Example of Tannic Acid and Morphine Incompatibility

see a good example of true 15 16 PRESCRIPTION INCOMPATIBILITIES incompatibility. The physician apparently prescribed the tannie acid as an astringent to stop a discharge in the ear; the canal of the ear being painful, he also prescribed mor- phine sulphate with the intention of diminishing the pain, but this latter object is completely defeated, because the morphine sulphate is converted into the insoluble morphine tannate, which being insoluble cannot be absorbed and can- not act. Even the astringent action of the tannic acid is diminished, because a part of the latter is precipitated and is in combination with the morphine. 2. Morphinae Sulphatis . . gr. iv Ammonii Carbonatis .. 5 jss Syr. Senegae “we 5 Aquae qs.ad 3 iij S. Teaspoonful 4 times a day, as directed. A very common prescription, but incompatible neyerthe- less. The morphine is precipitated in the alkaloidal form by the ammonium carbonate which is a strong alkali. Of course putting a shake label on the bottle diminishes the danger to a’ great extent, but it does not entirely eliminate it. As a general rule mixtures with poisonous precipitates or sediments should not be dispensed. In the above prescription, the syrup of senega alone would have a tendency to precipitate the morphine because it con- tains some water of ammonia. ALKALOIDS ARE PRECIPITATED BY, AND THEREFORE INCOMPAT- IBLE WITH, ALKALINE Hyproxipes, THEIR CARBONATES AND BI- CARBONATES AND WITH SALTS HAVING AN ALKALINE REACTION. Such are: potassium hydroxide, carbonate and bicarbonate; sodium hydroxide, carbonate and bicarbonate; ammonium hydroxide (=ammonia water) and carbonate; calcium hydroxide (= lime water) ; sodium borate and sodium phos- phate, the latter salts having an alkaline reaction. Magnesium hydroxide, Mg(OH),, has the same tendency, but its solu- bility is very slight and it is seldom prescribed in combina- tion with alkaloids. PRESCRIPTION INCOMPATIBILITIES Ww 3, Morphinae Sulphatis gr. ij Antimon, et Potass. Tartrati: gr. ij Ammon. Chlori 3j Syr. Pruni Virgin. ........ 5 ij Tannie acid is an excellent precipitant of tartar emetic (the precipitate formed is antimony tannate), and wild cherry contains a large amount of tannic acid. The morphine will also be precipitated, as morphine tannate. It is true that “no reports of bad results have ever reached me—probably because the precipitates are so well suspended in the thick syrup. Nevertheless, the combination is not a good one. If it is dispensed, a ‘‘shake’’ label should invariably accom- pany it. Tannic Acip Precrprrates AND Is THEREFORE INcoMPATI- BLE witH Tartar Emetic (AnTIMoNY AND Porasstum Tar- TRATE). 4, Fluidextr. Cannabis Indie. Kali Bromati . Aquae Menthae Pip. . 3 ij el att} The resins contained in the cannabis indica precipitate when added to water. The finely divided precipitate grad- ually collects in little lumps. A nice homogeneous mixture can be made by rubbing the fluidextract with one or two drams of acacia, and then gradually adding some water so as to form an emulsion. The mixture will also have a much less disagreeable taste; so that both from a pharmaceutical and a gustatory point of view the employment of acacia is not only justifiable, but clearly indicated. This is a typical example of pharmaceutical incompatibility. Restnous FLumexTRacts AND ‘TINCTURES PRECIPITATE Wuen Mixep wir Water. idi 5, Hydrogenii Per Aquae Calcis . S. Use for throat in atomizer. On mixing the two solutions a whitish precipitate is n0- +++ .8a 60.0 18 PRESCRIPTION INCOMPATIBILITIES ticed. This precipitate is generally considered to consist of calcium sulphate or calcium phosphate, the formation of those precipitates being due to the sulphuric or phosphorie acid contained, in small amounts, in the peroxide of hydrogen. This explanation is true as far as it goes, but it does not go far enough. The precipitate also occurs in varieties of peroxide of hydrogen which contain no sulphuric or phos- phorie acid, but only hydrochloric acid. It certainly cannot be due to the latter, because calcium chloride is a very solu- ble salt. No, the chief precipitate is due to the formation of calcium peroxide, which is a white crystalline compound. The equation is a simple one: Ca(OH).