Divison I. Class IV. Diuretics.

Diuretics are those agents which, acting on the kidneys, promote the secretion of urine. The renal secretion is one of the most important depurants in the body, removing in twenty-four hours, in health, from 600 to 700 grains of solid matter. This material is the product of the disintegration of the nitrogenized tissues of our bodies, and is so constituted that it can not be retained without producing disease. Such agents then, as will restore this secretion when diminished or suppressed, or that in certain states of the system will greatly increase it, can not but be regarded as among our most valuable means of removing disease.

The kidneys differ from all other secretory organs in being adapted to perform two entirely separate and distinct functions; this adaptation being manifested by their anatomical structure. These functions are the excretion or pumping off of the excess of water from the blood, and removing from the blood certain nitrogenized matters, the products of the waste of the tissues. The first merely relieves vascular turgescence, while the second is depurative, removing morbid matters from the blood.

The solids of the urine constituting its proper secretion, are urea, uric acid, creatine, creatinine, hippuric and lactic acid, and the soluble salts.

Urea forms the largest amount of the solids of the urine; 270 grains, or more than half an ounce, being excreted by a healthy adult in twenty-four hours. Its chemical formula is C₂, N₂, H₄, O₂. This is a highly nitrogenized compound, and constitutes the form under which a large quantity of nitrogen is expelled from the system. Urea is produced by the disintegration of the worn-out tissues of the body; it contains as much as five-sixths of the nitrogen taken into the body, and it constitutes the mode by which the largest portion of nitrogen is removed from the body. Dr. Golding Bird states, that "Its origin must be traced to the destructive assimilation of those tissues of the body which are removed to make room for new matter. Minute quantities of urea escape from the system by the skin, but this body is removed so rapidly from the blood by the kidneys, that very minute traces of it only can be obtained, unless these organs become diseased, and are then no longer fitted to perform their important functions of depuration."

The effects produced by the retention of this element in the blood, from defective secretion of the kidneys, is well shown by the experiments of Prevost and Dumas. They extirpated the kidneys of dogs; on the third day after the operation, vomiting commenced, there was diarrhea of a copious brown liquid, fever, with heat varying as high as 110°, and sometimes as low as 92°; pulse very small and frequent, breathing labored, death ensued from the fifth to the ninth day. After death there was found effusion of serum in the brain, copious mucus in the bronchia; the liver was inflamed, and the bladder much contracted; the blood was more watery than natural, and contained urea, five ounces of the blood of a dog yielding twenty grains of urea. The symptoms appearing in man from retention of urine are obstinate vomiting, diarrhea, typhoid symptoms, low muttering delirium, epileptic convulsions, coma, etc. All these effects, says Dr. Williams, may be traced to excrementitious matters being retained in the blood, especially urea, which has, in very many instances, been detected in considerable quantities—in the greatest amount acting on the system as a narcotic poison; in smaller, acting as an irritant, inducing low inflammations in various membranes and viscera; and in a still lower degree causing sundry functional disorders, fluxes and dropsies, impoverishing the blood, and inducing degeneration of certain textures.

Uric acid, creatine and creatinine, are substances similar to urea; that is, highly nitrogenized bodies. Like urea they are excrementitious substances, the product of the waste of the tissues; their amount is small compared with urea, but they are probably as deleterious to the system, according to their quantity, as that body. Hippuric acid is also a small constituent of the urine of man, and not always present. It differs from the others in containing but a small proportion of nitrogen, and is probably formed by the disintegration of the carbonaceous tissues.

From what has been stated above, it will readily be seen that this is one of the most important excretions of the body. Through the kidneys we have eliminated a large amount of the excrementitious materials formed by the disintegration of the nitrogenized tissues of the body; and it has been satisfactorily proved that the materials thus excreted, if retained, will act as a most virulent poison on the system. If this excretion is, then, so important in health, what must it be in disease, when disintegration of the tissues of the body is actively going on? And what benefit must be derived from such agents as will promote their elimination?

Action of Diuretics.—Diuretics are absorbed into the circulation, and act directly upon the secernent structure of the kidneys, as is evident from the reappearance of those substances in the urine. The same agents, if injected into the bloodvessels, will exert a similar influence upon the renal secretion. To those agents which increase the secretion of urine, whether taken into the stomach or absorbed from any other portion of the system, or injected into the veins, in suitable quantities, the term direct diuretics is appropriate, and to those agents it is frequently, and should be exclusively applied.

