quently, in all such conditions a drug whose action is immediately desired must be given by some other avenue than the stomach.

Most drugs are satisfactorily given after meals, unless they are known to seriously delay digestion, and many drugs retard digestion more or less. A drug known to greatly delay digestion should be given two hours after meals,or long before a meal. An irritant drug or preparation should ordinarily not be given on an empty stomach, unless the drug is well diluted. A drug that irritates the stomach may cause pain and vomiting, or may cause inflammation and even ulceration. Some drugs may irritate, and at the same time not cause recognizable pain. This is true of some tablets, such as bromides, chloral, potassium chlorate, etc. Hence only tablets known to be absolutely non-irritant should be swallowed whole.

Some drugs are destroyed in the stomach, or are at least changed so that their activities are impaired, or they may cause nausea. Such drugs may be given in pills coated with some protective covering that is not acted upon by the gastric juice. The hydrochloric acid of the stomach may chemically change many drugs and preparations, but generally not to their impairment, and such changes often hasten absorption. It is obvious, if the mucous membrane of the stomach is to be treated, that medicaments must be given on an empty stomach. It is also obvious that a bitter tonic, or a gastric stimulant or appetizer should just precede the meal. The more soluble the drug is in acid media and the better the solution of the drug, the quicker it must be absorbed. However, speed of absorption is not always a necessary requirement, hence very many drugs are given in less soluble, but more pleasant, forms than solutions.

2. Intolerance.-Many conditions may cause an intolerance to a drug. In other words, an average dose of a drug may cause unexpected, unpleasant, or severe symptoms. Certain diseases, especially of the central nervous system, of the liver, of the kidneys, and some diseases of the endocrine glands may cause an intolerance to certain drugs. On the other hand, some individuals who are well are intolerant to certain drugs and remain so all their lives. This is termed an "idiosyncrasy" against such drugs. The drugs against which there is most frequently

an idiosyncrasy, or intolerance, are belladonna and iodides. Drugs against which there is less frequently intolerance, but common enough to be noted, are opium and its alkaloids; mercury, especially calomel; bromides (even a single dose often causing an eruption); quinine; and salicylates. An individual who cannot take morphine or any other narcotic for severe pain is very unfortunate, but such a patient is occasionally found. Some patients cannot take quinine without being severely poisoned. Others, after the first poisoning symptoms from quinine or some other drug, become more or less tolerant and can take ordinary doses of it for that particular period, to be again poisoned at some other time. Some of these excessive reactions from drugs are anaphylactic in character, being accompanied by fever and other symptoms of anaphylaxis. An individual found to have an idiosyncrasy against any particular drug should be informed of the fact, that he may warn his future physicians and not be again unnecessarily poisoned.

3. Tolerance.-Certain diseases cause a tolerance for certain drugs, such as most patients with malarial fever will tolerate large doses of quinine; those with syphilis, large doses of mercury and iodides; those with epilepsy large doses of bromides. Also, certain diseases of the endocrine glands cause a tolerance to drugs. A tolerance to a drug is acquired by long taking of that drug, and such tolerance is found in drug addicts, those who use morphine or cocaine, in excessive users of tobacco, and even in those who constantly use cathartics. Such individuals become tolerant to the class of drugs to which they are accustomed, and may be intolerant to other drugs.

CUMULATIVE EFFECTS OF DRUGS

The cumulative action of a drug is evidenced by sudden unexpected mild symptoms of poisoning. This occurs when certain drugs are given in too rapidly repeated doses, so that excretion of one dose cannot occur before the next one or more doses are taken. The result is an accumulation of the drug in the system until there is developed a sudden intolerance, and more or less severe poisoning occurs. At other times, owing to

some sudden disturbance of the organs of excretion a drug ordinarily well excreted is retained, and poisoning occurs.

