Chapter XXIX: Part VI: Alkaloids and Poisonous Vegetable Principles Separated for the (3)

§ 343. =Detection of Aniline.=--Aniline is easily separated and
detected. Organic fluids are alkalised by a solution of potash, and
distilled. The organs, finely divided, are extracted with water
acidulated with sulphuric acid, the fluid filtered, and then
alkalised and distilled. The distillate is shaken up with ether, the
ether separated and allowed to evaporate spontaneously. Any aniline
will be in the residue left after evaporation of the ether, and may
be identified by the following tests:--An aqueous solution of
aniline or its salts is coloured blue by a little chloride of lime
or hypochlorite of soda; later on the mixture becomes red. The blue
colour has an absorption band, when examined spectroscopically,
extending from W.L. 656 to 560, and therefore in the red and yellow
from Fraunhofer’s line C, and overlapping D. Another test for
aniline is the addition of kairine, hydrochloric acid, and sodium
nitrite, which strikes a blue colour.

III.--The Opium Group of Alkaloids.

§ 344. =General Composition.=--Opium contains a larger number of basic substances than any plant known. The list reaches at present to 18 or 19 nitrogenised bases, and almost each year there have been additions. Some of these alkaloids exist in very small proportion, and have been little studied. Morphine and narcotine are those which, alone, are toxicologically important. Opium is a gummy mass, consisting of the juice of the incised unripe fruit of the _Papaver somniferum_ hardened in the air. The following is a nearly complete list of the constituents which have been found in opium:--

Morphine, C₁₇H₁₉NO₃.
Narcotine, C₂₂H₂₃NO₇.
Narceine, C₂₃H₂₉NO₉.
Apomorphine, C₁₇H₁₇NO₂ } By dehydration of morphine and codeine
Apocodeine, C₁₈H₁₉NO₂ } respectively.
Pseudomorphine, C₁₇H₁₉NO₄.
Codamine, C₂₀H₂₅NO₄.
Ladanine, C₂₀H₂₅NO₄.
Ladanosine, C₂₁H₂₇NO₄.
Protapine, C₂₀H₁₉NO₅.
Cryptopine, C₂₁H₂₃NO₅.
Lanthopine, C₂₃H₂₅NO₄.
Hydrocotarnine, C₁₂H₁₅NO₃.
Opianine, C₂₁H₂₁NO₇.
Cnoscopine, C₃₄H₃₆N₂O₁₁.
Rhœadine, C₂₀H₂₁NO₇.
Codeine, C₁₈H₂₁NO₃.
Thebaine, C₁₉H₂₁NO₃.
Papaverine, C₂₀H₂₁NO₄.
Meconidine, C₂₁H₂₃NO₄.
Meconin, C₁₀H₁₀O₄.
Meconic acid, C₇H₄O₇.
Thebolactic acid.
Fat.
Resin.
Caoutchouc.
Gummy matters--Vegetable mucus.
Ash, containing the usual constituents.

The various opiums differ, the one from the other, in the percentages of alkaloids, so that only a very general statement of the mean composition of opium can be made. The following statement may, however, be accepted as fairly representative of these differences:--

Per cent.
Morphine, 6 to 15
Narcotine, 4 to 8
Other alkaloids, 5 to 2
Meconin, Under 1
Meconic acid, 3 to 8
Peculiar resin and caoutchouc, 5 to 10
Fat, 1 to 4
Gum and soluble humoid acid matters, 40 to 50
Insoluble matters and mucus, 18 to 20
Ash, 4 to 8
Water, 8 to 30

The general results of the analysis of 12 samples of Turkey opium, purchased by Mr. Bott,[369] from leading druggists in London, Dublin, and Edinburgh, are as follows:--

[369] _Year Book of Pharmacy_, 1876.

=Water.=--Highest, 31·2; lowest, 18·4; mean, 22·4 per cent.

=Insoluble Residue.=--Highest, 47·9; lowest, 25·45; mean, 32·48 per cent.

=Aqueous Extract.=--Highest, 56·15; lowest, 20·90; mean, 45·90 per cent.

=Crude Morphine= (containing about 7/10 of pure morphine).--Highest, 12·30; lowest, 6·76; mean, 9·92 per cent., which equals 12·3 per cent. of the dried drug.

=Persian Opium=, examined in the same way, varied in crude morphine from 2·1 to 8·5 per cent.; Malwa, from 5·88 to 7·30. In 18 samples of different kinds of opium, the mean percentage of crude morphine was 8·88 per cent. (11 per cent. of the dried opium). According to Guibourt, Smyrna opium, dried at 100°, yields 11·7 to 21·46 per cent., the mean being 12 to 14 per cent.; Egyptian, from 5·8 to 12 per cent.; Persian, 11·37 per cent. In East Indian Patna opium, for medical use, he found 7·72; in a sample used for smoking, 5·27 per cent.; in Algerian opium, 12·1 per cent.; in French opium, 14·8 to 22·9 per cent.

§ 345. =Action of Solvents on Opium.=--The action of various solvents on opium has been more especially studied by several scientists who are engaged in the extraction of the alkaloids.