Other agents may exert an indirect influence over the urinary secretion, as diluents, by causing vascular repletion, and thereby causing an increased action of the kidneys to remove the water. Cold applied to the surfuce lessens the amouut of the cutaneous secretion, and thereby imposes an additional burden upon the kidneys, and when they are able to perform this function, increased diuresis follows. Cathartics sometimes greatly increase the amount of this secretion, by removing congestion of the kidneys, by producing revulsion to the bowels, etc. In consequence of these and other agents promoting diuresis by these indirect influences, they may be termed indirect diuretics.

Those agents only should be named diuretics, which act directly on the kidneys, and stimulate them to increaeed action, and not those which act on some other organ first, and subsequently exert an indirect influence on the kidneys.

Some of the direct diuretics merely increase the water of the urine, without a proportionate increase of the solid constituents; to these Dr. Golding Bird gives the name of renal hydragogues. Though this class of agents greatly increase the fluid portions of the urine, and thus diminish its specific gravity, yet it is found that the solids are increased, though not proportionately; the excess of water washing away but a small additional amount.

Others, having a direct chemical action upon the body, greatly increase the amount of the solids, either with or without a proportional increase of the entire amount of the urine. To these Dr. Bird gives the name of renal depurants.

In regard to the action of the renal hydragogues, Dr. Bird lays down the following proposition: "Remedies which exert no chemical action on organic matter out of the body, appear to be incapable of augmenting the quantity of solids in the urine, and hence are only of use in increasing the elimination of water—they may and do act as renal hydragogues, but not as renal depurants." In proof of this proposition, we may adduce the following table, calculated by Dr. Bird, from Krahmer's observations:

Renal depurants, though they generally increase the amount of urine passed, greatly increase the solid constituents of it. This they do, not only by stimulating the proper secretory apparatus of the kidney, but by increasing the metamorphosis of tissue within the body. The agents composing this class all exert a chemical influence upon dead animal matter, and when absorbed, they tend to break down all the imperfectly organized tissue, and by their direct action upon the kidneys they cause it to be excreted. This class of agents embraces the alkalies, the carbonates and their salts, with such acids as in the animal economy are capable of being converted into carbonic acid, including the acetates, citrates, and tartrates of soda and potassa. In regard to their action we may adduce the following example from Dr. Bird:

The reason why, probably, this class of diuretics is not held in greater repute by many practitioners is, that in fevers and other acute diseases, attended with increased metamorphosis of tissue, the vegetable hydragogue diuretics are administered instead of the true renal depurants. We are satisfied that this is the fact, and would call the attention of the reader especially to this latter class. In the diseases just named the worn-out and exhausted tissues, floating in the blood, become a constant source of disease; in many instances we may assume that it is the disease—they are, however, in such a condition as not to be readily excreted. Now, it is a well known fact, that the alkalies break up these into various secondary products, even without the body, and we may readily suppose that the change that takes place in the circulation is such as to fit the worn-out tissues for excretion.

