modify the action of medicines, and so it is proper to prescribe smaller and more guarded doses of remedies when treating them.

3. Age. Medicines behave very differently at the various epochs of life. Children and old people bear mercury well; in the case of the first, salivation is rarely, if ever, produced. Children, again, tolerate belladonna remarkably well, and so with many other remedies. On the other hand, opium is singularly obnoxious to children; two and a half drops of laudanum have killed a baby of three days old, three drops a strong child of fourteen months, and four drops a child of a few weeks. (Christison.) In infancy and childhood, blisters and vesicants in general produce most unpleasant consequences, and may even give rise to considerable sloughing and gangrene when kept for some time in contact with the skin. As is indicated below, treating by these remedies must be restricted to adults, and avoided even among these when there is much emaciation and the vitality is low. Again, leeches should be avoided in children, as they produce far too profound an effect-an effect, also, apparently out of proportion to the quantity of blood withdrawn.

4. Temperament and Diathesis influence the operation of medicinal agents. The sanguine and sanguineo-nervous temperaments bear depletory treatment much better than do the nervous and lymphatic. They are also more easily brought under the influence of stimulants, and hence need smaller doses. Opium, according to the opinion of some practitioners, is better borne by the melancholic than by the sanguine, and furthermore acts more beneficially upon them. Cathartics act very differently on various temperaments; upon the sanguine, small doses of the milder preparations produce ample movement of the bowels, whereas the phlegmatic, who by the way are commonly constipated, require very large and often repeated doses of the strongest drugs before the torpor of their bowels is overcome.

5. Habits and Mode of Life.-Exposure to vicissitudes, to roughing it, deadens the sensibility, while habits of luxury, indolence and ease tend to produce undue nervous sensibility. Persons of the first class reveal a sluggish reaction toward medicines, while those of the second are often profoundly affected by excitants, depressants and other groups of medicaments. The avocations of persons also largely modify the influence of drugs. Town dwellers, factory hands, workers in hot, ill-ventilated rooms are, as a rule, anæmic, and show little resistive power against the attacks of disease. In such persons diseases are apt to run an asthenic course, and all depletory measures produce profound depression, and are hence dangerous. In contrast to such individuals we have the dwellers in rural districts, the openair workers, and those who, well-fed and housed, lead out-of-door lives; in these classes we find disease pursuing a sthenic course,

while medicines to effect any marked influence need to be given in large doses, the most active drugs being called into requisition. All persons, however, when allowed to take drugs for a long time continuously, grow habituated. This habituation brings about a toleration in the individual, so that the drug no longer produces any apparent effect. Thus the habitual indulgence in cathartics leads to increased torpidity of the bowels, necessitating increasing doses, until at length the most vigorous purgatives, even in very large doses, cease to cause action of the bowels. In like manner, opium, morphine, chloral, rapidly grow into habits, increasing doses becoming requisite before sleep is attained. De Quincey's well-known case has unhappily been many times exceeded: a quantity of crude opium swallowed such as would serve to kill many individuals has been taken, with only the result of inducing opium dreams. Habituation to stimulants is again a further example. In the fevers of heavy drinkers enormous quantities of stimulants are needed before the heart is steadied or the pulse affected. Cocaine, itself of recent introduction, has already attracted habitués, and these unhappy creatures become as lost to self-respect and self-control as alcoholics or opium-eaters. The knowledge that this habituation occurs enables the practical therapeutist to keep his patient under the influence of a particular drug by the simple expedient of ordering intermissions in its administrations. It should be carefully remembered that upon returning to the use of the drug it is essential that the dose should be not that given at the end of the period of taking the medicine, but rather the initial dose, or some slight advance upon this. Again, when it is desired to give large doses of medicine to a person intolerant of its use, the end can frequently be attained by commencing with small doses, and rapidly increasing the dose until the desired quantity is tolerated by the patient.

Arsenic, among the inhabitants of Styria, is, as is well known, consumed in very considerable quantities, the habitués commencing with small doses and rapidly increasing the amount taken daily.

6. Race unquestionably exercises a modifying influence. Among the tribes of India, all depressants are very badly borne. Again, the dwellers in northern climes differ considerably from those who reside further south.

Among conditions unconnected with the individual we may notice

a. Combinations which Modify the Action of Remedies.—It often happens that two or more members of a particular class of medicines will, when combined, act more efficiently than either is capable of if exhibited alone. When it is assured that such a combination can be brought about, the blending is useful,

but every care must be taken to avoid linking together medicines which, even if chemically compatible, are nevertheless therapeutically antagonistic. The behavior of such a compound must be most prejudicial, as the use of really appropriate remedies may be stultified by commingling them with substances which abrogate their activity or lessen it to a minimum.

b. Combination of Medicines Chemically Incompatible.-As a general rule, it is inadvisable to prescribe in the same formula ingredients which are chemically incompatible, unless the resulting compound be the one which the practitioner wishes to administer; thus, if the citrate of potash is to be given, it may effectually be done, by giving, in one draught, citric acid and the carbonate of potash in solution; these mutually decompose each other; the carbonic acid is evolved, and the citrate of potash is obtained. It does not necessarily follow that, because the ingredients are chemically incompatible, the resulting compound is rendered inert; on the contrary, it may happen that it is much more violent in its operation than either of the ingredients used in its formation. Here we have to call chemistry to our aid, in order thoroughly to understand the changes which take place, and to ascertain what the compound resulting from the mixture is. Having ascertained this point, the next thing is to find out with what medicinal properties it is endowed. Many unchemical combinations are highly useful and valuable-e.g., yellow wash, a compound resulting from a mixture of corrosive sublimate and lime water; black wash, that of calomel and lime water; and the mistura ferri co., in which the carbonate of potash and the sulphate of iron are mutually decomposed, a simple carbonate of iron and the sulphate of potash resulting. But of all unchemical combinations, perhaps the most signally used is that of opium and the acetate of lead. These agents react chemically on each other, and produce the acetate of morphine and meconate of lead; yet experience proves the combination to be one of the highest value in hemorrhage and various diseases.

