Closely allied to the foregoing is the question of Idiosyncrasy, the constitutional peculiarity which exerts a subtle influence, scarcely understood, as potent as it is obscure. Its characteristics cannot be formulated, but must be studied with the aid of experience - an odor, a taste, a casual or fixed impression, or hereditary instinct often determining their existence and manifestation. In temperament and idiosyncrasy, indeed, the psychological rather than the physiological side of therapeutics is developed, requiring for its treatment a professional acumen not always at command.

The influence of Habit is to diminish the susceptibility of the organism to impressions which under normal conditions would be speedy and effectual. Only by gradually increasing the quantity of the dose can results be obtained which in ordinary circumstances require few exhibitions. Thus, patients accustomed to the use of alcoholic stimulants accept heroic doses of alcohol with little or no indication of the effects quickly perceptible in temperate subjects.

Bodily condition obviously affects the action of remedial agents. It is well established that in severe pain opium may be administered in quantities which in a healthy organism would produce untoward, perhaps fatal, results. The salivation occasionally caused by mercury is seldom apparent in febrile conditions. Yet in cases where sensibility is diminished great care is necessary to avoid the deleterious effects of over-stimulation or excessive dosage.

Tolerance is closely associated with habit. There may be a specific tolerance of the nature of an immunity. Thus, rabbits are known to be very resistant to belladonna, hogs to snake venom, etc. Acquired tolerance is repeatedly seen for tobacco, alcohol, and opium, and certain recent studies have attempted to show that substances related to immune bodies are elaborated by the organism, thus in part explaining the phenomena of acquired tolerance.

Respecting Sex, although it is generally admitted that females require smaller doses than males, the exceptions to the rule are so numerous as almost to vitiate the accepted theory.

The Time of Administration is closely connected with the Form of the Remedy given, as a rule remedies being withheld immediately before and after meals. The practice, however, is subject to modifications, certain drugs acting best on an empty stomach, and others, such as local irritants, being more safely diffused when the stomach is full, in which case by mingling with the food they are not brought into irritating contact with the intestinal mucous membranes.

With regard to Intervals between Doses it may be said, in brief, that they are to be determined by the special features of the case, the character and potency of the drug, and the degree of tolerance and assimilation evidenced by the patient. Every remedial agent, under normal conditions, produces a specific and definite action, the system by absorption and elimination limiting the period of its efficacy in cases of prolonged treatment, so that the drug is evidently to be renewed in order to secure perfect results. Failure to continue treatment has frequently proved disastrous, even fatal, to the patient, and it should be borne in mind that, in the absence of contraindications or untoward effects, a primary object of dosage is to create and maintain an impression upon the morbid system.

Repeated dosage with tardy elimination may lead to cumulative action. Thus, while dose for dose ethyl alcohol is more toxic than methyl alcohol, repeated doses of methyl alcohol are more highly poisonous, from slow elimination, than doses of ethyl alcohol. The chronic poisoning by the heavy metals, arsenic, mercury, or lead, is an illustration of a type of cumulative action. The iodides and bromides show similar phenomena. Digitalis is a classical example.

Other considerations - by some therapeutists held to be of minor, by others of paramount, importance - affect the vital question of dosage. The emotions, for example, play an interesting part in the toleration or rejection of remedial agents. Strangely enough, too, the imaginative faculty is often a cause of idiosyncrasy, numerous instances being adduced by reputable authorities wherein either positive or fancied ills were affected through the agency of spurious remedies - bread-pills, deceptive concoctions, and the like - the ethical aspect of therapeutics being here left to the conscience of the physician.

Pathological states are important modifiers of drug action. Thus, in chronic nephritis drugs which do not modify the kidney epithelium are used. Effort is made to obviate such activities. In high temperature the many synthetic antipyretics act very rapidly while having very little effect in health. In the case of parasitic diseases such as trypanosomiasis or malaria, the action of trypan-red or of quinine is naturally and entirely a different action than when given to a healthy person. In certain intestinal diseases associated with acid diarrhea, and with diminished alkalinity of the intestinal canal, the use of synthetic remedies which are only broken down into their constituent parts by alkalis is obviously useless.