Dr. Bird makes the following highly interesting observations upon the case given above, in which the acetate of potash was given, and upon the use of diuretics: he says, "The results of these analyses show that, after deducting the excess in the amount of soluble salts, arising from the conversion of acetate of potassa into carbonate in its transit from the stomach to the kidneys, the solids of the urine, separated from the blood under the influence of the chemical diuretics, exceeded those excreted without its aid by one hundred and ninety grains. We further learn that, although a large proportion of matter was metamorphosed into both uric acid and urea, after the administration of the acetate, still that the greatest increase was in that mixture of organic products set down as extractive, and which, as we have seen, consisted chiefly of creatine, creatinine, uroxanthin, and matter rich in sulphur. In the example adduced, not only did the patient lose an excess of thirty ounces of water in twenty-four hours, but she wasted to an extent of one hundred and ninety grains more than if no remedy had been given; and to this extent had the blood been depurated of those elements which yielded easiest to the influence of the alkaline salt. As it can not be denied, that vital force is ever active in opposing the chemical changes to which all living fibers are obnoxious, it is fair to assume that this resistance will increase with the vital endowments of a part; or, in other words, that the elements of our frames resist chemical influences in the ratio of their vitality; it would follow that such constituents of our bodies as present the greatest departure from health, are less highly vitalized, and thus would be expected to yield the easiest to the influence exerted by the alkaline diuretics, or renal depurants. As a result of this view, we should expect that when we cause an alkaline carbonate to circulate through the blood, it exerts an influence on the nascent elements of those matters less highly influenced by life, resembling that which it exerts on dead matter, aiding their resolution into substances allied to those produced out of the body, and actually causes the matter to assume so soluble a form as to allow of its ready excretion. This remarkable effect of the alkaline diuretics (although now demonstrated by actual experiment, and the results of their chemical influence detected in the stream by which they are washed from the body) was not overlooked by the observing physicians of former years. It was, indeed, acted upon by the old physicians—witness the host of apozems, diuretic decoctions, and diet-drinks, in which renal stimulants abound; and let us not shut our eyes to the success of the practice; for unless we deny all credence to the statements of the painstaking practitioners of past times, those who will read their quaint records of cases, will learn how generally they succeeded in curing the effects of a caco-aemia, an unhealthy blood, as evidenced in various eruptive affections, cellular membranous sores, furunculi, and very many such ailments. It is true, that in looking at some of their prescriptions we do not generally observe remedies which have now much confidence placed in them as trustworthy diuretics; but then an important element of their potions is, most undoubtedly, the water of the decoction employed, not in doses of tablespoonfuls, but as was common in former days, of pints. A most important truth here demands our attention. It may be said, that it is true that if a patient takes a pint or two extra of water he will, supposing that no organic lesion exists, excrete a large bulk of urine from the necessity there exists for pumping off the excess of diluent partaken of. In this way a pint or two of water becomes a diuretic: this every one's experience will enable him to admit; but what is this, it may be asked, but the mere drawing off of excess of water—where is the proof of blood-depuration? This proof is afforded by calculating the amount of solid constituents of the urine. It will then be found that the excess of water does not escape alone, but there is really washed away with it, a certain, although not very large, quantity of solid debris."

Therapeutic Indications.

I. Action in Febrile and Inflammatory Diseases.—In all febrile diseases, there exists generally a torpor of the excretory organs, and hence the metamorphosed tissues—the worn-out materials of the system—are not eliminated, but remain in the circulation. We have also mentioned the fact in a previous part of this work, that fever in a majority of cases is caused by, either the retention of an excretion, which acts as a foreign matter,—a ferment in the blood,—or by the introduction of such a material into the circulation from without. In either case the decaying matter while in the circulation, acts as a ferment, transmitting its decomposing tendencies to every portion of the blood that is not sufficiently vitalized to resist this chemical influence. If such is the case, and we believe it is well substantiated, we can plainly see the beneficial effects that would follow the use of such agents as would cause the elimination of an ounce and a quarter of this excrementitious matter every twenty-four hours.

Renal depuratives are then indicated in all febrile diseases, for their eliminative action. They not only stimulate the kidneys to normal action, removing such matetial as is already fitted for excretion, but by their chemical action while in the circulation, they so change the less vitalized portion of the circulating fluid that it is also excreted. The alkalies and their salts, which form the principal agents of this class, also act as refrigerants, lessening the heat of the body. When we wish to produce this effect, we administer a salt of some of the organic acids, the acetates, citrates, etc: this salt in its passage through the blood to the kidneys, is converted into a carbonate. In order to convert one equivalent of such a salt (for instance the acetate of potash), into a carbonate, eight equivalents of oxygen must combine with it. This oxygen, therefore, which is appropriated by the diuretic, is abstracted from the amount which would have acted upon the tissues of the body, and not only is there a less amount of heat generated, but there is also a marked decrease in the waste of the tissues, owing to the fact that the remedy has appropriated oxygen, which otherwise would have acted directly upon them. We have therefore four effects from such a salt: first, it stimulates the kidneys and causes an elimination of such material as may readily be excreted by them; second, it so changes those parts having a low degree of vitality that they are fit material for excretion; third, by appropriating oxygen to form a carbonate it proves refrigerant; and lastly, it diminishes the production of effete matters—the breaking down of the tissues by presenting their oxygenation.

In sthenic fevers they act as antiphlogistics, that is, according to many eminent authorities, they have the power of diminishing the amount of fibrine in the blood. Guliver has also noticed that they counteract the tendency of the blood-corpuscles to become aggregated in rows, a tendency especially observed in inflammation; and by diminishing the amount of the serum, they lessen vascular repletion.