=Water= dissolves nearly everything except resin, caoutchouc, and woody fibre. Free morphine would be left insoluble; but it seems always to be combined with meconic and acetic acids. The solubility of free narcotine in water is extremely small.

=Alcohol= dissolves resin and caoutchouc, and all the alkaloids and their combinations, with meconic acid, &c.

=Amylic Alcohol= dissolves all the alkaloids, if they are in a free state, and it also takes up a little of the resin.

=Ether, Benzene, and Carbon Sulphide= do not dissolve the resin, and only slightly morphine, if free; but they dissolve the other free alkaloids as well as caoutchouc.

=Acids= dissolve all the alkaloids and the resin.

=Fixed Alkalies=, in excess, dissolve in part resin; they also dissolve morphine freely; narcotine remains insoluble.

=Lime Water= dissolves morphine, but is a solvent for narcotine only in presence of morphine.

=Ammonia= dissolves only traces of morphine; but narceine and codeine readily. It does not dissolve the other alkaloids, nor does it dissolve the resin.

§ 346. =Assay of Opium.=--The following processes may be described:--

=Process of Teschemacher and Smith.=--This process, with a few modifications, is as follows:--10 grms. of opium are as completely exhausted with proof spirit at a boiling temperature as possible. The resulting alcoholic extract is treated with a few drops of ammonium oxalate solution, and the solution is almost neutralised with ammonia. The solution is concentrated to one-third, cooled, and filtered. The filtrate is farther concentrated to 5 c.c., and transferred to a small flask, it is washed into this flask by 4 c.c. of water, and 3 c.c. of 90 per cent. alcohol; next 2 c.c. solution of ammonia (sp. gr. 0·960) and 25 c.c. of dry ether are added. The flask is corked, shaken, and then allowed to rest over-night.

The ether is decanted as completely as possible. Two filter papers are taken and counterpoised--that is to say, they are made precisely the same weight. The filters are placed one inside the other, and the precipitate collected on the inner one; the precipitate is washed with morphinated water--that is to say, water in which morphine has been digested for some days. The filter papers with their contents are washed with benzene and dried, the outer paper put on the pan of the balance carrying the weights, and the inner filter with the precipitate weighed. The precipitate is now digested with a known volume of decinormal acid, and then the excess of acid ascertained by titration with decinormal alkali, using either litmus or methyl orange; each c.c. of decinormal acid is equal to 30·3 mgrms. of morphine.[370]

[370] _Pharm. Journal_, xix. 45, 82; xxii. 746. Wright and Farr, _Chemist and Druggist_, 1893, i. 78.

=Dott’s Process.=--Dott has recently proposed a new process, which he states has given good results. The process is as follows:--10 grammes of powdered opium are digested with 25 c.c. water; 1·8 gramme barium chloride dissolved in about 12 c.c. water is then added, the solution made up to 50 c.c., well mixed, and after a short time filtered. 22 c.c. (representing 5 grammes opium) are mixed with dilute sulphuric acid in quantity just sufficient to precipitate the barium. About 1 c.c. is required, and the solution should be warmed to cause the precipitate to subside, and the solution to filter clear. To this filtered solution a little dilute ammonia, about 0·5 c.c. is added to neutralise the free acid, and the solution concentrated to 6 or 7 c.c., and allowed to cool. 1 c.c. spirit and 1 c.c. ether are then added, and next ammonia in slight excess. The ammonia should be added gradually until there is no further precipitation, and a perceptible odour of ammonia remains after well stirring and breaking down any lumps with the stirring rod. After three hours the precipitate is collected on counterpoised filters and washed. Before filtering, it should be noted that the solution has a faint odour of ammonia: if not, one or two drops of ammonia solution should be added. The dried precipitate is washed with benzene or chloroform, dried, and weighed. It is then titrated with _n_/10 acid, until the morphine is neutralised, as indicated by the solution reddening litmus paper.[371]

[371] Other methods of opium assay have been published: see Mr. A. B. Prescott’s method (_Proceedings of Amer. Pharm. Assoc._, 1878); Allen (_Commercial Org. Analysis_, vol. ii. p. 473); E. R. Squibb’s modification of Flückiger’s method (_Pharm. Journ._ (3), xii. p. 724); a rapid mode of opium assay, MM. Portes and Lanjlois (_Journ. de Pharm. et de Chim._, Nov. 1881); _Year Book of Pharmacy_, 1882.

To the above may be added--(1.) _Schacht’s Method._--5 to 10 grms. of dry, finely-powdered opium are digested with sufficient distilled water to make a thin pulp. After twenty-four hours the whole is thrown on a weighed filter, and washed until the washings are almost colourless and tasteless. The portion insoluble in water is dried at 100° and weighed; in good opium this should not exceed 40 per cent. The filtrate is evaporated until it is about one-fifth of the weight of the opium taken originally; cooled, filtered, and treated with pure animal charcoal, until the dark brown colour is changed into a brownish-yellow. The liquid is then refiltered, precipitated with a slight excess of ammonia, allowed to stand in an open vessel until all odour of ammonia disappears, and at the same time frequently stirred, in order that the precipitate may not become crystalline--a form which is always more difficult to purify. The precipitate is now collected on a tared filter, washed, dried, and weighed. With an opium containing 10 per cent. of morphine, its weight is usually 14 per cent. A portion of the precipitate is then detached from the filter, weighed, and exhausted, first with ether, and afterwards with boiling alcohol (0·81 specific gravity). Being thus purified from narcotine, and containing a little colouring-matter only, it may now be dried and weighed, and the amount of morphine calculated, on the whole, from the data obtained.

