This section is from the book "A Text-Book Of Pharmacology, Therapeutics And Materia Medica", by T. Lauder Brunton. Also available from Amazon: A text-book of pharmacology, therapeutics and materia medica.
These are remedies which improve the nutrition of the body without exerting any very perceptible action on individual organs. The chief alteratives are :Arsenic.
Action. - Healthy nutrition depends (1) upon a proper supply of oxygen and nutriment to each tissue and organ in the body, (2) on the proper amount and kind of tissue-change in the various cells; (3) on the proper removal of waste.
The proper supply of oxygen and of nutriment to the body generally will depend upon the state of the respiratory and digestive organs; their proper supply to the tissues, as well as the removal of waste from them, will depend upon the circulation; and the removal of waste from the body generally will depend upon the bowels, skin, and kidneys.
The drugs which act upon the different organs just mentioned are considered under other headings, but the changes which take place in the tissues themselves appear to be effected by drugs which produce no marked corresponding changes in assimilation, circulation, or excretion. It is uncertain how they act: it is possible that they may alter in some way the action of enzymes in the body, but it is also possible that they act by replacing the normal constituents of the tissues and forming compounds which tend to break up in a different way from those which are ordinarily present.
Thus chloride of sodium and nitrogenous bodies such as albumen are amongst the most important constituents of the body; and we find that among the chief alteratives are substances which will replace chlorine, sodium, or nitrogen in many compounds. Thus we have iodine and iodides, and nitric or nitro-hydrochloric acids, which will displace or replace chlorine. We have chlorine itself, and chlorides which may alter the proportion of chlorides to other salts in the blood and tissues, and thus modify the solubility of various constituents of the tissues. We have salts of potassium and calcium, which may replace those of sodium; sulphur, and sulphides which may replace oxygen; phosphorus, hypophosphites, antimony and arsenic, which may replace nitrogen; mercury and its salts, which may replace calcium.
Besides these we have organic alteratives, regarding the action of which we can at present form no hypothesis unless they influence the processes of digestion. Nitro-hydrochloric acids, taraxacum, and small doses of mercurials, probably act either by modifying the digestion of food in the duodenum and jejunum, or by modifying the changes which it undergoes in the liver after absorption.
The action of drugs upon tissue-change has usually been investigated by ascertaining the amount of urea excreted before, during, and after the administration of a drug. Most of the older experiments on this subject are of little or no value, as sufficient care was not taken to ensure that the amount of nitrogenous food consumed each day during the experiment was exactly the same. As all the nitrogen taken in the food reappears in the urine, any irregularity in the quantity introduced into the body will cause a corresponding irregularity in the quantity excreted. After this fact was ascertained, the plan adopted by some experimenters was to deprive an animal of food for several days, until the excretion of urea due to the gradual destruction of its nitrogenous tissues became nearly constant. The plan now adopted is to give to a dog or a man a quantity of food of a uniform quality and the amount of nitrogen in which is exactly known. The quantity given each day is exactly weighed. The same amount of nitrogen is thus introduced into the organism every day, and therefore any variations in the amount of nitrogen excreted must be due to changes in the organism itself.
Observations on the excretion of urea only give us a very partial and imperfect knowledge of the process of tissue-change, and they ought to be combined, as in the experiments of Pettenkofer and Voit, with observations on the amount of oxygen absorbed and of carbonic acid given off. Such experiments as these, although very valuable, are very laborious, and comparatively few have hitherto been made.1
From experiments made with those necessary precautions just described it has been found that free consumption of water increases tissue-change very considerably, as is shown by the increased excretion of urea.