In asthenic or typhoid fever, they indirectly increase the strength of the patient, by removing the materies morbi, which so depresses the vital powers, and especially the brain and nervous system; and may not the change which they effect in such material, even if it is not excreted, prevent its acting as a ferment in the blood?

Dr. Golding Bird states that he has found them of great value in remittent and intermittent fevers; though they are not antiperiodic, yet he believes they will effect that which quinine and its allies can not do. He says: "When to a person suffering from the effects of marsh malaria, acetate of potash has been administered to the extent of ʒij. in the course of twenty-four hours, largely diluted, and continued for two or three weeks; not only is no injury effected by the remedy, but the most marked benefits are observed to result. The patient's skin becomes less dusky, the expression more healthy, the dull aspect of the eyes changed for one of cheerfulness, the engorgement of liver and spleen lessens, and the paroxysms of 'dumb ague' disappear."

The vegetable hydragogue diuretics are also useful in these diseases, and especially is this the case when they are given in infusion or decoction. The diuretic agent stimulates the kidneys to remove the serum of the blood, and thus the vessels are depleted, while the water of the decoction or infusion acts as a depurant, washing away some of the detritus of the system. They are, however, comparatively unimportant agents, in these diseases, so far as their diuretic properties are concerned; but many of them exert other influences upon the system, which may be beneficial.

II. Action in Rheumatism.—The class of diuretics termed renal depurants, are among our most valuable agents in the treatment of rheumatism. In several instances we have witnessed the beneficial action of the acetate, or nitrate of potassa, in these cases, with surprise. We have seen the severe symptoms disappear in twenty-four hours, and in a few days the patients would be well. This, however, is not invariably the case; for we have also known instances where, unless they were combined with other agents, they produced no effect. In such cases, however, a combination that will effect both the cutaneous and renal excretions, as the combination named under the head of diaphoretics (eupatorium perfoliatum, asclepias tuberosa, sanguinaria canadensis and nitrate of potassa), we have never known to fail, if properly carried out.

Dr. Golding Bird strongly recommends the acetate of potassa in this disease; and the success of his treatment, in the wards of the London Hospital, would go to prove that he has not overestimated its value. In regard to its use, he says: "I would not willingly use language which was not completely compatible with experience; but I do not still hesitate to declare that I have never seen the disease in question yield with so much facility to any other remedy. In the severest cases which have been admitted into the hospital under my care (and I prefer alluding to them rather than to cases in private practice, as they have the advantage of being watched by many, and less chance of error arising in the reports of the progress of the patients), I have seen the cure to be more rapid, and the immediate relief to the patient more marked by the use of the acetate of potassa, in quantities of half an ounce, administered, largely diluted, in divided doses, in twenty-four hours, than by any other treatment. In three days I have repeatedly found the exquisite pain of the joints nearly absent, the patient comparatively comfortable, and able to bear with greater ease the helpless state in which the still swollen joints place him. In no case has any ill effect followed the use of the remedy, and while the cure has been far more expeditious, the ill effects of colchicum and mercury have been avoided. The pain remarkably and suddenly lessens, as soon as the urine becomes alkaline, and rises in specific gravity."

In chronic rheumatism, these agents are also very valuable. Whenever they produce a marked increase of the solids of the urine, the disease yields to their use. The beneficial effects of the iodide of potassium, is, probably, due to a greater extent than is supposed, to the diuretic properties of this salt. In two cases particularly noticed by us, where this agent proved beneficial, it acted as a diuretic, the solids of the urine being much increased; and in other cases we have derived similar benefit from other salts of potassa.

III. Action in Chronic Diseases.—In chronic disease, where there is evidence of an unhealthy state of the blood, the class of renal depurants will be found highly beneficial. They may be truly called alteratives in many cases; that is, they remove the vitiated materials circulating in the blood, and thus promote digestion, assimilation and nutrition. We have seen the habitually coated tongue, the sallow skin, cutaneous eruptions, foul stomach, etc., disappear under their use, when tonics and restoratives had proved of no avail. And may we not ask, is not the beneficial effect of our compound sirup of stillingia and iodide of potassium, so frequently used in such cases, partly due to their acting as renal depurants? We have noticed under their employment an increased amount of the solids of the urine, which would tend to prove it.

IV. Action in Dropsy.—As we have already given a some what extended account of the action of diuretics in this dis ease, under the head of cathartics, a short notice will suffic here. The class of diuretics principally used in dropsy a those termed renal hydragogues, or those that increase the fluid portions of the urine: of these some are topical stimulants to the kidneys, others to the entire system, while still another class are sedatives. They prove curative in two ways: first, by removing the serum of the blood, and second, by their derivative influence.

