Bromine

BROMINE, Bromum (from Greek bromos-stench), a liquid metalloid of the halogen group, with chemical symbol Br; atomic weight 79.92; it occupies the 35th place in the periodic system of elements, the 4th in group VII. A dark reddish-brown liquid, specific gravity 3.188 at 0°, only transmitting light in very thin layers; very volatile, at room temperature it turns into yellow-red heavy vapors with a strong suffocating odor. Liquid bromine produces severe burns on the skin and mucous membranes, healing slowly; upon cooling it solidifies into a crystalline mass with a melting point of -7.3°; boiling point +63°; it dissolves at +20° to 3.2 parts in 100 parts of water; at higher temperatures solubility is less, at lower temperatures solubility increases, and at -2° bromine gives a crystalline hydrate Br₂ + 10H₂O; in alcohol, chloroform, and carbon disulfide bromine dissolves very well. Bromine is not combustible, but some substances in it may ignite; bromine itself, possessing enormous chemical energy, even at ordinary temperatures combines without any expenditure of external energy even with such low-energy metals as copper and silver. In nature, free bromine is not found, but it is very widespread in compounds: it is found in sea water, in some mineral springs, in the Strassfurt mines, in Mexico and Chile. Bromine was discovered in 1826 by Balard from a mother liquor obtained after the extraction of common salt from sea water. In animal and human organisms bromine has been found many times, but it is still not decided whether this presence is accidental or whether bromine is a constant constituent of animal organisms. Bürgi considers that the most probable is that bromine enters the human organism exactly from outside; however, this is such a frequent and constant phenomenon that the presence of bromine in organs must be regarded as a normal phenomenon. Medical application of bromine began soon after its discovery; as early as 1828 it was used instead of iodine in syphilis, but without success. Since 1864 potassium bromide began to be used for insomnia (Henri Benrend) and with great success against epilepsy (Vigouroux); up to the present time, practitioners use bromide salts (K, Na, and NH₄) to reduce and weaken epileptic attacks or even sometimes to stop them as one of the most reliable methods of treating epilepsy. In this case, the action of the indicated salts is conditioned by the bromine ion; the difference in the influence of different bromide salts is based on the action of the cations entering them. It is not easy to experimentally determine the pharmacological properties of bromide salts on animals, just as on healthy people, but in patients the difference in the action of bromine compounds from chlorine is expressed vividly. Krosz was the first to experimentally determine the influence of bromine, and the increasing pharmacological action of bromine can be represented as follows: a locally irritating action of bromide salts (to a considerable extent dependent on the high osmotic pressure of the salt solutions, on the one hand, and on the speed of absorption of these salts on the other) occurs on the mucous membranes of the mouth, pharynx, and stomach; salivation increases, appetite and gastric motility, especially of an empty stomach, are enhanced; with large doses of bromine pains in the frontal sinuses appear; reflex excitability of the root of the tongue, palate, pharynx, and posterior wall of the pharynx from bromine is reduced or even disappears. Memory and clarity of thought fall, speech slows down; a feeling of fatigue easily appears; a state of rest conducive to sleep sets in; vision weakens somewhat, doubles and becomes blurred; hearing dulls, ataxia appears; heart contractions slow down; body temperature falls. The presented symptom complex is characteristic for acute bromine poisoning. The place of bromine's depressing action (according to Januschke) is first of all the sphere of the large brain, central apparatuses of will, consciousness, equilibrium, and muscular movements, and later the action of bromine spreads to the spinal and medulla oblongata; the peripheral sensory and motor nerve apparatuses, however, remain untouched. The metabolism in the use of bromide preparations is still not sufficiently elucidated (V. Schulze): the amount of urine increases, but there is no regularity in the excretion of nitrogen; the amount of sulfur increases somewhat and the excretion of phosphorus decreases, which gives the right to conclude about the changes occurring in the distribution of substances in the nervous system. However, the accuracy of these conclusions on the influence of bromide salts is hindered by the discrepancy with the results obtained by other authors in the study of the action of bromides. When bromide preparations are introduced into the organism, the distribution of bromine in it occurs unevenly; most bromine is found in the blood and especially in the blood cells; in the liver and kidneys only traces; in the brain bromine is very little: according to Büchner only 0.0266% (is found here in a soluble form, partly in lipoids, partly in lymph spaces or in the protoplasm of glia cells). There is no significant retention of bromine in the brain. In general, the amount of bromine deposited in the organism is in considerable dependence on the presence of chlorine in the organism: the poorer the organism is in chlorine, the more bromine is retained in it, bromine taking the place of chlorine, replacing it, among other things, in the contents of gastric juice, where therefore in such cases, instead of hydrochloric acid, hydrobromic acid is found. In therapeutic terms, this fact is used in such a way that for greater effectiveness of bromine in the treatment of the patient, a diet with reduced content of common salt is prescribed together with bromine (Januschke), and since chlorine, in turn, promotes the excretion of bromine, the physician requires the ability to regulate the amount of chlorine given with food. In acute and chronic bromine poisoning the patient is given large amounts of chlorine (common salt); however, the introduction of chlorides cannot eliminate the anesthesia that has set in in the poisoned person. A comparative study of the action of chlorine and bromine on the colloidal substance of the brain led Bernoulli to the conclusion that the brain substance swells more from bromine than from chlorine, and that chlorine, being in the brain both in the form of stable compounds and in the