(2.) _Fleury_ has proposed a titration by oxalic acid as follows:--2 grms. of the powdered opium are macerated a few hours with 8 c.c. of aqueous oxalate of ammonia, brought on a filter, and washed with 5 c.c. of water. To the filtrate an equal volume of 80 per cent. alcohol and ammonia to alkaline reaction is added; and, after standing twenty-four hours in a closed flask, it is filtered, and the flask rinsed out with some c.c. of 40 per cent. alcohol. The filter, with its contents, after drying, is placed in the same flask (which should not be cleansed), a few drops of alcoholic logwood solution are added, with an excess of oxalic acid solution of known strength, the whole being made up to 100 c.c. This is divided into two parts, and the excess of acid titrated back with diluted soda-lye. If the oxalic acid solution is of the strength of 4·42 grms. to the litre, every c.c. of the oxalic acid solution which has become bound up with morphine, corresponds to 0·02 grm. of morphine.

§ 347. =Medicinal and other Preparations of Opium.=--The chief mixtures, pills, and other forms, officinal and non-officinal, in which opium may be met with, are as follows:--

(1.) OFFICINAL.

=Compound Tincture of Camphor=, P. B. (Paregoric).--Opium, camphor, benzoic acid, oil of anise, and proof spirit: the opium is in the proportion of about 0·4 per cent., or 1 grain of opium in 240 minims.

=Ammoniated Tincture of Opium= (Scotch paregoric).--Strong solution of ammonia, rectified spirit, opium, oil of anise, saffron, and benzoic acid. Nearly 1 per cent. or 1 grain of opium in every 96 minims.

=The Compound Powder of Kino=, P. B.
Opium, 5 per cent.
Cinnamon, 20 „
Kino, 75 „

=The Compound Powder of Opium=, P. B.
Opium, 10·00 per cent.
Black Pepper, 13·33 „
Ginger, 33·33 „
Caraway Fruit, 40·00 „
Tragacanth, 3·33 „

=Pill of Lead and Opium=, P. B.
Acetate of Lead, 75·0 per cent.
Opium, 12·5 „
Confection of Roses, 12·5 „

=Tincture of Opium= (=Laudanum=).--Opium and proof spirit. One grain of opium in 14·8 min.--that is, about 6·7 parts by weight in 100 by measure.

The amount of opium actually contained in laudanum has been investigated by Mr. Woodland,[372] from fourteen samples purchased from London and provincial chemists. The highest percentage of extract was 5·01, the lowest 3·21, the mean being 4·24; the highest percentage of morphine was ·70 per cent., the lowest ·32, the mean being ·51 per cent. It is, therefore, clear that laudanum is a liquid of very uncertain strength.

[372] _Year Book of Pharmacy_, 1882.

=Aromatic Powder of Chalk and Opium.=--Opium 2·5 per cent., the rest of the constituents being cinnamon, nutmeg, saffron, cloves, cardamoms, and sugar.

=Compound Powder of Ipecacuanha= (Dover’s Powder).

Opium, 10 per cent.
Ipecacuanha, 10 „
Sulphate of Potash, 80 „

=Confection of Opium= (=Confectio opii=) is composed of syrup and compound powder of opium; according to its formula, it contains 2·4 per cent. of opium by weight.

=Extract of Opium= contains the solid constituents capable of extraction by water; it should contain 20 per cent. of morphine, and is therefore about double the strength of dry powdered opium.

=Liquid Extract of Opium= has been also examined by Mr. Woodland:[373] ten samples yielded as a mean 3·95 per cent. of dry extract, the highest number being 4·92 per cent., the lowest 3·02. The mean percentage of morphine was ·28 per cent., the highest amount being ·37, and the lowest ·19 per cent.

[373] _Op. cit._

=Liniment of Opium= is composed of equal parts of laudanum and soap liniment; it should contain about 0·0375 per cent. morphine.

=The Compound Soap-pill= is made of soap and opium, one part of opium in every 5·5 of the mass--_i.e._, about 18 per cent.

=Ipecacuanha and Morphine Lozenges=, as the last, with the addition of ipecacuanha; each lozenge contains 1/36 grain (1·8 mgrms.) morphine hydrochlorate, 1/12 grain (5·4 mgrms.) ipecacuanha.

=Morphia Suppositories= are made with hydrochlorate of morphine, benzoated lard, white wax, and oil of theobroma; each suppository contains ½ grain (32·4 mgrms.) of morphine salt.

=Opium Lozenges= are composed of opium extract, tincture of tolu, sugar, gum, extract of liquorice, and water. Each lozenge contains 1/10 grain (6·4 mgrms.) of extract of opium, or about 1/50 grain (1·3 mgrm.) morphine.

