The principal product is quinine, the manufacture of which has acq~iired great importance, owing to its use as a specific against malaria.
In 1902 the state took up the sale of quinine at a low price, manufacturing it at the central military pharmaceutical laboratory at Turin.
Then a certain amount of immunity may be acquired by the systematic use of quinine.
Koch has suggested that the disinfection of malarial persons by quinine would have the desired effect, but other authorities of greater experience do not consider it practicable.
The suggested causes are (I) reduction of insects by drainage, (2) reduced population, (3) the use of quinine.
Quinine still remains the one specific. In serious cases it should not be given in solid form, but in solution by the stomach, rectum, or - better - hypodermically (Manson).
Euquinine is by some preferred to quinine, but it is more expensive.
Nucleogen and Aristochin have also been recommended instead of quinine.
Iron and quinine citrate is used as a bitter stomachic and tonic. In the blood citrates are oxidized into carbonates; they therefore act as remote alkalis, increasing the alkalinity of the blood and thereby the general rate of chemical change within the body.
His earlier work was mainly concerned with organic chemistry, and he published researches on picoline and its derivatives in 1876-78 and on quinine and its decomposition products in 1878-79.
Salicylates are the next safest to quinine of all antipyretics, whilst being much more powerful in all febrile states except malaria.
The drug is not a true specific, as quinine is for malaria, since it rarely, if ever, prevents the cardiac damage usually done by rheumatic fever; but it entirely removes the agonizing pain, shortly after its administration, and, an hour or two later, brings down the temperature to normal.
It often relieves neuralgia, especially when combined with caffeine and quinine.
As in the case of quinine, the administration of small doses of hydrobromic acid often relieve the milder symptoms.
There are many substances produced by plants which can be synthetically prepared by chemical means, but, as with quinine, the process involved is too costly to enable the synthetic product to compete with the natural product.
That quinine, chloroform, glycerin, alcohol, with others, had no attractive influence on them - negative chemiotaxis.
But the forests of Huanuco and Huamalios abound in species yielding the grey bark of commerce, which is rich in cinchonine, an alkaloid efficacious as a febrifuge, though inferior to quinine.
The suburbs of Sachsenhausen and Bockenheim have particularly developed considerable industrial activity, especially in publishing and printing, brewing and the manufacture of quinine.
substitution for quinine.
Devoting his evenings to private investigations in a rough laboratory fitted up at his home, Perkin was fired by some remarks of Hofmann's to undertake the artificial production of quinine.
the production of silk and wine, of coca and quinine; to promote forestry; to improve elementary and higher education - for all which purposes the Ministerio del Fomento is a potent engine; to encourage colonization; and, above all, to place the national credit on a sound basis.
Piperine, conine, atropine, belladonine, cocaine, hyoscyamine and nicotine have been already synthesized; the constitution of several others requires confirmation, while there remain many important alkaloids - quinine, morphine, strychnine, &c. - whose constitution remains unknown.
(3) Quinoline group. The alkaloids of the quina-barks: quinine, &c.; the strychnos bases: strychnine, brucine; and the veratrum alkaloids: veratrine, cevadine, &c.
The bitterness is imparted by such substances as bitter orange rind, gentian, rhubarb, quassia, cascarilla, angostura, quinine and cinchona.
The syrup of iron, quinine and strychnine is used as a tonic.
He also found that chickens that had been given meal moistened with quinine and placed upon glass slips banded black and yellow, afterwards refused to touch meal moistened with water and spread upon the same slips, although they had previously eaten it with readiness off plain coloured slips.
Other branches of industry include carpet-weaving at Deventer, the distillation of brandy, gin and liqueurs at Schiedam, Rotterdam and Amsterdam, and beer-brewing in most of the principal towns; shoe-making and leather-tanning in the Langstraat district of North Brabant; paper-making at Apeldoorn, on the Zaan, and in Limburg; the manufacture of earthenware and faience at Maastricht, the Hague and Delft, as well as at Utrecht, Purmerend and Makkum; clay pipes and stearine candles at Gouda; margarine at Osch; chocolate at Weesp and on the Zaan; mat-plaiting and broom-making at Genemuiden and Blokzyl; diamondcutting and the manufacture of quinine at Amsterdam; and the making of cigars and snuff at Eindhoven, Amsterdam, Utrecht, Kampen, &c. Shipbuilding is of no small importance in Holland, not only in the greater, but also in the smaller towns along the rivers and canals.
the summer is propagated by the mosquito (Anopheles claviger) marks a new epoch; the most diverse theories as to its origin had hitherto been propounded, but it is now possible to combat it on a definite plan, by draining the marshes, protecting the houses by fine mosquito-proof wire netting (for Anopheles is not active by day), improving the water supply, &c., while for those who have fever, quinine (now sold cheaply by the state) is a great specific. A great improvement is already apparent; and a law carried in 1903 for the Bonifica dell' Agro Romano compels the proprietors within a radius of some 6 m.