It must be remembered, also, that it often happens that when so-called chemical incompatibles are combined in a medicine, the resulting double decomposition liberates bodies which, from being freshly formed-nascent-possess peculiar activities.

It would be impossible to indicate in this place the very numerous cases in which substances are held to be incompatible. Chemical incompatibility is not in all cases an insuperable objection to their being blended as indicated above, but there are many mineral preparations which it would either be dangerous or useless to combine-e. g., calomel with alkaline chlorides, lest corrosive sublimate is formed, acids with alkalies, strychnine salts with spirits of chloroform, and so on. There are other forms of incompatibility—namely, what we may call pharma

ceutical; in such the mischief arising is, that unsightly although useful mixtures are formed-e.g., those containing iron and a vegetable preparation in which tannin exists, and mixtures incompatible with the secretions of the body, such as large doses of alkalies given during a meal; of these we shall treat under the heading of the best time when to administer medicine.

c. The Regulation of the Dose.-Almost every drug operates differently when given in a small and in a large dose. Tartar emetic, for example, in doses of from to of a grain, acts as a diaphoretic and expectorant; in doses of from to of a grain, as a nauseant; and if carried to the extent of two or three grains, it proves powerfully emetic. A very similar series of effects is produced by graduated doses of ipecacuanha; indeed, various observations tend to show that this drug in very small doses acts as a powerful anti-emetic. The neutral salts are aperient in large doses, and diuretic in small ones; opium acts as a stimulant in small, and as a narcotic in large, doses; and the oil of turpentine, in doses of one to two drachms, is an acrid irritant to the kidneys and genito-urinary organs, whilst in doses of an ounce, especially if combined with castor oil, it operates freely on the bowels, without producing any renal or vesical irritation. These are but a few examples out of many which might be quoted; but it may be observed, generally, that most of the medicinal substances whose operation is mild and beneficial in small doses may be converted into powerful poisons by being administered in large quantities.

The familiar names for doses, such as drop, teaspoonful, and so on, are, of course, wholly unscientific, and are likely to mislead unless used with much caution. In the case of drop, we find that while forty-five drops of water go to a drachm, one hundred and thirty-two of the tincture of the perchloride of iron are needed, and as many as one hundred and fifty of sulphuric ether, to fill the drachm measure.

Although useful, posological tables cannot be accepted as in-. fallible guides about doses. Each individual has his own dose, and the skilled therapeutist must, to be successful, acquire the art of apportioning doses to individuals. The habits, the sex, weight, height, activities of the emunctories, as well as the patient's previous behavior toward drugs, will assist in arriving at a conclusion. It would, obviously, be reprehensible to give a delicate woman five grains of compound elaterium powder, while it would be as short-sighted to apply one leech to deplete a navvy of six feet in stature. The environing conditions, also, must be carefully examined before a dose is selected, nor must the precise action which we expect the drug to perform be lost sight of. We have already pointed out that persons soon grow habituated to drugs, and, hence, it becomes necessary to increase the dose if

we desire to produce any appreciable effect. But many diseases seem to produce tolerance in individuals for certain drugs. It is well known what quantities of narcotics will be needed to allay the distress of cancer. The pain accompanying cancer of the uterus defies opium unless that substance be given in the most heroic doses, and even requires that these should be rapidly if not daily increased. But, on the other hand, many individuals exhibit marked susceptibility to certain drugs, so that in their case the smallest dose may act in the most baneful fashion. It becomes our duty, then, to test our patient before pushing any of the more powerful remedies.

Very many methods of computing the dose by the age of the individual have been proposed, but none quite fulfills the requirements of the case. One of the best is due to Dr. R. O. Cowling.* The rule is that the dose is represented by the quotient of the age of the patient at his next birthday divided by 24. This applies up to the age of puberty. Thus, a child of seven years would have the proportionate dose of 8 divided by 24; In infants this rule cannot be safely followed—at all events, in the case of narcotics-since, as we have shown above, they are very intolerant to this class of remedies. Indeed, so susceptible are young children to nearly all medicines that the most cautious dosing should be practiced.

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Again, the dose of medicines employed varies with the method in which they are exhibited; when we deal with modes of administration of medicines we shall have to point out that substances injected into veins act with dangerous effect, and when injected into the subcutaneous tissue the effect is far more rapid and violent than when the medicine is swallowed. These circumstances must, therefore, be borne in mind in regulating the dose.

d. The Character, Period and Form of the Disease. As pointed out above, under the heading of idiosyncrasy, every individual exhibits certain peculiarities which go some way toward modifying the disease in his particular case, and so it becomes the duty of the therapeutist not so much to treat the disease, but rather to combat it as exhibited by each individual patient. If this course be pursued, it will soon be discovered that no two cases submit themselves to quite the same routine of treatment, or evince improvement under precisely identical lines of management. In like manner, it will be found that epidemics differ very widely in their general features, and so call for diverse. treatment. In some outbreaks of typhoid fever, cerebral complications appear early; in some uncontrollable diarrhoea, while others are distinguished by the presence of confirmed constipation. And when we study the natural history of epidemics, we are struckby the fact that they individually vary in their be

* Wood's Therapeutics, p. 22.