=The Ointment of Galls and Opium= contains one part of opium in 14·75 parts of the ointment--_i.e._, opium 6·7 per cent.

=Opium Wine=, P. B.--Sherry, opium extract, cinnamon, and cloves. About 5 of opium extract by weight in 100 parts by measure (22 grains to the ounce).

=Solutions of Morphine=, both of the acetate and hydrochlorate, P. B., are made with a little free acid, and with rectified spirit. The strength of each is half a grain in each fluid drachm (·0324 grm. in 3·549), or ·91 part by weight in 100 by measure.

=Solution of Bimeconate of Morphine.=--One fluid oz. contains 5½ grains of bimeconate of morphine.

=Morphia Lozenges= are made with the same accessories as opium lozenges, substituting morphine for opium; each lozenge contains 1/36 grain of hydrochlorate of morphia (1·8 mgrm.).

=Syrup of Poppies.=--The ordinary syrup of poppies is sweetened laudanum. It should, however, be what it is described--viz., a syrup of poppy-heads. As such, it is said to contain one grain of extract of opium to the ounce.

(2.) PATENT AND OTHER NON-OFFICINAL PREPARATIONS OF OPIUM.

=Godfrey’s Cordial= is made on rather a large scale, and is variable
in strength and composition. It usually contains about 1½ grains of
opium in each fluid ounce,[374] and, as other constituents:
sassafras, molasses or treacle, rectified spirit, and various
flavouring ingredients, especially ginger, cloves, and coriander;
aniseed and caraways may also be detected.

[374] If made according to Dr. Paris’ formula, 1⅙ grains in an ounce.

=Grinrod’s Remedy for Spasms= consists of hydrochlorate of morphine,
spirit of sal-volatile, ether, and camphor julep; strength, 1 grain
of the hydrochlorate in every 6 ounces.

=Lemaurier’s Odontalgic Essence= is acetate of morphine dissolved in
cherry-laurel water; strength, 1 grain to the ounce.

=Nepenthe= is a preparation very similar to _Liq. Opii sedativ._,
and is of about the same strength as laudanum.[375]

[375] It may be regarded as a purified alcoholic solution of meconate of morphia, with a little excess of acid, and of about the same strength as laudanum.--_Taylor._

=Black Drop= (known also by various names, such as Armstrong’s Black
Drop) is essentially an acetic acid solution of the constituents of
opium. It is usually considered to be of four times the strength of
laudanum. The wholesale receipt for it is: Laudanum, 1 oz., and
distilled vinegar 1 quart, digested for a fortnight. The original
formula proposed by the Quaker doctor of Durham, Edward Tunstall,
is--Opium, sliced, ½ lb.; good verjuice,[376] 3 pints; and nutmeg,
1½ oz.; boiled down to a syrup thickness; ¼ lb. of sugar and 2
teaspoonfuls of yeast are then added. The whole is set in a warm
place for six or eight weeks, after which it is evaporated in the
open air until it becomes of the consistence of a syrup. It is
lastly decanted and filtered, a little sugar is added, and the
liquid made up to 2 pints.

[376] Verjuice is the juice of the wild crab.

=“Nurse’s Drops”= seem to be composed of oil of caraway and
laudanum.

=Powell’s Balsam of Aniseed=, according to evidence in the case of
_Pharmaceutical Society v. Armson_ (_Pharm. Journ._, 1894), contains
in every oz. 1/10 grain of morphine.

=Dalby’s Carminative=--

Carbonate of magnesia, 40 grains.
Tincture of castor, and compound tincture of cardamoms,
of each 15 drops.
Laudanum, 5 „
Oil of aniseed, 3 „
Oil of nutmeg, 2 „
Oil of peppermint, 1 „
Peppermint water, 2 fl. ounces

Dose, from a half to one teaspoonful. Another recipe has no
laudanum, but instead syrup of poppies.

=Chlorodyne=--Brown’s Chlorodyne is composed of--

Chloroform, 6 drachms.
Chloric ether, 1 „
Tincture of capsicum, ½ „
Hydrochlorate of morphine, 8 grains.
Scheele’s prussic acid, 12 drops
Tincture of Indian hemp, 1 drachm.
Treacle, 1 „

=Atkinson’s Infant Preserver=--

Carbonate of magnesia, 6 drachms.
White sugar, 2 ounces
Oil of aniseed, 20 drops.
Spirit of sal-volatile, 2½ drachms.
Laudanum, 1 „
Syrup of saffron, 1 ounce.
Caraway water, to make up, 1 pint.

=Boerhave’s Odontalgic Essence=--

Opium, ½ drachm.
Oil of cloves, 2 „
Powdered camphor, 5 „
Rectified spirit, 1½ fl. ounce.