In the case of white people exposure to heat of itself frequently causes heat-stroke, but probably in almost all cases of heat hyperpyrexia amongst natives the malarial complication is the exciting cause and therefore with them quinine treatment is all-important.
The sulphate of quinine and the cinchona febrifuge thus produced are issued for the most part to medical officers in the various provinces, to gaols, and to the authorities of native states; but a large and increasing amount is disposed of in the form of 5-grain packets, costing a farthing each, through the medium of the post-offices.
In 1680 he was the constant victim of severe fevers, from which he recovered for a time through the use of quinine prescribed by an English physician.
The governors were directed to regulate religious instruction in secular schools, to prevent horse-stealing, to control subscriptions collected for the holy places in Palestine, to regulate the advertisements of medicines and the printing on cigarette papers, to examine the quality of quinine soap and overlook the cosmetics and other toilet articles - such as soap, starch, brillantine, tooth-brushes and insect-powder - provided by chemists.
Amongst other antipyretics, the most important are quinine, phenacetin and antifebrin.
When the attack is periodic the administration of a large dose of quinine two or three hours previous to the usual time of the seizure will often mitigate, and may even prevent the paroxysm.
The Bolivian product is of the best because of the high percentage of quinine sulphate which it yields.
In 1820 Pelletier and Caventou proved that the cinchonino of Gomez contained two alkaloids, which they named quinine and cinchonine.
For this reason those barks which, like C. Calisaya, C. officinalis, and C. Ledgeriana, contain but little colouring matter are preferred, the quinine being more easily extracted from them in a colourless form.
The sulphates of the alkaloids thus obtained are not equally soluble in water, and the quinine sulphate can be separated by fractional crystallization, being less soluble in water than the other sulphates.
Quinine of commerce is the neutral sulphate,C20H24N202 H2S04.8H20, which occurs in commerce in the form of very light slender white acicular crystals.
When prescribed it is generally rendered more soluble in water by the addition of dilute sulphuric acid or of citric acid, one drop of the former or 4ths of a grain of the latter being used for each grain of the quinine sulphate.
Quinine is precipitated from its solution by alkalis and their carbonates.
The acid solution of sulphate of quinine is fluorescent, especially when dilute; and it is laevo-rotatory.
This test answers with a solution containing only 1 part of quinine in 5000, or in a solution containing not more than part if bromine be used instead of chlorine.
By adding an alcoholic solution of iodine to a solution of the sulphate in acetic acid a compound known as herapathite, 4Qu 3H 2 SO 4.2HI Ie6H 2 O, is obtained, which possesses optical properties similar to those of tourmaline; it is soluble in Iwo parts of boiling water; and its sparing solubility in cold alcohol has been utilized for estimating quinine quantitatively.
The other alkaloids are distinguished from quinine thus: quinidine resembles quinine, but is dextro-rotatory, and the iodide is very insoluble in water; the solution of cinchonidine, which is laevo-rotatory, does not give the thalleoquin test, nor fluorescence; cinchonine resembles cinchonidine in these respects, but is dextrorotatory.
Commercial sulphate of quinine frequently contains from I tc 10% of cinchonidine sulphate, owing to the use of barks containing it.
The sulphate of cinchonidine is more soluble than that of quinine; and, when 1 part of quinine sulphate suspected to contain it is nearly dissolved in 24 parts of boiling water, the sulphate of quinine crystallizes out on' cooling, and the cinchonidine is found in the clear mother liquor, from which it can be precipitated by a solution of potassium and sodium tartrate.
Samples of quinine in which cinchonidine is present usually contain a smaller percentage of water than the pure sulphate.
Owing to its voluminous character as much as 18% of water may remain present in apparently dry samples of sulphate of quinine.
Sulphate of quinine manufactured from cuprea bark (Remijia pedunculata) may contain from -Do to.
90% of sulphate of homoquinine, which almost coincides in solubility with sulphate of quinine.
Homoquinine is decomposed on treatment with caustic soda into quinine and a new alkaloid, cupreine, in the proportion of 2 to 3.
Cupreine is soluble in a solution of caustic soda (differing in this respect from quinine), and therefore it is easy to prepare sulphate of quinine perfectly free from either homoquinine or cupreine.
In consequence of the high price of the alkaloid an attempt was made some years ago by the Government of India to manufacture from cinchona bark a cheap febrifuge which should represent the alkaloids contained in the bark and form a substitute for quinine.
A mixture of the cinchona alkaloids, consisting principally of cinchonidine sulphate, with smaller quantities of the sulphates of quinine and cinchonine, is sold under the name of "quinetum" at a cheaper rate than quinine.
The chemical constitution of quinine and the allied alkaloids is not definitely settled, although certain relationships are well established.
Thus quinine is methoxycinchonine or methylcupreine, cupreine being an oxycinchonine.
OH; cupreine = C19H20N2(OH)21 quinine =C19H20N2(OH) (OCH 3).
