Incompatibility may be Chemical, Pharmaceutical or Therapeutical, according as the incompatible combination results in chemical decomposition, physical disassociation, or antagonistic physiological action. The first kind may be intentional, for the purpose of obtaining a new substance as the result of the chemical action;—for example, the prescribing Calomel or Corrosive Sublimate with Limewater, to produce respectively the black and yellow Oxides of Mercury.
The Dangers of Incompatibility may in a great measure be avoided by the use of the utmost simplicity in prescribing. The subject can only be glanced at within these pages, but the following simple rules may help the burdened memory of the student and the practitioner.
Never use more than one remedy at a time, if one will serve the purpose.
Never use Strong Mineral Acids with other agents, unless you know exactly what reaction will ensue. They decompose salts of the weaker acids, and form ethers when combined with alcohol. Never combine free acids with hydrates or carbonates.
Select the simplest solvent, diluent or excipient you know of, remembering that the solvent power of alcohol and of water for their respective substances decreases in proportion to the quantity of the other added.
Generally do not combine two or more soluble salts; for such salts in solution, when brought together, usually exchange their radicles, thereby forming an insoluble compound.
- The following more or less insoluble salts will be formed whenever the materials of which they are composed are brought together in solutions; the Hydrates, Carbonates, Phosphates, Borates, Arsenates and Tannates of most earthy and heavy metals and alkaloids, and the metallic Sulphides; the Sulphates of Calcium, of Lead, and the subsalts of Mercury; the Chlorides, Iodides, and Bromides of Bismuth, Silver, Lead, and Mercury; the Iodides of Quinine, Morphine and most alkaloids.
Never order a drug in combination with any of its Tests or Antidotes.
Never prescribe a Glucoside (as Santonin, Colocynthin, etc.), in combination with free acids or with a substance containing Emulsin, as these agents will decompose it.
Aconite should be ordered in water alone, Corrosive Mercuric Chloride by itself in water or in simple syrup. The latter drug is incompatible with almost everything, even the Compound Syrup of Sarsaparilla being said to decompose it.
Potassium Iodide decomposes most of the metallic salts, and is one of the drugs which are best administered alone.
Resinous Tinctures or Fluid Extracts, (e. g., Tinct. Cannabis Indicae) when combined with aqueous solutions, should always have Acacia or some other emulsifying agent added, to prevent the separation of the resin, which otherwise will be deposited on the sides of the bottle or will float on top of the mixture.
Silver Nitrate and the Acetate and Sub-acetate of Lead, though incompatible with almost everything, may be combined with Opium, the latter forming with Opium a compound, which, though insoluble, is therapeutically active as an astringent and anodyne lotion. Silver Nitrate with Creosote forms an explosive compound.
Tannic and Gallic Acids, and substances containing them (as the Astringent Bitters), precipitate albumen, alkaloids and most soluble metallic salts. They may be prescribed with the proto-salts of Iron, but not with its per-salts. Calumba is the best vegetable tonic to use with Iron salts, as it contains neither tannic nor gallic acid. Tannic Acid precipitates gelatin.
Iodine and the soluble Iodides are incompatible with the alkaloids and substances containing them, also with most metallic salts.
Alkalies neutralize free acids, and precipitate the alkaloids and the soluble non-alkaline metallic salts. Oxides of the Alkalies decompose salts of the metals proper, and salts of the alkaloids, precipitating their bases; but the base may be soluble in an excess of the alkali.
- Poisonous Compounds may be formed by the admixture of several substances in solution, such as—
- Potassium Iodide or the Syrup of the Iodide of Iron,—with Potassium Chlorate.
- Potassium Cyanide or Dilute Hydrocyanic Acid,—with Calomel, Bismuth salts, metallic hydrates, carbonates, subnitrates or subchlorides, forming poisonous cyanides.
Explosive Compounds result from mixing powerful oxidizing agents with others which are readily oxidizable. The chief members of these two classes are as follows—
|Oxidizers.||Oxidizable or Combustible.|
|Nitric Acid. Chromic Acid.||Glycerin, Sugar, Alcohols.|
|Free Hydrochloric Acid.||Oils and Ethers.|
|Nitro-hydrochloric Acid.||Sulphur and Sulphides.|
|Potassium Chlorate.||Dry Organic Substances.|
Table of Precipitant Solutions.
The following table shows the most important instances of solutions which mutually precipitate each other, the letter P meaning "forms a precipitate with"—
|Carbonic Acid and Carbonates,||P||P||P||P||P||P|
|Sulphuric Acid and Sulphonates,||P||P||P|
|Phosphoric Acid and Phosphates,||P||P||P||P||P||P|
|Boric Acid and Borates,||P||P||P||P|
|Hydrochloric Acid and Chlorides,||P||P|
|Hydrobromic Acid and Bromides,||P||P|
|Hydriotic Acid and Iodides,||P||P||P|
Pharmaceutical Incompatibility differs from chemical incompatibility in the absence of chemical action, and is generally produced by adding one substance to another which, through differences in solubility, causes a precipitation of solid matter or a separation of part of the liquid. The constituents separated may be active and hence important, or inert and therefore unimportant. Instances of this are—the addition of an acid to a Quinine and Liquorice mixture, resulting in precipitation of the Glycyrrhizin (relied on to cover the taste of the Quinine) by the acid;—or the use of Quinine, Tincture of Ferric Chloride and Liquorice together;—or the prescribing of solutions of Chloral and Potassium Bromide with an alcoholic preparation, the Chloral separating to the top as an alcoholate, and therefore dangerously in excess for the first few doses.
When a fluid extract is diluted with a liquid differing in composition from those used in the fluid extracts, the gum, albumen, resin, and mucilage are often separated. In such a case as Fluid Extract of Cannabis Indica, the active resin would be thrown out of solution, and floating on top might cause serious symptoms; but in many other instances the precipitate would be inert and filtration would be in order. Water is the solvent for albuminous, gelatinous, gummy, and saccharine bodies and for a large number of inorganic salts; while Alcohol is the solvent for volatile oils and resins, gum-resins, resinoids, balsams, and all drugs containing these as their active principles. The solvent power of either Alcohol or Water for their particular substances decreases in proportion to the amount of the other added.
- Instances of Pharmaceutical Incompatibility.
- Resinous Tinctures or Fluid Extracts with Aqueous solutions.
- Tincture of Guaiac with Spirit of Nitric Ether.
- Compound Infusion of Gentian with Infusion of Wild Cherry.
- Compound Infusion of Cinchona with Compound Infusion of Gentian.
- Essential Oils with Aqueous liquids in quantities exceeding 1 drop to ℥j.
- Fixed oils and Copaiba with Aqueous liquids (except excipients).
- Tinctures made with Alcohol with those made with Diluted Alcohol.
- Alcoholic Tinctures and Fluid Extracts with Aqueous preparations.
- Spirit of Nitrous Ether with strong Mucilages.
- Infusions generally with Metallic salts.
Therapeutical Incompatibility arises when two agents are administered together which oppose each other in their action on the human system,—as for instance Belladonna in any form with Physostigma. But in many cases physiological antagonists are designedly prescribed together, one as a guard against the action of the other, as in the hypodermic administration of Morphine guarded by Atropine. The antagonists to each of the active medicinal agents may be found in the preceding pages under their various titles.
A Compend of Materia Medica, Therapeutics, and Prescription Writing, 1902, by Sam'l O. L. Potter, M.D., M.R.C.P.L.