Common salt, sulphate of sodium, phosphate of sodium, acetate of sodium, borax, nitrate of potassium, chloride of ammonium, carbonate of ammonium, and probably all salts which pass out in the urine carrying water with them, somewhat increase tissue-change and the amount of urea excreted. Fats and fatty acids apparently lessen the decomposition of albuminous tissues and the excretion of urea, but glycerine has no action of this sort. Alcohol in small or moderate doses lessens, in large doses increases, tissue-change. Benzoic acid, salicylic acid, and benzamide, all increase tissue-change. Contrary to what perhaps might have been expected, tea, coffee, and cocoa have no action whatever on the excretion of urea.2 The experiments which seemed to show that they diminished it, appear to have been made without the necessary precautions. Morphine slightly diminishes the excretion of urea, but its action is much more marked on the consumption of oxygen and excretion of carbonic acid. These are greatly increased in the stage of excitement, and greatly diminished in the stage of quiescence. It would appear that these changes are not due to the direct action of the morphine, but only to the alterations of muscular activity which follow its administration.
1 A complete account of the whole subject is given by Voit in Hermann's Handb. d. physiol., Band VI. Theil i. This contains also complete references to the literature.
2 Voit, op. cit.
Quinine lessens tissue-change, iron appears to increase it, mercury also slightly increases it,1 while iodine appears to have little influence upon the quantity of urea excreted. This fact is of itself, I think, sufficient to show that the mere estimation of the quantity of urea excreted before and after the administration of a drug is quite insufficient to give us any precise information regarding its action on tissue-metamorphosis.
Antimony, arsenic, and phosphorus have a special action on tissue-change, and powerfully affect the glandular, nervous, respiratory, and cutaneous systems. In large quantities they affect the liver very markedly, producing fatty degeneration; and this also occurs in other tissues.
This fatty degeneration is due to a twofold action: - 1st, increased tissue-metamorphosis; and 2nd, diminished oxidation. In the normal condition albuminous tissues split up as indicated below: -
split up into
Non-nitrogenous substances. .
e.g. Fat, etc.
converted in health into
Carbonic acid, excreted by lungs.
e.g. Leucin, Tyrosin, etc.
Urea, excreted by kidneys.
In poisoning by antimony, arsenic, and phosphorus, the nitrogenous products of tissue-waste appear in much larger quantity in the urine than normally, owing to the increased decomposition which is going on. They may appear in the urine in the form of an excessive quantity of urea, as in cases of phosphorus-poisoning in the dog, but in man they may appear in the form of leucin and tyrosin. Owing to the diminished oxidation the non-nitrogenous substances remain in the body as fat, instead of being oxidised and passing out of the body as carbonic acid.
The exact nature of their effect on the nervous system has not been made out. Their action on the skin and epithelial cells of the lungs seems to be that of causing fatty degeneration.
Fatty degeneration of the liver occurs also in poisoning by salts of silver.
Mercury has a peculiar power of breaking up newly deposited fibrin and of causing disorganisation of syphilitic deposits. Iodine, iodides, and probably also chlorides, appear to act on the lymphatic system and promote absorption : their action is specially well-marked in cases of glandular enlargement.
Uses. - In general malnutrition without definite symptoms, mercurials, taraxacum, and nitro-hydrochloric acid are used and are especially indicated where the liver is suspected to be in fault, as where there are symptoms of biliousness, and also where oxalates and urates are found abundantly in the urine.
1 Boeck, quoted by Voit, op. cit.
In gout, salts of potassium and colchicum are used. Phosphorus and arsenic are employed in nervous debility : and they, as well as antimony, are serviceable in neuralgia, chorea, and other nervous diseases.
In diseases of the skin, arsenic is chiefly employed.
In diseases of the respiratory organs, antimony is very serviceable when the attack is acute; and arsenic is most valuable in some chronic conditions, especially in chronic consolidation, where it probably acts by producing fatty degeneration and softening of the effusion, so that it is either absorbed or expectorated.
Mercury is employed specially to break up deposits of lymph and to prevent adhesions, as in iritis and pericarditis; and is also used and is most serviceable in the treatment of syphilis. It is most generally employed in the secondary stage of this disease : in the third stage it is either given along with, or entirely replaced by the use of, iodides.