All diuretics decrease the fluid portions of the blood, and thus they not only leseen the amount of fluid circulating in the vessels, but they also destroy the balance existing between the solids and fluids of the blood. We have already referred to the law that when a portion of the circulating fluid was abstracted, absorption through the veins became active, in order to replace the amount so removed. If no fluids are ingested to replenish this loss, absorption will take place from any fluid that has been effused; and this dropsical effusion will be taken to supply the amount of serum abstracted.

Undoubtedly much advantage is often secured by the derivative influence of diuretics, particularly those of an exciting character. They stimulate the kidneys to increased activity, and render these organs the center of fluxion to which the circulating fluids are directed in increased quantities, and from which the serum is abstracted by the increased activity of these organs. While this local derivative action continues the vessels implicated in the diseased action, and from which the serous exhalation or dropsical effusion is taking place, are relieved of their burden, and allowed an opportunity of recovering their tone. This point is no longe the center of fluxion, or, at least, it is only so in a diminished degree; consequently, the effusion ceases, or becomes diminished in proportion to the action of the renal stimulant.

The sedative diuretics are indicated in sthenic habits, or whenever there is dropsical effusion attended with vascular activity; they are contraindicated when the habit is asthenic, as when the dropsy is of a passive character, the stimulant diuretics are required.

It must be borne in mind that hydragogue cathartics are of primary importance in all cases of dropsy, while diuretics are but secondary, though important: and this is especially true in dropsies arising from indurations or visceral engorgements of any kind. In such cases hydragogue and deobstruent cathartics are not only important therapeutic agents, but they are indispensable to success.

V. Action in Diseases of the Urinary Organs.—In diseases of the urinary organs they become the most efficient agents at our command. In acute inflammation of any portion of the urinary apparatus, refrigerant and demulcent diuretics are of the first importance; they increase the quantity of the urine, and being excreted with it, they lessen its acrid character, and lessen its irritant action upon the inflamed tissues. In chronic inflammation, catarrhal affections, or in cases of ulceration of the mucous membrane of the urinary passages, the balsamic diuretics are demanded; these agents probably act as direct local stimulants, and by the new action which they set up, the morbid process is relieved. The tonic and astringent diuretics, as the uva ursi, pipsissewa, buchu, etc., often prove highly valuable in the same cases. They are also used in diabetes, in conjunction with other agents, with decided advantage. The same class of agents are often employed in combination with the mineral acids, in cases of phospbatic deposits, and with alkalies in cases where the lithates are in excess. In these diseases they seem to act by medicating the urine, which comes in direct contact with the diseased tissue, and in this way they act as topical remedies. The balsam of copaiba, cubebs, etc., probably owe a portion of their virtue in the cure of gonorrhea to their impregnating the urine with their medicinal properties, and being thus brought into direct contact with the inflamed mucous surface.

Recapitulation.

1st. Diuretics are useful in any disease in which there is a diminution or suppression of urine; in such cases they stimulate the kidneys to normal action, and thus promote the elimination of the normal constituents of the urine.

2d. A certain class of them greatly increase the solids of the urine, not only by causing an elimination of such materials as are already fitted for excretion, but also, as we suppose, by so changing the less vitalized material as to permit its elimination.

3d. The alkaline diuretics not only increase the solids of the urine, and thus prove eliminative, but they also act as refrigerants, and to some degree prevent the disintegration of the tissues of the body, by combining with a portion of the oxygen in the circulation.

4th. They promote the absorption of dropsical effusions, by lessening the quantity of the circulating fluid, and by destroying the balance between the solids and fluids of the blood—absorption being active in proportion to the diminution of serum in the vessels.

5th. They act as counter-irritants, causing the formation of a new point of excitement and fluxion, by which means other parts are relieved.

6th. They act topically in diseases of the urinary organs; their virtues being in part transmitted to the urine, they are brought into direct contact with the diseased tissue.

7th. They augment the elimination of water, and thus enable the urine to hold in suspension any material requiring much of this fluid to hold it in solution. They also act as solvents in calculous affections; but most probably this is only in proportion to the amount of water excreted—water, according to the best authorities, being the best solvent "stone."

The American Eclectic Materia Medica and Therapeutics, 1898, was written by John M. Scudder, M.D.