phenol, CeHirOH, is quite inactive. Benzoic acid, CeHfCC^H, has a limited efficiency. The OH and CO 2 H groups are both necessary, and must be in the ortho position to obtain the full efficiency. Derivatives which can be converted into salicylic acid in the organism are effective, in proportion Buy Tetracycline Hydrochloride to the ease of their conversion; but if the H of either group is
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