§ 348. =Statistics.=--During the ten years 1883-1892 no less than 1424 deaths in England and Wales were attributed to some form or other of opium or its active constituents; 45 of these deaths were ascribed to various forms of soothing syrup or to patent medicines containing opium or morphine; 876 were due to accident or negligence; 497 were suicidal and 6 were homicidal deaths. The age and sex distribution of the deaths ascribed to accident and those ascribed to suicide are detailed in the following tabular statement:--

DEATHS IN ENGLAND AND WALES DURING THE TEN YEARS 1883-1892 FROM OPIUM, LAUDANUM, MORPHINE, &c.

ACCIDENT.

Ages, 0-1 1-5 5-15 15-25 25-65 65 and Total
above
Males, 72 27 1 16 302 85 503
Females, 50 23 4 21 189 86 373
--------------------------------------------
Total, 122 50 5 37 491 171 876
--------------------------------------------

SUICIDE.

Ages, 5-15 15-25 25-65 65 and Total
above
Males, 1 26 269 34 330
Females, ... 24 126 17 167
----------------------------------
Total, 1 50 395 51 497
----------------------------------

Of European countries, England has the greatest proportional number of opium poisonings. In France, opium or morphine poisoning accounts for about 1 per cent. of the whole; and Denmark, Sweden, Switzerland, Germany, all give very small proportional numbers; arsenic, phosphorus, and the acids taking the place of opiates. The more considerable mortality arises, in great measure, from the pernicious practice--both of the hard-working English mother and of the baby-farmer--of giving infants various forms of opium sold under the name of “_soothing syrups_,” “_infants’ friends_,” “_infants’ preservatives_,” “_nurses’ drops_” and the like, to allay restlessness, and to keep them during the greater part of their existence asleep. Another fertile cause of accidental poisoning is mistakes in dispensing; but these mistakes seem to happen more frequently on the Continent than in England. This is in some degree due to the decimal system, which has its dangers as well as its advantages, _e.g._:--A physician ordered ·5 decigrm. of morphine acetate in a mixture for a child, but omitted the decimal point, and the apothecary, therefore, gave ten times the dose desired, with fatal effect. Again, morphine hydrochlorate, acetate, and similar soluble salts are liable to be mistaken for other white powders, and in this way unfortunate accidents have occurred--accidents that, with proper dispensing arrangements, should be impossible.

§ 349. =Poisoning of Children by Opium.=--The drugging of children by opium--sometimes with a view to destroy life, sometimes merely for the sake of the continual narcotism of the infant--is especially rife in India.[377] A little solid opium is applied to the roof of the mouth, or smeared on the tongue, and some Indian mothers have been known to plaster the nipples with opium, so that the child imbibes it with the milk. Europeans, again and again, have discovered the native nurses administering opiates to the infants under their care, and it is feared that in many cases detection is avoided.

[377] See Dr. Chevers’s _Jurisprudence_, 3rd ed., 232 _et seq._

The ignorant use of poppy-tea has frequently caused the death of young children; thus in 1875 an inquest was held at Chelsea on the body of a little boy two years and a half old. He had been suffering from whooping-cough and enlargement of the bowels, and poppy-tea was by the advice of a neighbour given to him. Two poppy-heads were used in making a quart of tea, and the boy, after drinking a great portion of it, fell into a deep sleep, and died with all the symptoms of narcotic poisoning.

§ 350. =Doses of Opium and Morphia.=--Opium in the solid state is prescribed for adults in quantities not exceeding 3 grains, the usual dose being from 16·2 mgrms. to 64·8 mgrms. (¼ to 1 grain). The extract of opium is given in exactly the same proportions (special circumstances, such as the habitual use of opium, excepted); the dose of all the compounds of opium is mainly regulated by the proportion of opium contained in them.

The dose for children (who bear opium ill) is usually very small; single drops of laudanum are given to infants at the breast, and the dose cautiously increased according to age. Most practitioners would consider half a grain a very full dose, and, in cases requiring it, would seldom prescribe at first more than 1/16 to ¼ grain.

The dose of solid opium for a horse is from 1·77 grm. to 7·08 grms. (½ drachm to 2 drachms); in extreme cases, however, 4 drachms (14·16 grms.) have been given.

The dose for large cattle is from ·648 grm. to 3·88 grms. (10 to 60 grains); for calves, ·648 grm. (10 grains); for dogs it is greatly regulated by the size of the animal, 16·2 to 129·6 mgrms. (¼ grain to 2 grains).

=Fatal Dose.=--Cases are recorded of infants dying from extremely small doses of opium, _e.g._, ·7, 4·3, and 8·1 mgrms. (1/90, 1/15, and ⅛ of a grain); but in such instances one cannot help suspecting some mistake. It may, however, be freely conceded that a very small quantity might be fatal to infants, and that 3 mgrms. given to a child under one year would probably develop serious symptoms.

The smallest dose of solid opium known to have proved fatal to adults was equal to 259 mgrms. (4 grains) of crude opium (_Taylor_), and the smallest dose of the tincture (laudanum), 7·0 c.c. (2 drachms), (_Taylor_); the latter is, however, as already shown, uncertain in its composition.

A dangerous dose (save under special circumstances) is:--For a horse, 14·17 grms. (4 drachms); for cattle, 7·04 grms. (2 drachms); for a dog of the size and strength of a foxhound, 204 mgrms. (3 grains).

