l'septrifilents on animals show that in lee so bum nitrite causes death by its a,tien On the luumoglobin, and not by anv direct loisonous action on the tis sues. A fatal dose of nitrite may be recovered from if the tissues are sup lit I tt ith a sufficiency of oxygen. Very large doses of sodium nitrite (1.3 grammes per kilo of body-weight) eaused death of the animal within fifty minutes, eten t% hen the animal was kept in oxy gen at high pressure, the fatal result be ing due to the action or the drug upon 11 e tissues. The same dose caused death in under twelve minutes, if the animal remained in the air at the ordinary ressure.
Amyl-nitrite and also isobutyl-nitrite NS ere found to eau:se death even in com lressed oxygen, but the time between the administration and the fatal event was five or six times the time required when the animal was in ordinary air. Amyl-nitrite causes death in air solely in virtue of the action of the nitrite group upon the hmmoglobin; in com pressed oxygen death is caused by the amyl group.
Nitroglycerin in mice and rabbits is only FAightly poisonous; in very large doses poisonous effects are produced from the direct action of the drug on the tissues, before any symptoms are iroduced by decomposition of the ht-emo glol in. or nitrite formation. Compressed oxygen in no way relieved the symptoms.
Number of experiments made upon the blood-changes produeed by the nitrites. These drugs convert hmmogdobin not simply into methaemoglobin, but into what appears to be a mixture of met hmmoglobin and nitrie-oxide htemoglo bin. This conversion is never complete in the living body; the maximum of change found at death was 91 per cent., 9 per cent. of the hmmoglobin being left un altered; in non-lethal doses of sodium nitrite 56.5 per cent. of altered haemo globin was found in a rabbit, which afterwaru recovered.
Amyl-nitrite converts hmrnoglobin at first into a mixture of methmmoglobin and nitric-oxide hmmoglobin, but if ex- cess of the drug is allowed to act, a fur ther change into photomethmmoglobin occurs, and still further changes result from a more prolonged action.
In men and other animals after over doses of sodium nitrite the cyanosis is undoubtedly due to the changes in the hmmoglobin; the other symptoms—such as palpitation, throbbing of the head, headache, nausea, and loss of muscular power—are exactly similar to those met with in cases of carbonic-oxide poison ing, and are characteristic effects of de fective oxygen-supply to the tissues.
From the fact that only ten grains or even less are required to produce serious symptoms in ;nen, it would seem that a, much smaller dose per kilo of body weight affects the blood in men than in mice and rabbits. J. Haldane, R. H. Makgill, and A. E. Mavrogordato (Jour. of Phys., Mar., '97).
Poisoning by the Nitrites.—The symp toms of poisoning by amyl-nitrite are throbbing headache, flushed face, sense of heat, tumultuous heart's action, and diminished sensibility, mobility, and re flexes. Recovery has followed from a
dose of 12 grammes (3 drachms). Death mainly occurs as the result of paralysis of the respiratory centres.
Treatment of the poison has been swallowed, evacuation of the stomach is desirable, providing the pa tient is seen soon enough. The recum bent position and an abundance of fresh air may be supplemented advantageously by the use of artificial respiration and the administration of stimulants, strychnine, ergot, and digitalis by hypodermic injec tion, or by the mOuth if the patient can swallow.
In a ease of poisoning by amyl-nitrite cocaine successfully employed as an anti dote. The patient had accidently spilled 46 minims on the bosom of her dress and had not immediately changed it. She complained of the most violent head ache, palpitation, dimness of vision, and yellow vision. Consciousness was re tained, the gait was staggering, and the carotids pulsated violently,. Fifteen and one-half minims of a 5-per-cent.-cocaine solution were injected subcutaneously, and in a few minutes the worst symp toms of the poisoning subsided, and in fifteen minutes quite disappeared. Schil ling (Med. I'ress and Circ., Nov. 29, '93).
Therapeuties.—The general therapeu tic indications of the various members of this group are very similar. The choice of the remedy and the method of admin istration will depend upon the desired rapidity of action and permanence of ef fects, modified by any untoward or char acteristic symptoxn which may follow the administration of any individual member of this group. When rapidity of action is desired, amyl-nitrite claims first place. When a prolonged effect is desired, so dium or potassium nitrite or, better, potassium cobalto-nitritc may be used. Gastric irritation occasionally follows the use of the nitrites of sodium, potassium, and ethyl. Headache more frequently follows the use of the amyl, isobutyl, and propyl compounds, and, less often, after the nitrites of sodium and ethyl. The pulse is most accelerated by the amyl nitrites; sodium and ethyl-nitrites cause only slight acceleration. Isobutyl and secondary propyl compounds are more active in lowering the blood-pressure (Cash). Isobutyl-nitrite is more reliable than amyl-nitrite for the relief of anginal pains (Leech). Ethyl-nitrite and the oflicinal spirit of nitrous ether act espe cially on the skin and kidneys, increasing the perspiration and the secretion of the urine.
The general indications for the ex hibition of the nitrites are primarily: the presence of general or local muscular spasm, and, secondarily, the presence of pain incident thereto. The nitrites are therefore valuable in various cardiac, pul monary, and nervous disorders attended by angiospasm and increased blood-press ure (high arterial tension).