ON THE ACTION OF ALTERATIVES.

(The Practitioner' for September 1876.)

IF we were to take the word alterative in its widest sense, it would embrace all the medicines we employ; for all of them are used for the purpose of producing some alteration or other in the bodies of those to whom they are administered. Nor is the alteration confined to them alone; it may also influence their offspring, and Buchheim very truly says that we are quite justified in calculating what the influence of a purgative, which we take to-day, will be upon the bodily and mental well-being of our great-grandchildren. I know a lady who believes that ill-temper in children is due to illness, and whenever any one of her own. family was naughty during their childhood, she invariably administered a dose of Gregory's mixture to the offender. The practice was most successful, mind and body were purged together, the ill-temper fled with the evacuation of the bowels, and a wholesome dread lest the dose should be repeated co-operated with its physical action to prevent a return of the naughty fit. Who shall say that the temper and disposition as well as the bodily health of this lady's children and grandchildren are not altered for the better by her judicious use of rhubarb and magnesia, and who shall deny to Gregory's mixture an honourable place among the alteratives? And yet if we saw its name appearing in a list of them we would be very apt to say that it was like Saul among the prophets-it had a perfect right to be there, but it would have been better elsewhere-Epsom salts, jalap, and other purgatives being more suitable companions for it than iodide of potassium, arsenic, and the other remedies to which we usually give the name of alteratives. For custom has now excluded from this class all medicines which give external signs of vigorous action by purgation, sweating, or diuresis, and has restricted the term to such remedies as do their work slowly

and secretly but none the less effectually. In short, we use the word alteratives very much as a cloak for our ignorance. For example, a patient comes to us complaining of more or less constant headache just above the eyebrows. We generally associate such frontal headache with disturbances in the digestive apparatus, and we accordingly at once inquire into the condition of the tongue, appetite, and bowels. We find that the tongue is fairly clean, the appetite fairly good, but the bowels are constipated. We give a drachm of sulphate of magnesia three times a day, get the bowels to act properly, and in four cases out of five the headache disappears. But in the fifth case it remains, although the constipation has been removed and the evacuations are free. We order the medicine to be continued, but in addition give a calomel and rhubarb, or a blue pill at night, and now we obtain the desired effect. The sulphate of magnesia alone was unable to remove the cause of the headache, but the mercury seems to touch the right spot and put things in proper order again, so that no farther pain may be experienced for a good while to come.

What the probable reason of this is I will mention by and by, but at present I wish to contrast the action of these two remedies with that of a third.

Suppose, then, that we see, as we very often do, a patient complaining of pain above the eyebrows but with all the functions. of the alimentary canal apparently in good order. These cases are frequently met with amongst girls from fourteen to twenty. The tongue is fairly clean and moist, although it may be slightly marked with the teeth at the edges, there is no complaint of wind in the stomach, there may be no pain after eating, and the bowels may be quite regular. We order them ten minims of dilute nitro-hydrochloric acid before meals and the pain disappears, just as it did in the other cases after salts or calomel. But here we have no sign of action produced by our remedy except the disappearance of the patient's complaint. There is no purgation. by which to explain the results: we cannot say that the morbid matter which caused the pain has been forcibly removed from the alimentary canal or from the blood. Our remedy has corrected the nutrition of the body in some mysterious and secret way, as mysterious and secret as the manner in which a hearty meal sustains the nutrition, and we class our medicine among the alteratives just as we class the substances composing the meal among the nutritives.

Or let us take another example. The skin, which ought to be soft and uniform in colour and smooth on the surface, becomes covered with round reddish spots, on which the epidermis accumulates, giving them a somewhat silvery hue, and from which it falls in scales. We give arsenic internally, and even without the use of any local application to the skin, although these are undoubtedly useful, we may find the scales fall off, the reddened spots disappear and the skin assume its normal appearance.

Here again our medicine acts in the same slow, secret way, causing the skin once more to return to its proper healthy mode of utrition, or, in other words, causing the cells which compose it to take up, assimilate, and use in the proper way the nutritive, materials brought to it.

Now I find the question, How do alteratives act? to be an extremely difficult one; and I do not feel at all certain that I shall be able to give the correct answer to it. But the difficulty of the question is not merely personal-it has been felt by every writer of a textbook on Materia Medica; and on looking through the standard works on the subject I see that an explanation of the mode of action of alteratives is rarely or never attempted.

I have, therefore, less delicacy in bringing the subject under notice, as my attempt to explain their action, even though incorrectly, may, by awaking criticism, and directing general thought to this question, lead some to a better solution of it than the one at which I have arrived.