Enormous and otherwise fatal doses may be taken under certain conditions by persons who are not opium-eaters. I have seen 13 cgrms. (2 grains) of morphine acetate injected hypodermically in a strong man suffering from rabies with but little effect. Tetanus, strychnine, convulsions, and excessive pain all decrease the sensibility of the nervous system to opium.

§ 351. =General Method for the Detection of Opium.=--It is usually laid down in forensic works that, where poisoning by opium is suspected, it is sufficient to detect the presence of meconic acid in order to establish that of opium. In a case of adult poisoning there is generally substance enough available to obtain one or more alkaloids, and the presence of opium may, without a reasonable doubt, be proved, if meconic acid (as well as either morphine, narcotine, thebaine, or other opium alkaloid) has been detected. Pills containing either solid opium or the tincture usually betray the presence of the drug by the odour, and in such a case there can be no possible difficulty in isolating morphine and meconic acid, with probably one or two other alkaloids. The method of extraction from organic fluids is the same as before described, but it may, of course, be modified for any special purpose. If opium, or a preparation of opium, be submitted to Dragendorff’s process (see p. 242), the following is a sketch of the chief points to be noticed.

If the solution is _acid_--

(1.) =Benzene= mainly extracts _meconin_, which dissolves in sulphuric acid very gradually (in twenty-four to forty-eight hours), with a green colour passing into red. Meconin has no alkaloidal reaction.

(2.) =Amyl alcohol= dissolves small quantities of _meconic acid_, identified by striking a blood-red colour with ferric chloride.

If now the amyl alcohol is removed with the aid of petroleum ether, and the fluid made alkaline by ammonia--

(1.) =Benzene= extracts _narcotine_, _codeine_, and _thebaine_. On evaporation of the benzene the alkaloidal residue may be dissolved in water, acidified with sulphuric acid, and after filtration, on adding ammonia _in excess_, _thebaine and narcotine_ are precipitated, _codeine_ remaining in solution. The dried precipitate, if it contain thebaine, becomes blood-red when treated with cold concentrated sulphuric acid, while narcotine is shown by a violet colour developing gradually when the substance is dissolved in dilute sulphuric acid 1 : 5, and gently warmed. The codeine in the ammoniacal solution can be recovered by shaking up with benzene, and recognised by the red colour which the solid substance gives when treated with a little sugar and sulphuric acid.

(2.) =Chloroform= especially dissolves the _narceine_, which, on evaporation of the chloroform, may be identified by its general characters, and by its solution in Fröhde’s reagent becoming a beautiful blue colour. Small quantities of morphine may be extracted with codeine.

(3.) =Amyl alcohol= extracts from the alkaline solution morphine, identified by its physical characters, by its forming a crystalline precipitate with iodine and hydriodic acid, and the reaction with iodic acid to be described.

§ 352. =Morphine= (C₁₇H₁₇NO(OH)₂ + H₂O).--Morphine occurs in commerce as a white powder, sp. gr. 1·205, usually in the form of more or less perfect six-sided prisms, but sometimes in that of white silky needles. When heated in the subliming cell (described at pp. 257-8), faint nebulæ, resolved by high microscopic powers into minute dots, appear on the upper disc at 150°. As the temperature is raised the spots become coarser, and at 188° distinct crystals may be obtained, the best being formed at nearly 200°, at which temperature morphine begins distinctly to brown, melt, and carbonise. At temperatures below 188°, instead of minute dots, the sublimate may consist of white circular spots or foliated patterns. One part of morphine, according to P. Chastaing, is soluble at a temperature of 3° in 33,333 parts of water; at 22°, in 4545 parts; at 42°, 4280; and at 100°, 4562. It is scarcely soluble in ether or benzene. Absolute alcohol, according to Pettenkofer, dissolves in the cold one-fortieth of its weight; boiling, one-thirtieth. Amyl alcohol, in the cold, dissolves one-fourth per cent., and still more if the alkaloid be thrown out of an aqueous acid solution by ammonia in the presence of amyl alcohol; for under such circumstances the morphine has no time to become crystalline. According to Schlimpert, 1 part of morphine requires 60 of chloroform for solution; according to Pettenkofer, 175.

Morphine is easily soluble in dilute acids, as well as in solutions of the caustic alkalies and alkaline earths; carbonated alkalies and chloride of ammonium also dissolve small quantities. The acid watery, and the alcoholic solutions, turn the plane of polarisation to the left; for sulphuric, nitric, and hydrochloric acids [α]_r_ = 89·8°; in alkaline solution the polarisation is less, [α]_r_ = 45·22°. It is alkaline in reaction, neutralising acids fully; and, in fact, a convenient method of titrating morphine is by the use of a centinormal sulphuric acid--each c.c. equals 2·85 mgrms. of anhydrous morphine.

§ 353. The salts of morphine are for the most part crystalline, and are all bitter, neutral, and poisonous. They are insoluble in amylic alcohol, ether, chloroform, benzene, or petroleum ether.

=Morphine meconate= is one of the most soluble of the morphine salts; it is freely soluble in water. Of all salts this is most suitable for subcutaneous injection; it is the form in which the alkaloid exists in opium.