+ H:0:= CaO: + 21.0. The question under discussion is not one of theoretical interest only; it is of great practical importance. If the pre- cipitation were due to the formation of calcium sulphate or phosphate only, no objections could be raised to the preserip- tion. In fact, except for the precipitate clogging the holes in the atomizer, the addition of lime water to peroxide of hydrogen might be considered an advantage, because the acid- ity of the latter becomes neutralized and the sharp burning taste is lost. But having learned that the peroxide becomes decomposed, we see that the combination is an inadmissible one. Ir Is Best Nor to Prescrise Limz WATER AND PEROXIDE or Hyprogen IN THE SAME Mrxrure. I might add that calcium peroxide is a commercial prod- uct, being sold under various names as a gastrointestinal anti- septic. gr. ij gr. iij 3 iv 6. Protargol ..... Zinei Sulphatis . Aquae Destillatae ..... M4. Collyrium. This prescription is absolutely incompatible. On adding the zine sulphate to the protargol solution the latter becomes PRESCRIPTION INCOMPATIBILITIES 19 completely decolorized, while at the same time a rather abun- dant precipitate takes place. (The precipitate is soluble in ammonia water.) To dispense it with the precipitate is of course inadmissible, the prescription being intended for an eye wash, or eye drops. The druggist who received this pre- scription, dispensed it after filtering out the precipitate. A very poor way. It is much better to leave out the sulphate of zine and notify the physician. Protarcou Is AssoLuTeLy INcomMPATIBLE wiTH Zinc SuL- PHATE. Gm ae err CDIOTIAL o)ccisy sense cc scniieeeiein cee es 5 ss Syr. Simplicis ... _ we 5d Aquae Cinnamomi ........0.6.05 ad 3 iv It does not seem as if anything could be the matter with this innocent prescription, but there is. The cinnamie alde- hyde present in the oil of cinnamon (from which the water is prepared) reacts with the ferric chloride; the solution, at first clear, becomes after a short time turbid and dirty-looking, and a slight deposit forms. It is best to substitute another water for the cinnamon water, with the physician’s knowl- edge, of course, but if the prescription must be dispensed as written, the patient should invariably be informed of the change in the appearance which the medicine will undergo in a few hours. Otherwise he will be almost sure to bring it back the next day, with the question if a mistake had not been made, or if the medicine did not get spoiled. If the patient is prepared for such a thing he will never make any fuss about it; on the contrary, his respect for the druggist’s knowledge and predicting powers will be greatly increased. 8. Tr, Ferri Chloridi ....... Spir. Pimentae Syrupi Sacchari . Aquae ........ The Eugenol present in the oil of pimenta reacts with the ferric chloride, producing a turbidity in the mixture, with the 20 PRESCRIPTION INCOMPATIBILITIES final deposition of a dark-brown precipitate... The same reac- tion takes place if Aqua Pimentae is used instead of the: spirit. The remarks concerning the preceding prescription apply also to this one. 9. Acidi Tannici . Aquae Caleis . S. Use as a gargle. Tannie acid is incompatible with lime water. When the two are mixed, a bulky, bluish-white precipitate results. The precipitate is a tannate of calcium, though its composition is somewhat variable. The prescription should hardly be dispensed, Lime Water anp Oruer Souusie Caucrum Saurs Arg In- COMPATIBLE witH TANNiIc AcID. 10. Glyceriti Ac. Tannici - Aquae Caleis S. Use as a gargle. The same reaction takes place here, only the precipitate is of a whitish color and is, on account of the glycerin, more evenly distributed. This prescription may be dispensed, but it is best, perhaps, to call the physician’s attention to the incompatibility. 3 ij “Syd 11. Atrop. Sulphatis gr.v Ext. Colehici Sem. Fl. . 53 Potassii Iodidi .enx Sodii Salicyl . . gr. xx ‘Tr. Guaiaci . 58s Aquae Foeniculi . ad 3 ij S. 3 i every four hours. I present this prescription not so much for its incompatible points as for its peculiar dosage. When the doctor was told that the dose of atropine—l4 of a grain—was a lethal one, he answered irascibly that he did not wish to be bothered in the future; that we knew he was not well up in doses, and that therefore we could fix the doses to suit ourselves! He PRESCRIPTION INCOMPATIBILITIES 21 afterwards gave us carte blanche so far as his prescriptions were concerned ; we could change the dosage, leave out ingre- dients (incompatible ones), ete. Very often he only wrote the ingredients, leaving it to us to fix the quantities. He has a very large practice, nevertheless! The incompatibilities are: the KI with the atropine (and perhaps with the colchicine), and the tincture of guaiae with the water (the resin precipitates at once). The tincture sometimes strikes a blue color with acacia, but the latter may be used to make an emulsion, in spite of this. 12. Argenti Nitrici Aquae Destillat . Detur in vitro nigro et sign + gr. xv Sor Pro usu externo. This is a perfectly innocent and compatible prescription, but the making up of it afforded a good deal of amusement ; the senior, the junior, and even the boy joined in the result- ing merriment. The incident related here took place in the old land-mark pharmacy, at the corner of Houston and Clin- ton streets, this city, H. L. Metz and then Nicholas Tauszig, proprietors. It was on a Sunday, the boss was out, and busi- ness was exceedingly rushing. One hundred and fifty to two hundred prescriptions a day was the general average, but that day the number was much greater. There were besides quite a few “‘hard”’ prescriptions, such as 500 silver-coated creo- sote pills, 120 suppositories, 500 cachets, ete. A sign was therefore put out: ‘‘Relief clerk wanted.’’ Soon a young man presented himself, who said he had worked in a drug- store on the other side, but could find no position here and would be glad to relieve for $2.00 an afternoon. The first two prescriptions he made up all right. The third préscrip- tion was the above. He went to the poison closet, where we used to keep all’ potent drugs, found the bottle with the label Argentum nitricum, weighed out the alleged silver ni- trate, put it in a bottle, added the water, and started shaking it; after shaking violently for two or three minutes, finding 22 PRESCRIPTION INCOMPATIBILITIES that the ‘‘silver nitrate’’ would not dissolve, he emptied the contents into a mortar, and started to pound the ‘‘silver nitrate.’’? This, of course, caused surprise to his fellow-pre- scriptionists, and on looking into the mortar it was found that the alleged silver nitrate was—flaxseed! As you perhaps know, fused silver nitrate formerly used to come in bottles filled with flaxseed. This was done to prevent the sticks from breaking. He was unfamiliar with the fact and thought, so he said, that the flaxseed was a special form in which silver nitrate came in this country. But we suspected that he had never handled silver nitrate before. 18. Magnes, Calein, ......-seeeseneeees oe 3 ij Puly. Rhei i ee Puly. Zingiberis 3j Sodii Bicarbon. . . nl Olei Menthae Pip. . gt v Aquae .....+04 ad 3 iv After standing for a while this mixture thickens and solidi- fies to such an extent that it is impossible to either shake it or pour it from the bottle. The cause of it is to be found exclusively in the tendency of magnesium oxide to combine with water, forming a gelatinous hydrate: MgO + H,O= Mg(OH),. If the heavy calcined magnesia—magnesii oxidum ponderosum—be used instead of the light magnesia, the ten- dency to gelatinization will be greatly obviated. Sometimes even when the light magnesia is used, no gelatinization takes place. This is due to the sad fact that in some drug-stores magnesia is handled so carelessly (left in open vessels, in a moist atmosphere, ete.), that in a short time the magnesia is no longer magnesia, but magnesium carbonate (that is, hydro- carbonate), and this latter does not gelatinize with water. I have seen many such samples of ‘‘magnesia.’’ 14, Spir. Ammon, Armat. . Spir. Menth. Piper. . Aquae Calcis S.: 3 ss after meals, PRESCRIPTION INCOMPATIBILITIES 23 A slight precipitate of calcium carbonate will be formed, due to the ammonium carbonate in the aromatic spirit. The oils of both spirits will be precipitated by the lime water, making a milky mixture; an inelegant combination but one that may be dispensed with a ‘‘shake’’ label. 15. Acidi Carbol. ......e0eceeeeeeeeeeeeeeeees ett. x Natrii Bibor. | 3a Natrii Bicarb. 3 ij Glycerini 3j Aquae 5 viij S.: Use with nasal douche. This is practically the well-known Dobell’s solution, only modified in the proportions of the ingredients. An efferves- cence takes place, due to the evolution of carbon dioxide. What is this evolution due to? “To the action of the car- bolic acid on the sodium bicarbonate,’’ many would answer. No; it is caused by the action of the boric acid on the sodium bicarbonate ; the boric acid being formed by the action of the glycerin on the borax. A full discussion of this subject will be found in another prescription. 16. Potassii Iodidi Tr. Ferri Chloridi . Aquae . S.: 5j tid. p It is not advisable to dispense this prescription, as a con- siderable amount of iodine is liberated; not only by the free hydrochloric acid present in the tincture, but by the ferric chloride itself, thus: 2QKI + Fe:Cle=2F eC. + 2KCl + Is Ir Is Best Nor ro Prescrise TINCTURE or Ferric CHLORIDE witH Porasstum IoprpE. 17. Potass. Brom. Sodii Brom, ...... Aquae Camphorae . 24 PRESCRIPTION INCOMPATIBILITIES While camphor is soluble to a very slight extent in water, it is almost absolutely insoluble in solutions of salts. In this prescription it is therefore precipitated out, floating on the top of the liquid or adhering to the bottle as a fine seum. Satrs SHoutp Nor Be Prescrisep to Be DissoLvep IN Campnor Water, ParticuLARLY In CONCENTRATED SoLuTIONS. 