The ammonium radicle (Nh4) is of dual nature, for, on the one hand, it is strongly alkaline and forms salts homologous with those of the alkali metals, K, Na, Li; and, on the other hand, it can liberate the irritating ammonia gas (Nh3) from its compounds. From a medical point of view, it thus forms two series of compounds - those whose action depends upon free ammonia, and those which act as salts in the body. Those which act as salts may be conveniently considered as of three distinct types, according to their therapeutic uses, viz.: (a) the chloride; (b) the acetate; (c) the salts in which the Nh4 ion is of less importance than the other ions. We shall take up the preparations according to this classification.

I. Those Whose Action Is Dependent Upon Free Ammonia

These include preparations of the gas itself, of the hydroxide, and of the carbonate.

Preparations

1. Stronger water (aqua ammoniae fortior), containing 28 per cent. by weight of Nh3 gas - not used internally.

2. Water (aqua ammoniae, spirit of hartshorn), 10 per cent., 7.5 minims (0.5 c.c.).

3. Aromatic spirit (spiritus ammoniae aromaticus), 9 per cent. of ammonia water and 3.4 per cent. of carbonate, with the aromatic oils of lemon, lavender flowers, and nutmeg. Dose, 30 minims (2 c.c.).

4. Liniment (35 per cent. of ammonia water with cottonseed oil), for external use only.

5. Ammonium carbonate - a mixture of acid ammonium carbonate, Nh4hco3, and ammonium carbamate, Nh4nh2co2. It is wholly soluble in 4 parts of water, but the carbamate portion alone is soluble in alcohol. It is decomposed by hot water. It can yield over 30 per cent. of ammonia gas, but it gives this off more slowly than do the liquid preparations, so is less active. Dose, 3 grains (0.3 gm.).

All these preparations liberate strong ammonia vapor, and in consequence are locally irritating and strongly antacid. For internal use all should be well diluted.

Pharmacologic Action

The Skin

Ammonia water, and much more so the stronger water, is strongly counterirritant. It is capable of producing not only a rubefacient effect, but more marked degrees of irritation, as shown by the formation of vesicles (vesicant effect) or of blisters (epispastic effect). Or it may cause destruction of the tissue (caustic effect).

Mucous Membranes

All the preparations are irritant. Ammonia gas is extremely irritating to eyes, nose, and respiratory passages, and its sudden inhalation may cause a momentary cessation of breathing, with shedding of tears and great discomfort.

Alimentary Tract

The preparations are irritant to mouth, throat, and stomach, and should be well diluted before admin istration. They are carminative and strongly antacid, and if given during the digestive period, may neutralize the hydrochloric acid of the gastric juice, with the formation of ammonium chloride. Being alkaline, they also tend to liquefy mucus.

Absorption

Ammonia gas, when inhaled, is only slightly absorbed, but the liquid preparations are rapidly taken up from the stomach or intestines, and unless changed to chloride by the acid in the stomach, appear in the portal blood as the carbonate or carbamate.

As ammonia is a regular constituent of the alimentary products, and as the carotid blood contains only 2 to 3 mg. of Nh3 in 100 c.c, while the portal blood contains 4 to 6 mg., and, during digestion, even 8 mg., per 100 c.c, it is evident that there is a certain body mechanism for the disposal of alimentary ammonium. It might be well, therefore, to ask ourselves what becomes of ammonia given by mouth as medicine.

If ammonium carbonate is administered by mouth to an animal, there is no increase of Nh3 in the urine, but a proportional increase in urea. Asher injected the carbonate and the tartrate of ammonium into the portal veins of fasting dogs, and found that the lymph in the thoracic duct contained more urea than before, the urea evidently coming from the liver. Bain-bridge, with similar experiments, was unable to confirm Asher's results; but Weintraud, on administering up to 9 grams of ammonium carbonate by mouth, found no increase in the urinary excretion of ammonia, but regularly an increase in the urinary urea proportional to the ammonia administered; and this was in hepatic cirrhosis, where the liver was partly impaired. In other cases of hepatic insufficiency due to various liver diseases more ammonia and a proportionate diminution in the urea, as compared with cases with normal livers, have been found in the urine.

If ammonium carbonate is added to defibrinated blood used to perfuse a recently excised mammalian liver, the urea in the emerging blood is increased 200 or 300 per cent., and ammonium carbonate decreases correspondingly (Starling). In a dog the liver may be experimentally side-tracked by diverting the blood from the portal vein by a cannula to the renal vein or by an Eck fistula, and tying the portal vein to keep its blood out of the liver. The result of this is that more ammonia and less urea are regularly found in the urine, the urine becomes alkaline, and the animal goes into a state of vomiting, thirst, muscular weakness, ataxia, and stupor, followed by cerebral excitement, convulsions, coma, and death in twelve to twenty-four hours. These are the symptoms which result when ammonia is injected directly into the circulation. In these cases the carotid blood contains three or four times the normal amount of ammonia, or about the same proportion as in the portal blood.