Many of the drugs and preparations of the materia medica may be and are given alone, but many others only in combination. There are a few which are never or almost never given in combination with other drugs, but the majority of drugs and their preparations are at times given in combinations, which are often very complex. The selection of drugs and preparations to be used in combination with each other requires a great deal of care to avoid unwished for changes being brought about by thier admixture. Two drugs are said to be "incompatible," when on being brought into intimate contact with each other unwished for changes either physical or chemical are brought about or when their pharmacological actions would so interfere with each other as to be detrimental. It is by no means an infrequent occurrence for a physician to prescribe together two medicines which have almost opposite pharmacological actions but he does so in such proportions that the action of the one serves but to correct some undesired action of the other.

Incompatibility dependent upon the differing pharmacological actions of the drugs administered together is known as Therapeutical or better Pharmacological Incompatibility. An extreme example would be the administration of atropine and pilocarpine together.

Incompatibility dependent upon chemical and physical changes can only occur when the drugs are brought into intimate physical contact either by trituration in a mortar (the cases in which incompatibility is apt to make be made manifest in this way will be found mentioned in paragraphs IVd. and V.) or by solution. The incompatibility due to chemical changes occuring between preparations dispensed together is known as Chemical Incompatibility. The changes may be of several types and may be classified as follows: -

I. Resulting in chemical change without any visible change.

(a) The neutralization of acids by bases. *

(b) The breaking up of glucosides by acids (sugar is set free and the glu-coside loses in activity).

(c) The action of acids on the activity of pancreatic ferments and of alkali on gastric ferments.

2. Resulting in precipitation of newly formed chemical substances due to the interaction of two other chemical substances in solution.

* Important cases are printed in italics.

(a) Salts of the alkaline earths are precipitated by alkali hydroxides and carbonates, phosphates, borates, oxalates (the corresponding insoluble salts of the alkaline earths being formed). The free acids which would form corresponding salts are also incompatible.

(b) Salts of the metals in solution are incompatible with hydrates, carbonates, phosphates, oxalates and the corresponding acids; in many cases with proteins, tannins, acacia and often alkaloids and phenozone. Silver, mercurous, lead, and bismuth salts also with bromides and iodides: the same metals and calcium, barium and strontium, with sulphates and sulphuric acid.

(c) Hydrates or carbonates of the alkalies, sodium, potassium, and ammonia with salts of metals and alkaline earths, and with alkaloids and some glucosides.

(d) Alkaloids form insoluble salts with other organic acids than acetic and citric; the free alkaloid being very much less soluble than the salts is precipitated by alkali hydrates and carbonates and by borax. Ammonium carbonate and the bicarbonates do not so readily cause precipitation. Iodides, bromides, salicylates, benzoates, usually cause a precipitate tannic acid, and iodine in a solution of mercuric iodide; precipitation may be prevented in many of these cases by from 15-50% of alcohol. About 15% suffices to prevent that by bicarbonates and carbonates. Alkaloides may give a precipitate with many metallic salts especially those of mercury.

(e) Proteins are precipitated by alkaloids, many metal salts, tannin and alcohol.

3. Resulting in a change of colour owing to the formation of some soluble but undesired body owing to the interaction of two other substances in solution.

(a) Giving an objectional appearance tannic and gallic acids and iron preparations, ammonia and carbolic acid; gallic acid and thymol. Ferric chloride with salicylates, carbolic acid, creasote, guaiacol, salol, acetanilid, phenazone, phenacetin, oils of wintergreen, cloves, pimenta, and thyme, podophyllin, aloin, gamboge, asafetida, storax, myrrh, balsam of Peru, balsam of Tolu, morphine and apomorphine.

(b) The change in colour is the indication of a chemical change objectionable from the pharmacological side also. Salicylates, phenozone, acetanilid, with the free nitrous acid in Spirits of Nitrous Ether (isonitroso-compounds are formed).

4. Resulting in the chemical splitting of one of the bodies and the formation of an undesired body.

(a) Resulting in the freeing of a volatile body, which may in part or entirely, dependent upon the amount formed, remain in solution. Hydrochloric acid with nitric acid (nitrous oxides freed); strong acids with alcohol (ethers); acids and carbonates; acids and sulphides; mineral acids with iodides, bromides, and chlorates; ammonium salts and hydrates and carbonates of the alkalies.

(b) Resulting in the freeing of a liquid body, chloral and butylchloral with alkalies (chloroform freed).

(c) Resulting in the freeing of dextrose or other sugar, glucosides with acids and alkalies.

(d) Resulting in liberation of so much gas suddenly as to cause an explosion. Chromic acid, concentrated nitric acid, nitrates, permanganates, chlorates, with such substances as sulphur and sulphides, sulphites, iodides, phosphorus, hypophosphites, reduced iron, and many organic bodies, sugar, tannin, etc. These reactions only occur when the dry substances are triturated together or in some cases when mixed in very concentrated solutions.

5. In some cases when two solids are triturated together a soft sticky or a damp mass, or a liquid is formed: the reaction is probably always to a certain extent chemical. Such substances are camphor, carbolic acid, thymol, phenozone, phenacetin, chloral, sodium phosphate, lead acetate. Details will be found under the various drugs.