form of a more mobile compound, can be easily displaced by bromine. Organic bromine preparations, in which bromine is combined with substances of the fatty series, act like bromides, i.e., by the bromine ion. But if bromine is linked in a ring of the aromatic series, then bromine is not split off from such preparations, and the entire molecule acts actively. The introduction of bromine into compounds of the fatty and aromatic series significantly strengthens the action of narcotic and disinfecting substances, which is used to obtain ever new medicines. On the other hand, by synthesizing bromine organic compounds, one strives to obtain such preparations which, not decomposing in the stomach and not causing irritation of its mucous membrane, are absorbed intact in the stomach or intestine and, depositing in the tissues, act on the organism only later by splitting off bromine. Bromipin was the first preparation of this kind to enter medical practice. Bromobenzene and para-bromotoluene do not split off their bromine in the organism. Sabromin (dibromobenzoic acid with 30% bromine) deposits its bromine abundantly in the subcutaneous fat tissue and liver. Compounds of bromine with proteins also have therapeutic application, and Januschke considers that in these cases bromine acts in the organism either as an ion or as sodium bromide. The place of greatest excretion of bromine compounds from the organism is the kidneys; however, bromine is excreted in small amounts also by the intestine, mucous membranes, through the skin, and with milk. Excretion of bromine on the skin often leads to the appearance of various rashes on the skin: acne (especially abundant on the face), pustules, erythema, etc. These eruptions are characteristic for acute and chronic bromine poisoning (in so-called bromism). The signs of acute poisoning are indicated above; chronic bromism, however, is expressed by general emaciation, anemia, often a cachectic state, loss of appetite, catarrhal state of the mucous membranes of the eyelids, nose, pharynx, bronchi, and gastrointestinal tract, strong thirst, diarrhea, cooling of the extremities, skin rashes, weak pulse, difficulty of speech, weakening of mental activity, dullness, weakening of memory, lowering of pain sensitivity, general decline of strength. The phenomena of bromism are explained by the presence of large amounts of bromine, actively acting both at its place of location in the organism and on the paths of excretion. In bromism, relief is brought by a complete cessation of the use of bromine preparations, drinking a solution of NaCl or mineral water containing NaCl; the use of large amounts of milk, rinsing the mouth and pharynx with astringent solutions, maintaining the skin in the greatest possible cleanliness. In acute poisoning by bromine vapors, the patient is provided with breathing of pure air and is given to inhale water vapor with a small amount of ammonia.

In acute poisoning by bromine or its preparations taken internally, the patient's stomach is washed out with a 0.5% solution of hyposulfite of soda; starch paste, albumen water, alkaline drinks, milk of magnesia, and ice chips are given internally; burned areas are smeared with lanolin; subsequent treatment is as in chronic bromism. Pure bromine is no longer used therapeutically. However, bromine preparations, in the form of inorganic or organic compounds, play a large role in therapy: a) in epilepsy as agents that reduce and weaken attacks (sometimes even stopping them completely, at least for the duration of bromine treatment); bromides are administered in large quantities in these cases; b) against nervous excitement, hysteria, palpitations, insomnia, neuralgic pains, convulsive attacks of various origin; against nocturnal emissions, painful erections, incontinence of urine, vomiting in pregnancy, eclampsia in puerperae, chorea, alcoholism, delirium tremens, acute delirium, migraine, whooping cough, etc. Inorganic bromine preparations. Ammonium bromide, Ammonium bromatum (Ph. VII), NH₄Br, contains at least 79.9% bromine; white crystalline powder, odorless, salty taste; easily soluble in water, forming a neutral or slightly acidic solution; soluble in 10 parts of alcohol; easily changes on storage; volatilizes without residue upon calcination. The preparation possesses greater activity (Brown-Sequard) in pharmacological respects than other bromides. It is rarely used as such in therapy (single dose 0.5-1.0), since, decomposing rapidly in the body, it easily causes bromism symptoms; but it is often added in small quantities (0.05-0.1 per dose) to solutions of sodium bromide and potassium bromide. Potassium bromide, Kalium bromatum (Ph. VII), KBr, contains about 66.1% bromine; colorless or white lustrous cubic crystals, strongly salty taste, does not change in air; soluble in 1.7 parts water and in 200 parts alcohol. The aqueous solution has a neutral or weakly alkaline reaction. With internal administration of potassium bromide, slowing of the pulse and weakening of the heart's muscular activity are noted, which some authors relate to the action of the salt's cation, potassium. The maximum single dose is 4.0, in powders or solution; it is also used in pills, ointments, and for inhalations. Calcium bromide, Calcium bromatum, CaBr₂, white granular salt, odorless, sharp, bitter-salty taste; easily melts in the air; easily soluble in water and alcohol. It is stated that this salt has a particularly strong action in delirium tremens, insomnia, and mental fatigue. It is administered internally in solutions, in doses up to 1.0 per dose. Lithium bromide, Lithium bromatum (Ph. VII), LiBr, contains about 90% bromine; white, easily melting in air, crystalline powder, salty, slightly bitter taste, very easily soluble in water, easily in alcohol. It is usually administered internally in solutions, in doses of 0.2-0.5 per dose. Sodium bromide, Natrium bromatum (Ph. VII), NaBr, contains about 76.6% bromine; white, salty taste, odorless, hygroscopic powder; soluble in 1.2 parts water and in 16 parts alcohol, forming neutral solutions. In heart diseases, sodium bromide is used in therapy preferentially to potassium bromide; in other cases, the indications for use and dosage of sodium bromide are the same as for potassium bromide. Sodium bromide finds application in roentgenoscopy in urology. A 25% solution of it, introduced through a catheter into the renal pelvis, is a good (and harmless) contrast medium for roentgenoscopy of the pelves and the kidneys themselves.