=Morphine hydrochlorate= (C₁₇H₁₉NO₃HCl) crystallises in silky fibres; it is readily soluble in alcohol, and is soluble in cold, more freely in boiling water. The purest morphine hydrochlorate is colourless, but that which is most frequently met with in commerce is fawn or buff-coloured.

=Morphine acetate= is a crystallisable salt, soluble in water or alcohol; it is in part decomposed by boiling the aqueous solution, some of the acetic acid escaping.

=Morphine Tartrates.=--These are readily soluble salts, and it is important to note that the morphine might escape detection, if the expert trusted alone to the usual test of an alkaloidal salt giving a precipitate when the solution is alkalised by the fixed or volatile alkalies; for the tartrates of morphine do not give this reaction, nor do they give any precipitate with calcic chloride. By adding a solution of potassium acetate in spirit, and also alcohol and a little acetic acid to the concentrated solution, the tartrate is decomposed, and acid tartrate of potassium is precipitated in the insoluble form; the morphine in the form of acetate remains in solution, and then gives the usual reactions.

The solubility of morphine salts in water and alcohol has been investigated by Mr. J. U. Lloyd. His results are as follows:--

=Morphine Acetate.=

11·70 parts of water by weight at 15·0° dissolve 1 part of morphine
acetate.
61·5 parts of water by weight at 100° dissolve 1 part of morphine
acetate.
68·30 parts of alcohol by weight (·820 specific gravity) at 15·0°
dissolve 1 part of morphine acetate.
13·30 parts of alcohol by weight (·820 specific gravity) at 100°
dissolve 1 part of morphine acetate.

=Morphine Hydrochlorate.=

23·40 parts of water dissolve at 15° 1 morphine hydrochlorate.
·51 part of water dissolves at 100° 1 morphine hydrochlorate.
62·70 parts of alcohol (·820 specific gravity) dissolve at 15° 1
morphine hydrochlorate.
30·80 parts of alcohol (·820 specific gravity) dissolve at 100° 1
morphine hydrochlorate.

=Morphine Sulphate.=

21·60 parts of water at 15° dissolve 1 morphine sulphate.
·75 part of water at 100° dissolves 1 morphine sulphate.
701·5 parts of alcohol (·820) at 15° dissolve 1 morphine sulphate.
144·00 parts of alcohol (·820) at 100° dissolve 1 morphine sulphate.

§ 354. =Constitution of Morphine.=--The chief facts bearing on the constitution of morphine are as follows:--

It certainly contains two hydroxyl groups, because by the action of acetic anhydride, acetyl morphine and diacetyl morphine, C₁₇H₁₈(CH₃CO)NO₃ and C₁₇H₁₇(CH₃CO)₂NO₃ are produced. The formation of the monomethyl ether of morphine (codeine), C₁₇H₁₇(OH)(OCH₃)NO, is also a testimony to the existence of hydroxyl groups. One of the hydroxyl groups has phenolic functions, the other alcoholic functions. By suitable oxidation morphine yields trinitrophenol (picric acid), and by fusion with an alkali, protocatechuic acid; both of these reactions suggest a benzene ring. On distilling with zinc dust phenanthrene, pyridine, pyrrol, trimethylamine, and ammonia are formed; evidence of a pyridine nucleus. If morphine is mixed with 10 to 15 times its weight of a 20 per cent. solution of potash, and heated at 180° for from four to six hours, air being excluded, a phenol-like compound is formed, and a volatile amine, ethylmethylamine (the amine boils at 34° to 35°, and its hydrochloride melts at 133°). This reaction is interpreted by Z. H. Skrauk[378] and L. Wiegmann to indicate that the nitrogen is directly connected with two alkyl groups--that is, ethyl and methyl.

[378] _Monatsb._, x. 110-114.

G. N. Vis,[379] after a careful review of the whole of the reactions of morphine, has proposed the following constitutional formula as the one that agrees best with the facts:--

CH--CH--CH--CH--CH----------------C--CH--CH
| | | | | |
CH--CH--CH--O NMe--CH₂--CH(OH)--C--CH--CH

[379] _J. pr. Chemie_ (2), xlvii. 584. Knorr’s formula is--

CHOH--CHO--CH₂
/ | \
OH.C₁₀H₅ | >
\ | /
CH₂---CH.NMeCH₂

_Ber._, xxii. 1113-1119.

§ 355. =Tests for Morphine.=--(1.) One hundredth of a milligrm. of pure morphine gives a blue colour to a paste of ammonium molybdate in sulphuric acid; 20 mgrms. of ammonium molybdate are rubbed with a glass rod in a porcelain dish, and well mixed with 5 drops of pure strong sulphuric acid and the morphine in a solid form applied; titanic acid and tungstates give similar reactions.

(2.) Morphine possesses strong reducing properties; a little solid morphine dissolved in a solution of ferric chloride gives a Prussian blue precipitate when ferridcyanide solution is added. A number of ptomaines and other substances also respond to this test, so that in itself it is not conclusive.

