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dc.contributor.authorMacgilchrist, Archibald Currieen
dc.date.accessioned2019-02-15T14:33:54Z
dc.date.available2019-02-15T14:33:54Z
dc.date.issued1911en
dc.identifier.urihttp://hdl.handle.net/1842/35018
dc.description.abstracten
dc.description.abstractThe administration of Quinine, although so old and well tried a remedy, is still beset with many difficulties and feelings of uncertainty on the part of the physician regarding the rapidity and certainty of action of a given dose of the alkaloid, by whichever channel that dose is administered. This is due mainly to our want of knowledge regarding the physical, chemical and, in particular, physiologico-chemical peculiarities of Quinine and its salts. The factors influencing the absorption of Quinine from the gastro-intestinal tract have been neglected ; and even the relative therapeutic or prophylactic value of the various methods of administration of Quinine is still unsettled.en
dc.description.abstractBy many it is assumed that Quinine is absorbed chiefly from the stomach, the intestines taking little or no part in the absorption. Malanin, in 1868, pointed out the insolubility of the compound formed by Quinine and bile acids, and took for granted that, when this alkaloid was administered by the mouth, as much of it as was not absorbed from the stomach became inert on coming in contact with bile in the intestines and was thus eliminated in the faeces. A similar action was ascribed to bile acids by Kerner. Lauder Brunton, on account of the precipitation from a mixture of Quinine and bile acids of this salt, which is sparingly soluble, except in an excess of bile, recommended clearing out the liver by administering an emetic and a cholagotrue purgative before giving Quinine in the treatment of malaria. According to Sollmann, Quinine is fairly readily absorbed from the stomach: Giemsa and Schaumann, however, have come to the conclusion that most of the Quinine given by the mouth is absorbed from the small intestine. Marshall states that most of the Quinine passes into the duodenum: and Dixon is of the opinion that after entering the duodenum Quinine is under ordinary circumstances absorbed rapidly; but, if there is excess of alkali in the duodenum, Quinine is precipitated, forming with the bile acids insoluble salts which are passed unchanged in the faeces.en
dc.description.abstractWhen there is so little agreement regarding the fate of Quinine in the gastro-intestinal tract, it is not surprising to find an explanation of the marked variations in the absorption of Quinine—so often encountered in clinical practice, sometimes even in the same individual and when using the same salt of this alkaloid—wanting, and the reason of the efficacy of a preparation like Warburg’s tincture still shrouded in mystery. Warburg’s tincture has been described as “ merely Quinine concealed in a farrago of inert substances.” To this description Maclean’s (Netley) reply was—“I have never seen a single dose of Quinine given alone to the extent of 9.5 grains sufficient to arrest an exacerbation of remittent fever, much less prevent its recurrence; while nothing is more common than to seethe same quantity of the alkaloid in Warburg’s tincture bring about such results.” According to Sollmann the substances— aloes, rhubarb, camphor, gentian and aromatic substances which are combined with the alkaloid in Warburg’s tincture, “probably aid in the absorption of the Quinine;” and Cushny states that they promote Quinine absorption by acting on the stomach and that capsicum and piperine have a similar reputation as adjuvants in Quinine treatment. The view expressed in the National Dispensatory is that Quinine absorption is hastened by the previous administration of purgatives, of which a combination of rhubarb and aloes acts best.en
dc.description.abstractRegarding the relative value of the various methods of Quinine administration, it will suffice in these introductory remarks to refer to only two—oral and hypodermic. Most authors of text-books of pharmacology and therapeutics assume that Quinine given by the hypodermic method is rapidly and effectively absorbed. Cushny recommends this mode of administration in cases of emergency; Sollmann states that by hypodermic injections, deep into the gluteal muscles, rapid action is secured; Binz is of the opinion that absorption is thorough and quick. Many clinicians have expressed similar views. Recent experiments and clinical observations, however, have cast doubt upon the orthodox belief that hypodermic injections of Quinine, as of other medicinal agents, mean more rapid and more concentrated action than is possible with administration by the mouth. In Italy and Germany attempts have been made to solve this problem by laboratory methods. Kleine, on finding a smaller percentage of Quinine eliminated in the mine when the alkaloid was injected subcutaneously than when given by the mouth, came to the conclusion that absorption was less in the former instance and that the hypodermic method was therefore of less therapeutic value than the oral. Mariani made an intramuscular injection into the leg of a rabbit, with a solution of .201 gramme of the bi-hydrochloride of Quinine in one cubic centimetre of water, and from the muscle of the rabbit which was killed seventeen hours after the injection he recovered .1 gramme of anhydrous Quinine or 66.5 percent, of the amount injected. The results of Giemsa and Schaumann agree with those of Kleine they found that after oral administration the amount of Quinine eliminated in the urine was 38.5 per cent, of the dose administered and that after hypodermic injection the amount eliminated was only 19.2 per cent; but they regard this difference in the elimination of Quinine as due not to less absorption, but to a greater destruction of Quinine in the body when administered by hypodermic injection than when given by the mouth. Krom the clinical aspect, the subject has been investigated principally in India. Smythe states that Quinine injected hypodermically is slowly absorbed and is eliminated in the urine for many weeks after administration; and that 20 grains injected into the flanks will protect an individual from malaria for the following month at least. According to Megaw the temperature of patients suffering from malaria takes about twelve hours longer in coming to normal when treatment is by hypodermic injections (bi-hydrochloride of Quinine in doses of 10 grains) than when Quinine is given by the mouth, and consequently that absorption is slower from the subcutaneous connective tissue than from the mucous membrane of the stomach. Scott regards the hypodermic method (intramuscular) as of no special value in the treatment of acute cases of malarial fever, owing to slowness of absorption; but he considers this method particularly useful as a preventive of frequently recurring attacks of ague.en
dc.description.abstractThe authors of the National Dispensatory acknowledge that the tendency of hypodermic injections to produce “pain, inflammation, gangrene and even fatal tetanus more than counterbalances the advantages of facility of administration and promptness of effect” and recommend that this method of administration should be restricted to cases in which delay would be dangerous. The importance of determining whether or not this “promptness of effect” is really obtained by the hypodermic method is obvious.en
dc.description.abstractIn an endeavour to throw some light on these debated points regarding the absorption of Quinine, this work has been undertaken. The alkaloid and its salts employed in the various experiments were obtained direct from Merck (Darmstadt) and therefore in unopened bottles.en
dc.publisherThe University of Edinburghen
dc.relation.ispartofAnnexe Thesis Digitisation Project 2019 Block 22en
dc.relation.isreferencedbyen
dc.titleQuinine and its salts: their solubility and absorbabilityen
dc.typeThesis or Dissertationen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnameDSc Doctor of Scienceen


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