18. Quinin. Bisulph . on Amm. Carbon. ... ook Syr. Simpl. .. Beil Aquae Cinnam 34 8.: 5 i doses. Attention has been called to this incompatible prescription times without number, nevertheless it seems to be a favorite with many physicians. Why physicians will preseribe the most soluble quinine salt and then precipitate it is beyond comprehension. ‘There is only one explanation for it: the physician is not aware that a precipitation takes place. The quinine bisulphate, being seventy times more soluble than the sulphate, dissolves easily in the prescribed quantity of water; but the ammonium carbonate (like all alkaline car- bonates) causes a precipitate of alkaloidal quinine. ALKALomAL Sats Are Turown Our or Souurion By AL- KALINE Hyproxipes AND CARBONATES. 19. Hydrarg. Bieblor. .. . gr. Vj Syrup Hypophosphit. 5ij Syr. Sarsap. Co. al Aquae Menthae Pip. 53 S.: 554 times a day. This prescription is absolutely incompatible. The hypo phosphites are strong reducing agents, and the corrosive sub- limate is entirely reduced: first to calomel and then to metal- lic mercury. Hither the corrosive sublimate or the hypophos- phites must be omitted. Corrosive Susumate aAnp HypopHospHires ARE Asso- LUTELY INCOMPATIBLE, PRESCRIPTION INCOMPATIBILITIES 25 20. Argenti Nitratis ... +. gr. iv Syr. Hypophosphit . a 8) Aquae Dest. -qs.ad 3 iv S.: 3 j after meals. This prescription, too, is absolutely incompatible. The hypophosphites reduce the silver nitrate to black metallic silver. The organic constituents of the syrup also help along the decomposition. There is no way of dispensing the above, except by leaving out either the first or second ingredient. The method of administering silver nitrate in solution is irra- tional. On coming in contact with the saliva and the secre- tion from the esophagus, the nitrate becomes almost entirely decomposed. If an effect on the bowels or a systemic effect is desired, the best method is to administer the remedy in the form of enteric pills; i. e., pills coated with salol or keratin. 21. Cocain. Hydrochlor. .......0+-.0+ een.. gr. xx Atropin. Sulph. .. gr. ijss Aconitin. gr. j Collodion . 4 % . ay S.: Paint over painful spots when pain is acute. As cocaine hydrochloride is practically insoluble in ether, and as collodion consists of gun-cotton dissolved in a mixture of 3 volumes of ether and 1 of alcohol, the alkaloidal salt will not dissolve. One of two things may be done: Hither dissolve the cocaine and other alkaloidal salts in a little aleo- hol (it would require about 114 dr.), and mix the solution with the collodion; or employ alkaloidal cocaine, which is very soluble in ether. The latter course is preferable. The two last alkaloidal preparations need not be changed, as they are in such small quantity that the alcohol present in the collodion will dissolve them without much difficulty. 22. Sol. Magendie Ol WOWIEKL crises sesenssvaseereesccessece. 08 0,0 S.: Gtt. viii tid. p. e. Well do I remember this prescription, as it was the first incompatible one I ever saw. It was almost at the very com- 26 PRESCRIPTION INCOMPATIBILITIES mencement of my pharmaceutical career. The proprietor mixed the two solutions, affixed the label, but, on delivering it, noticed a precipitate throughout the entire bottle. He seemed to be surprised, and went again behind the counter, mixed the solutions in different order, but with the same re- sult. After two or three more unsuccessful attempts, I was sent to the doctor. ‘‘Oh, well, if they don’t go well together, leave out the morphine,’’ said the doctor. Thus, ignorance deprived the patient of the ingredient which he was prob- ably in need of. Alkaloids, as we already know, are precip- itated by alkalies, their hydroxides, carbonates, and bicar- bonates; Fowler’s solution contains free potassium carbonate (potassium bicarbonate is used, but on being boiled becomes converted into carbonate) ; the pure alkaloid morphine pre- cipitates. A few drops of diluted HCl added to the arsenic solution, before it is mixed with the morphine solution, will prevent precipitation, because it will neutralize the potassium carbonate. 23, Antipyrini » gt. XxX Syr. Ipecac. 5 iiss Syr. Pron. Virgin. - Fe Aquae ad 3 ii S.: 3i4xa day. A flocculent precipitate is formed, due to the tannie acid of the wild cherry combining with the antipyrine. The latter is a synthetic base, behaving in most respects as the alkaloids do, which, as we saw before, are precipitated by tannic acid. Though the mixture might be dispensed with a ‘‘shake’’ label, it is better to call the physician’s attention to the fact, so that he may in the future substitute another syrup for that of wild cherry. 24. Antipyrini . gr. xl Spir. Aether’ 3 ss Spir. Frumenti 3 ss Syr. Tolutani .. Bi S.: Sig. 2h.