We have already seen that there is a striking resemblance between nutritives and alteratives in the quietness with which they effect their purpose; and I believe that it will greatly assist our comprehension of the mode of action of those remedies which alter nutrition if we first take a glance at the way in which nutrition is normally maintained. A railway navvy, working with pickaxe, shovel, and barrow, striking hard into the firm earth or the solid rock, lifting heavy weights and wheeling heavy loads, violently exerting every muscle in his body and perspiring at every pore, would soon exhaust both his muscles and glands, if he were to abstain entirely from food and drink, and not replace the solid matter and liquids which he is continually losing while at work. He would get thinner and weaker, and would quickly die; while if he has an abundant supply of bread and butter, beefsteak and salt, with as much water as he wants, he may go on working day after day, week after week, and month after month, without his

strength undergoing the least diminution or his body becoming lighter by even a single ounce. It may be remarked that I have put salt here in the list of foods, and I draw special attention to it, because the quantity of it which we use is so much less than that of the other sorts of food that we are apt to forget it. And all the more so because we get it added to our bread by the baker, or to our butter by the dairyman, or get it thrown on our beefsteak while it is cooking, and thus forget that we may take a good deal during the day although we never put a particle of it on our plates during meals. And yet the simple experiment which we find in every boy's book of chemical tricks, of telling into which basin of water a hand has been put by the turbidity which occurs on testing it with nitrate of silver, shows how constantly we are losing salt from the skin; and if we put our tongue to our hand after we have been perspiring freely, the taste will convince us that the quantity of salt we lose by the skin is not inconsiderable, even if we were to leave out of account the much greater loss which takes place by the urine. We find no difficulty in understanding how the salt lost by the various emunctories is replaced by that which we take into our stomach. For salt dissolves readily in water, and when in a state of solution it diffuses easily through animal membranes. Thus when it is taken into the stomach it is soon. dissolved by the liquids it finds there, is absorbed into the bloodvessels, and travels with the blood to all parts of the body.

But with regard to the bread, butter, and beefsteak the matter is not so easy. It is true that fats may be made to pass through animal membranes, but not very easily, and the difficulty is greater when the membranes are moist, as they are in the body. Starch, of which the bread is composed, and albuminous substances, such as those of the beefsteak, hardly pass at all, and in order to be made available for the wants of the body, they must first be rendered soluble. Nor is this all. In order to render them 'soluble they must undergo a chemical change, the starch of the bread being converted into grape sugar, the myosin of the beefsteak into soluble albumen and peptones, and the butter being partially split up into fatty acids and glycerine. Now all these changes can be effected by the chemist in his laboratory, or by the manufacturer in his factory, but both of them require to use much force in the shape of heat to pull apart the atoms of the starch, albumen, or fat, and allow them to enter into new combinations. Thus starch is converted commercially into grape sugar by boiling

it with sulphuric acid; albumen into peptone, not by simply boiling it, but by boiling it under pressure in a Papin's digester with dilute hydrochloric acid; and fat is split up into fatty acid and glycerine by treating it with superheated steam. But the processes which require so much expenditure of heat-heat which might drive a railway-engine or a steam-hammer-are all carried on within the body at a gentle temperature by means of certain ferments. These ferments possess the wonderful power of doing, without any apparent effort, the same work of decomposing bodies, as only a considerable heat could do without them. In fact we might compare them to such things as nitro-glycerine, of which a small quantity will shiver into fragments a solid rock on which many and heavy blows of a powerful steam-hammer would have made but a slight impression. The ferments in the alimentary canal are pepsine, the pancreatic ferments, and the ferments of the intestinal juice. Pepsine differs from the other two in only acting in an acid solution, while the others act in neutral or alkaline ones, and this I consider to be a very important difference indeed, as you will presently see.

Although these ferments split up starch and albumen with such force, they do not seem to be used up in doing so, and a very small quantity of ferment will go on for a long time without seeming to be exhausted by its work. Now no manufacturer would ever think of throwing away anything with such valuable properties as this, and yet we used to imagine that nature improvidently threw them away, and allowed them to be excreted by the fæces. Some time. ago, however, it was found by Brücke that the whole of the pepsine was not voided in this way, for part of it was absorbed, and could be detected in the muscles and in the urine. Von Wittich also found a ferment in the liver and bile, which, like that of the pancreas, would convert starch or glycogen into sugar; and Hüfner found ferments which also possessed, like that of the pancreas, the double power of digesting fibrine, and converting starch into sugar in the lungs. From these facts I ventured some time ago, in a paper on the Action of Purgative Medicines, which I published in the Practitioner, to advance the hypothesis that the digestive ferments were reabsorbed from the intestinal canal, and being again carried by the blood to their respective glands, did duty over and over again. For if bile is either injected into the intestine or injected under the skin, it passes to the liver and is excreted by it; urea injected into the blool goes to the kidneys, and thus it