Preparations

The mildly alkaline salts are the carbonate and the hydroxide. The carbonate is insoluble in water. The salts for systemic action are the chloride and the lactate, both soluble in water, the former being deliquescent. The carbonate (CaC03) comes in two forms - "prepared chalk" (creta praep-arata) and "precipitated chalk" (calcii carbonas praecipitatus). The latter is in the form of a heavy fine powder, may be obtained pure, and is much used in tooth-powders. The former is prepared from native chalk and contains impurities, but because of a cohesive tendency has been much used in liquids for internal use. It comes in heavy, cone-shaped lumps, and is often called "drop-chalk," from its method of manufacture. It constitutes 30 per cent. of compound chalk powder (pulvis cretae compositus); and this is kept on hand for the fresh manufacture of chalk mixture (mistura cretae), dose, 2 drams (8 c.c.). Unfortunately this mixture contains the fermentable substances, sugar and acacia, and does not keep well.

The hydroxide is employed in the form of a saturated solution, known as lime-water (liquor calcis). Lime-water is a very weak preparation, containing only 0.14 per cent. of calcium hydroxide, i. e., about 11 grains to a pint. It is precipitated by heat. To neutralize 1 minim of hydrochloric acid, 1/2 ounce (15 c.c.) is required. On exposure to air it takes up carbon dioxide and forms calcium carbonate, which precipitates. Hence lime-water tends to deteriorate, and samples sometimes contain almost no calcium hydroxide. Before making lime-water the slaked lime should always be washed thoroughly, to remove soluble impurities, as directed in the Pharmacopoeia.

The syrup of the lactophosphate (syrupus calcii lactophos-phatis), dose, 2 drams (8 c.c.), is official.

Action

As shown by numerous experiments calcium is necessary not only for the growth of bone, but also for that of the soft tissues. In adults it is required in amounts equivalent to about 15 grains (1 gm.) of calcium oxide a day. The body obtains its supply of calcium chiefly from drinking-water, eggs, milk and green vegetables, and slightly from animal flesh, cereals, and fruits. Milk contains about 0.17 per cent., i. e., slightly more than lime-water. There is as much calcium in 400 calories of milk as in 10,000 calories of round steak and white 7 bread (Sherman). The absorption of calcium is not very ready, though it is favored by the acid of the gastric juice. From 60 to 80 per cent. of the calcium taken by mouth passes out with the . feces (von Noorden), part of it having been unabsorbed, and part of it absorbed and reexcreted. After a hypodermatic of a calcium salt it quickly appears in the colon and as much as 50 per cent. has been recovered in this way. In the urine the ordinary daily output is from 0.1 to 0.5 gm. per day, and in the feces 0.4 to 0.8 gm. When Soborow gave 8 to 10 gm. of chalk per day, the calcium of the urine rose to 0.7-0.98 gm. According to Beneker, in sickness and all conditions of debility, and in starvation, much more than usual of the calcium and magnesium phosphates may appear in the urine, and sometimes enormous quantities (2 to 4 gm. a day}. Hoppe-Seyler says this excretion is favored by rest in bed, the bones slowly atrophying and giving off lime salts. The bones contain about 4000 times as much calcium as the blood and act as a reserve to keep the calcium of the blood normal. In infant feeding both calcium and fat may be lost by the formation of insoluble calcium soaps in the intestines, and Dubois and Stolte suggest for its prevention the giving of sodium or potassium carbonates or foods yielding excess of alkali. Acid conditions favor excretion by the kidneys rather than by the colon, hence in acidosis from diabetes, and when there is much acid in the food, the urinary output of calcium rises to a high figure.

Loeb found that calcium salts can stop contact irritability of muscle and the hypersensitiveness of the nervous system induced by various salts. They increase the rapidity of action of the coagulating enzymes, especially of the blood and milk. They antagonize the action of potassium salts on the heart. Loeb has recently suggested that the calcium in the blood is for the protection of the cells from acids and sodium, the potassium and calcium making a relative impermeability of the external portion of the protoplasm of the cells. Meltzer states that calcium is capable of correcting the disturbances of the inorganic equilibrium whether these are in the direction of increased irritability or the opposite. Loeb noted that the lack of sufficient calcium or the injection into the animal body of a salt capable of precipitating calcium - e. g., the oxalate or citrate of sodium - results in muscular twitching. MacCallum, Lambert, and Vogel perfused an isolated limb with normal blood dialyzed to remove calcium, and produced extreme hyperexcitability. With blood similarly dialyzed, but with the calcium retained, there was no hyperexcitability.

Tetany has frequently followed removal of the parathyroid glands, and both in tetany and after parathyroidectomy the calcium content of the brain and blood has been found diminished (Quest and MacCallum and Voegtlin). It has also been shown by the last two investigators that the nervous manifestations following parathyroidectomy may be checked by the administration of calcium salts. They suggest that the absence of the parathyroids causes an "impoverishment of the tissues with respect to calcium, and the consequent development of a hyper-excitability of the nervous system, and tetany." Marine and Lenhart found that 5 c.c. of a 5 per cent. solution of CaCl2 resulted in the recovery of a dog from tetany which came on after a thyroid operation.

