The pharmacologic group of nitrites includes the nitrites of amyl, ethyl, and sodium, and, in addition, certain drugs which are not nitrites, but yield nitrites by their decomposition. The alkali nitrates have no effect upon arterial pressure, but potassium nitrate is a salt which forms nitrites when it is burned, though it does not do so in the body; and nitroglycerin, erythrol tetranitrate, and mannitol hexanitrate are organic nitrates which liberate nitrites in the blood.

Preparations And Doses

Amyl nitrite, amylis nitris, C5H11-No2, dose, 2-5 minims (0.13-0.3 c.c), is an unstable liquid with a banana-like ethereal odor. It is very volatile, and decomposes slowly when exposed to air and light. For convenience, it is sold in capsules or ampules of dark glass, containing two, three, four, or five minims. The drug is employed by inhalation, the vapor being liberated by breaking one of these capsules in a handker-chief or piece of gauze.

Sodium nitrite, sodii nitris, NaNo2, dose, 1 grain (0.06 gm.), is a non-volatile and non-explosive deliquescent salt, which is freely soluble in water (1.4 part). It has an affinity for oxygen, and is used in chemistry as a deoxidizing agent. In the air it gradually oxidizes to nitrate and loses its efficiency; and because of this, is the least certain of the group. When given during the digestive period, i. e., while there is free Hc1 in the stomach, it sets free nitrous acid, which is not only irritating to the stomach, but may be somewhat oxidized and rendered inert before absorption.

Nitroglycerin, glyceryl trinitrate, trinitrin, or glonoin, C3H5-(No3)3, is the volatile, highly explosive liquid which is used in the manufacture of dynamite. It is decomposed and rendered non-explosive by strong alkalis. Its dose is 1/100 grain (0.0006 gm.). Its only official preparation is the spirit of glonoin (spiritus glycerylis nitratis), an alcoholic solution of 1 per cent. by weight of nitroglycerin, the dose of which is 1 minim (0.06 c.c.), which contains about 1/120 grain (0.0005 gm.). It is most commonly employed in the form of tablet triturates or hypodermatic tablets, and, because of its volatility, these may be of variable strength and should be kept in closed bottles.

Erythrol tetranitrate, Ch2ch.Ch2(No3)4, is an unofficial, slightly volatile solid, which is insoluble in water and is highly explosive. A druggist is reported to have had his hand blown off on rubbing it in a mortar. The dose is 1 grain (0.06 gm.), in tablets, which keep best when coated. It is rather expensive.

Spirit of nitrous ether, sweet spirit of niter, is an alcoholic solution of 4 per cent. by weight of ethyl nitrite. Its dose is 30 minims (2 c.c.), well diluted with water. It is too mild a preparation to use as a general arterial dilator, and it is employed chiefly in colds and slight fevers as a diuretic. It is possible that in these conditions it may be of use in counteracting the tendency to raised blood-pressure that goes with fever.

Potassium nitrate, Kno3, saltpeter, niter, is a constituent of gunpowder, but is non-explosive. It is soluble in 3.6 parts of water. The solution is used to saturate unsized (filter) paper or the leaves of stramonium or tobacco; and these, when dry, are burned, and the fumes inhaled for the relief of bronchial asthma. On burning, the nitrate liberates nitrites, which check the asthmatic attack by inducing relaxation of the spasmodically contracted bronchial muscles. The nitrate by itself or simply mixed with other drugs does not burn readily. Some of the papers used in cigarette-making are impregnated with niter to make them burn evenly without bursting into a flame; in this case the niter may incidentally serve the useful purpose of antagonizing the primary rise in blood-pressure caused by nicotine.

Pharmacology

Almost the sole use of nitrites in medicine is to relax constricted arteries and constricted bronchi.

The Arteries

If a nitrite is added to the liquid used in perfusing an isolated viscus or a severed limb, the flow through the viscus or limb is greatly increased, and even doubled or trebled. It is evident, therefore, that the drug acts peripherally to dilate the arterioles to a marked degree. A central action is not a factor in the lowering of the pressure, i. e., there is neither depression of the vasoconstrictor center nor stimulation of the vasodilator center, and Pilcher and Sollmann even find a stimulation of the vasoconstrictor center, probably secondary to the lowered pressure. How much of the peripheral action is on the ends of the nerves and how much on the arterial muscles has not been satifactorily demonstrated; but that the muscular action is the chief one is indicated by the dilatation of the coronary arteries, which have no vasomotor nerves. So the essential action is direct depression of the arterial muscles. The nitrites, therefore, are true arterial dilators. Cameron ascertained that on injecting 1/100 grain (0.6 mg.) of nitroglycerin along with 1/8000 grain (0.0075 mg.) of epinephrine, equivalent to 1/8 minim (0.008 c.c.) of the solution of adrenaline, there was no essential rise or fall in arterial pressure, i. e., these amounts practically neutralized each other physiologically. The action of the nitrites is most marked on the splanchnic arteries, but it is also pronounced in the arteries of the limbs, and in the cerebral and coronary arteries. Voegtlin and Macht obtained prompt relaxation in the coronary arteries, but with strips of medium-sized pulmonary arteries Macht obtained constriction. In arteriosclerosis the fall in arterial pressure is not so readily produced, and when produced, may be maintained for a longer time than normally. Of the surface vessels, those of the head and neck, the blushing area, are especially dilated.

The Arteries 43

Aur.

Ven.

B.P.

Fig. 32. - Nitroglycerin, 0.3 c.c. of the 1 per cent. spirit per kilo, promptly reduced arterial pressure from 105 to 60, and this was followed by an increase in rate from 126 to about 150. (Tracing made by Dr. C. C. Lieb.)