Another form of cumulative action takes place when certain drugs have been long taken and symptoms of chronic poisoning occur. At times certain drugs are pushed to the degree of primary poisoning, or until full physiologic limit is reached, to obtain desired therapeutic results. This is done deliberately, and the first symptoms of poisoning are watched for and quickly noted, and the administration of the drug is stopped.

The recognition of the over-action of a drug, the recognition of chronic drug poisoning, perhaps not even suspected, and the treatment of these conditions can be acquired only by book and laboratory study of the pharmacology of drugs.

It should be borne in mind when giving drugs to nursing mothers that many drugs are excreted in the milk, and may affect the child. These drugs are opium and its alkaloids, most hypnotics, bromides, arsenic, mercury, iodides, quinine, thyroid extract and probably other organ extracts, and most cathartics. At times, however, it is desirable to treat a babe through its mother's milk.

Many drugs cause eruptions on the skin, most frequently an urticaria or an efflorescence, similar to the scarlet fever rash. Part of this action is due to duodenal irritation quite similar to a food poisoning, as from fish or strawberries, which foods so frequently cause eruptions in some individuals. The drugs most likely to cause eruptions are arsenic, atropine, chloral, coal-tar drugs as antipyrine and phenols, copaiba, opium, quinine, mercury, salicylic acid and some salicylates, santal oil, synthetic hypnotics as sulphonal, thyroid, and volatile oils. At times these drugs, in a few individuals, may cause real anaphylactic conditions, with serious eruption and swelling of the skin, or a dermatitis, giant urticaria, or angioneurotic edema. Antitoxins and serums may cause such symptoms, and may even cause death from protein poisoning.

Some drugs cause irritation of the skin during their excretion through the glands of the skin. Bromides, especially if long taken, often cause pustular acne, and at times more serious skin eruptions. Iodides cause non-pustular acne.

DRUGS WHICH MAY CHANGE THE COLOR OF THE URINE

Drugs that increase the amount of urine cause it to be lighter, while drugs that irritate the kidneys cause the urine to be darker. Methylene blue causes the urine to be green, if it is acid. Phenol, or any phenol containing drug, may cause the urine to be dark brown. Santonin causes it to be yellow, if acid; purple, if alkaline. Senna may cause it to be red, if

alkaline; yellow, if acid. Sulphonal and other synthetic drugs may cause the urine to be dark.

DRUGS WHICH COLOR THE FECES

Bismuth salts color the feces black or dark gray; iron colors them black; colchicum and mercury in sufficient doses to cause purging color them green; and vegetable purgatives cause them to be darker than normal.

ADMINISTRATION OF DRUGS

Some drugs act locally only, when applied to the skin and mucous membranes, or to the gastrointestinal canal. Even many cathartics act as such on account of the irritation of the intestinal walls that they cause. Drugs that act on some part of the general system must first be absorbed into the blood, and they reach the blood: (1) by absorption from the stomach and intestines after their administration by the mouth in capsules, pills, tablets, liquids, or powders; (2) by absorption from the rectum after their administration as suppositories or enemata; (3) by absorption from any other mucous membrane with which they are in contact; (4) by absorption after their inhalation; (5) by absorption from the skin after their inunction or after their prolonged contact with the skin; (6) by absorption from the subcutaneous tissues after their hypodermic injection; (7) by absorption from muscular tissue after their deep injection (8) by their direct introduction into the blood stream by intravenous injection.

RAPIDITY OF ABSORPTION

This occurs in the following order, the most rapid route heading the list:

1. When the drug is given intravenously.

2. When the drug is given hypodermatically.

3. When the drug is brought into contact with mucous membranes, especially the nose.

4. When the drug is given by the stomach. 5. When the drug is given by the rectum. 6. When the drug is rubbed into the skin.

The size of the dose depends on the rapidity of the absorption; in other words, the dose should be the smallest when it is given intravenously, and the largest when it is rubbed into the skin. The length of time before a given dose will be excreted is in the inverse order of the above list.

For certain diseases and conditions drugs and serums are administered intraspinally.