C9H6N C02H, whilst quinine gives quininic acid, C9H5(OCH3)(C02H).
The acid hydrochloride is the most valuable of all salts of quinine.
The sulphate of quinine used in medicine may contain up to 3% of cinchonidine, but should be free from cinchonine, quinidine and cupreine.
The syrupus ferri phosphatis cum quinina et strychnina (Easton's Syrup) contains IIths of a grain of quinine in each drachm, that is, in each dose.
Here the quinine acts as a bitter tonic. The tinctura quininae ammoniata or "ammoniated quinine" is made by mixing t 75 grains of quinine sulphate, 2 fluid oz.
The dose of 2 to drachm contains little more than a grain of quinine, the antipyretic action of which is negligible.
The small quantity of quinine it contains is conditioned by the solubility of the alkaloid, which is precipitated when this tincture is diluted with water.
Quinine has considerable powers as an .antiseptic, this term defined for some time as indicating the power to kill bacteria.
Whilst quinine possesses this power, however, it is far more potently lethal to a particular form of animal organism known as the plasmodium malariae.
Against the bacteria quinine is not at all an exceptionally powerful antiseptic, though more powerful than carbolic acid.
Quinine does not affect the unbroken skin, and cannot be absorbed from it, but it is slightly irritant to the pain-conducting nerves of a raw surface.
The first feature of the internal action of quinine is its intensely bitter taste.
In this sense alone quinine is a tonic. The hydrochloric acid of the gastric juice is stated to convert any salt of quinine into a chloride, and it seems probable that the absorption of quinine takes place mainly from the stomach, for when the drug reaches the alkaline secretions of the duodenum it is precipitated, and probably none of it is thereafter absorbed.
The greater part of a dose of quinine sulphate administered by the mouth may be recovered, as a rule, from the faeces, this being much the most wasteful method of giving quinine.
Quinine hydrochloride circulates in the alkaline blood without precipitation, probably owing to the presence of carbonic acid in the blood.
The action of quinine on the blood itself - quite apart from its action on malarial blood - is of great complexity and importance.
Like alcohol and prussic acid, quinine interferes with oxidation, so that oxyhaemoglobin is relatively unable to give up its oxygen to the tissues, the metabolism of which is therefore greatly modified.
This property is doubtless partly - though not wholly - explanatory of the antipyretic action of quinine.
Hence quinine stops the process of diapedesis or emigration of the leucocytes from the blood-vessels into the tissues, and if applied to the, extravascular spaces it arrests the leucocytic movements there.
The explanation that this influence on the leucocytes explained the favourable action of quinine on certain inflammatory processes no longer holds, since we know that the inflammatory conditions are of microbic origin, and that the movements of the leucocytes are not objectionable, but highly desirable as a means of defence against bacteria and their products.
Quinine, therefore, is not beneficial in inflammatory conditions as far as this particular property is concerned.
The action of quinine on the circulatory apparatus is not marked.
The action of quinine on the temperature is important, for it is the safest of all known antipyretics.
But when the temperature is raised, quinine will frequently lower it.
The action is not due to any influence on the thermic centres, nor to any production of diaphoresis, but to the influence of quinine upon the stability of oxyhaemoglobin.
Quinine was the first antipyretic used, and after the introduction of such preparations as antipyrin and acetanilide it may still be said to be the safest, though it is much less powerful.
In some of the lower vertebrates quinine reduces the activity of the spinal cord, but in the human species it appears to stimulate the nervous mechanism of the uterus under certain conditions, and it is therefore included under the class of oxytocic or ecbolic drugs.
Quinine is excreted in some degree by nearly all the glands of the body, but mainly by the kidneys.
The study of the urine is highly interesting in correlation with that of the influence of quinine upon the oxidising power of the blood, and upon the movements of the leucocytes.
The amount of urea, creatin, creatinin, sulphates and phosphates in the urine is diminished, clearly showing that quinine exerts an inhibitory influence over the metabolic processes of the body.
The supreme value of quinine is as a specific antidote to malaria, against which it also possesses a powerful prophylactic action.
Quinine is apparently powerless to kill the organism when it is in its reproductive phase.
There is therefore no purpose to be served by administering quinine during a malarial paroxysm.
The quinine may be given in a single large dose-30 grains of the sulphate.
An equally effective method, which may be combined with the above, is to give the quinine in so-grain doses of the acid hydrochloride every four hours between the attacks.
After a single full dose of quinine no parasites can as a rule be observed in the blood for several days.
The quinine treatment may be begun with success on the day following an attack.
Quinine is much less efficacious in the treatment of post-malarial symptoms, such as neuralgia and haematuria, when no parasites can be detected in the blood.
In such cases quinine is often inferior to arsenic.
Quinine is largely used as a bitter tonic in doses of about half a grain.
Quinine has some analgesic power, and is a safe and often efficient drug in the treatment of neuralgia, even when the patient has not had malaria.
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