It is well known that infantile tetany usually appears in those with rickets. Erdheim (1911) reports that extirpation of the parathyroid glands of white rats resulted in the failure of full calcification of dentine and enamel in the growing teeth; but that on transplanting parathyroid glands, the dentine and enamel layers became fully calcified. Erdheim and Canal showed further that after removal of the parathyroids callus formation is retarded. These facts and a number of reported cases of human tetany relieved by calcium lead one to think that calcium-starvation, or disturbance of calcium metabolism through failure of the parathyroids, is an important cause of tetany, and suggest the intravenous use of calcium salts in this disease (Meltzer).

Coagulation Of The Blood

It is an old observation that calcium salts added to the blood outside of the body, or intravenously, increase its coagulability and lessen its coagulation time. But it is still a question whether calcium salts administered by mouth have such an effect. Wright and Paramore (1905) reported a distinct difference within an hour or less; but Addis (1909) found that calcium salts administered by mouth increased the ionizable calcium of the blood, but not sufficiently even from large doses, to alter the coagulability. Rudolf and Cole (1911), after a very careful series of studies, have come to the conclusion that "the free exhibition of calcium lactate by mouth has no appreciable effect upon the coagulation of the blood"; and Van Lier (1912), after taking the coagulation time in 40 persons before and after administration of calcium lactate, has arrived at the same conclusion. Lee and Vincent (1915), however, after several days of 100 grains (6.6 gm.) of calcium lactate daily noted an increased coagulability, and further that in obstructive jaundice the usual delayed coagulability was overcome. Too high a proportion of calcium delays coagulation. The use of calcium salts as local hemostatics is a failure.

In the clotting of milk by rennet, calcium is a necessity. (See Rennet.) However, if an alkaline calcium salt, such as in limewater, is added to milk, the alkalinity will check the rennet action and the milk will not coagulate. It is probable that, as a rule, any ordinary amount of lime-water is neutralized by the acid of the gastric juice, with the formation of calcium chloride.

Januschke (1910) has shown that pleural effusions may be checked by subcutaneous injection of calcium chloride, and Chiari found that transudation and edema were favored by the removal of calcium, which normally serves to check the permeability of the vessels. These experimenters and Meyer were able to check pleural effusion resulting from diphtheria toxin, and to reduce the conjunctival edema resulting from the application of irritants. Other authors have reported good results from the use of calcium salts in serum-sickness from diphtheria antitoxin, in angioneurotic edema, in chilblains, and in other conditions suggesting abnormal permeability of the vessels.

In the intestines calcium salts have been found to retard or check peristalsis, to lessen intestinal secretion, and to prevent the action of some of the cathartics.

In diabetes Kahn and Kahn obtained a fall in the sugar of the blood and urine by an intravenous of 1 to 3 1/2 ounces (15-50 c.c.) of a 1.4 per cent. solution of calcium chloride.

Calcium Poisoning

Large doses of the chloride intravenously at first increase the contractility of the heart, but soon bring about its stoppage in systole, the arteries being contracted and the pupils pin-point. From 50 c.c. of 1.4 per cent. solution intravenously, Kahn and Kahn noted great weakness, muscular pain, a fall in systolic and diastolic pressures, and in one case collapse and coma. Towles gave 5 drams (20 gm.) of the lactate daily by mouth for 15 days without toxic effects.

Therapeutics

Precipitated chalk is used largely for cleaning teeth. Prepared chalk is used as an antacid and in diarrheal conditions. Lime-water is used as an addition to milk to render it more palatable and more readily borne by the stomach, and to increase its calcium content for growing children. Lime-water has also been added to skin lotions for eczema and dermatitis.

Calcium chloride and calcium lactate have been employed - (a) In hemorrhagic conditions, with questionable results, as hemophilia, the purpuras, scurvy, the hemorrhages of typhoid fever and tuberculosis, melaena neonatorum, etc. They are not indicated unless the coagulability of the blood is distinctly reduced, (b) As preliminary to operations in obstructive jaundice. (c) In tetany and the nervous manifestations following parathyroidectomy or oxalic acid poisoning. (d) In nervous diseases with hyperexcitability, as epilepsy, chorea, spasmophilia, and the tics. (e) In serum sickness, urticaria, angioneurotic edema, chilblains, pleurisy with effusion, etc. (/) In bronchial asthma, to lessen nervous excitability and angioneurotic swelling of the bronchi. (g) In hay-fever to lessen the nerve irritability which leads to sneezing.

To gain any effect large doses must be administered daily. Either the lactate or chloride may be used in dose of 15 to 60 grains (1-4 gm.) three times a day. The bitter saline taste of the chloride may be masked by peppermint or lemonade. Hy-podermatically, a 4 per cent. solution may be employed. Intravenously, a 1 to 2 per cent. solution of the chloride may be given in amounts of 100 c.c., or a 0.2 per cent. solution of the lactate in normal saline in amounts up to 500 c.c. The chloride must not be confused with the antiseptic, chlorinated lime (chloride of lime).