(3.) =Iodic Acid Test.=--The substance supposed to be morphine is converted into a soluble salt by adding to acid reaction a few drops of hydrochloric acid, and then evaporating to dryness. The salt thus obtained is dissolved in as little water as possible--this, as in toxicological researches only small quantities are recovered, will probably be but a few drops. A little of the solution is now mixed with a very small quantity of starch paste, and evaporated to dryness at a gentle heat in a porcelain dish. After cooling, a drop of a solution of 1 part of iodic acid in 15 of water is added to the dry residue; and if even the 1/20000 of a grain of morphine be present, a blue colour will be developed.

Another way of working the iodic acid test is to add the iodic acid solution to the liquid in which morphine is supposed to be dissolved, and then shake the liquid up with a few drops of carbon disulphide. If morphine be present, the carbon disulphide floats to the top distinctly coloured pink. Other substances, however, also set free iodine from iodic acid, and it has, therefore, been proposed to distinguish morphine from these by the after addition of ammonia. If ammonia is added to the solution, which has been shaken up with carbon disulphide, the pink or red colour of the carbon disulphide is deepened, if morphine was present; on the contrary, if morphine was _not_ present, it is either discharged or much weakened.

=Other Reactions.=--There are some very interesting reactions besides the two characteristic tests just mentioned. If a saturated solution of chloride of zinc be added to a little solid morphine, and heated over the water-bath for from fifteen minutes to half-an-hour, the liquid develops a beautiful and persistent green colour. This would be an excellent test for morphine were it not for the fact that the colour is produced with only pure morphine. For example, I was unable to get the reaction from morphine in very well-formed crystals precipitated from ordinary laudanum by ammonia, the least trace of resinous or colouring-matter seriously interfering. By the action of nitric acid on morphine, the liquid becomes orange-red, and an acid product of the formula C₁₀H₉NO₉ is produced, which, when heated in a closed tube with water at 100°, yields trinitrophenol or picric acid. This interesting reaction points very decidedly to the phenolic character of morphine. On adding a drop of sulphuric acid to solid morphine in the cold, the morphine solution becomes of a faint pink; on gently warming and continuing the heat until the acid begins to volatilise, the colour changes through a series of brownish and indefinite hues up to black. On cooling and treating the black spot with water, a green solution is obtained, agreeing in hue with the same green produced by chloride of zinc. Vidali[380] has proposed the following test:--Morphine is dissolved in strong sulphuric acid, and a little arsenate of sodium is added; on gently warming, a passing blue colour develops; on raising the temperature higher, the liquid changes into green, then into blue, and finally again into green. Codeine acts very similarly. The following test originated with Siebold (_American Journal of Pharmacy_, 1873, p. 544):--The supposed morphine is heated gently with a few drops of concentrated sulphuric acid and a little pure potassic perchlorate. If morphine be present the liquid immediately takes a pronounced brown colour--a reaction said to be peculiar to morphine, and to succeed with 1/10 of a mgrm. In order to obtain absolutely pure perchlorate, potassic perchlorate is heated with hydrochloric acid so long as it disengages chlorine; it is then washed with distilled water, dried, and preserved for use. There is also a test known as “Pellagri’s”; it depends on the production of apomorphine. The suspected alkaloid is dissolved in a little strong hydrochloric acid, and then a drop of concentrated sulphuric acid is added, and the mixture heated for a little time from 100° to 120°, until it assumes a purple-black colour. It is now cooled, some hydrochloric acid again added, and the mixture neutralised with sodic carbonate. If morphine be present, on the addition of iodine in hydriodic acid, a cherry-red colour is produced, passing into green. Morphine and codeine are believed alone to give this reaction.

[380] D. Vidali, _Bull. Farmaceut._, Milano, 1881, p. 197; D. E. Dott, _Year Book of Pharmacy_, 1882.

The acetate of morphine, and morphine itself, when added to ferric chloride solution, develop a blue colour. When 1 molecule of morphine is dissolved in alcohol, containing 1 molecule of sodium hydroxide, and 2 vols. of methyl iodide are added, and the mixture gently heated, a violent reaction sets in and the main product is codeine methiodide (C₁₇H₁₈NO₂OCH,MeI). If only half the quantity of methyl iodide is added, then free codeine is in small quantity produced; if ethyl iodide be substituted for methyl, a new base is formed homologous with codeine--codeine is therefore the methyl ether of morphine. If morphine is heated with iodide of methyl and absolute alcohol in a closed tube for half an hour at 100°, methyl iodide of morphine is obtained in colourless, glittering, quadratic crystals, easily soluble in water (C₁₇H₁₉NO₃MeI + H₂O); similarly the ethyl iodide compound can be produced.

If morphine is heated for from two to three hours in a closed tube with dilute hydrochloric acid, water is eliminated--

(C₁₇H₁₉NO₃ = C₁₇H₁₇NO₂ + H₂O),

and the hydrochlorate of apomorphine is produced. This succeeds when even ½ mgrm. is heated with 1/10 c.c. of strong HCl, and the tests for apomorphine applied.

If concentrated sulphuric acid be digested on morphine for twelve to fifteen hours (or heated for half an hour at 100°), on adding to the cooled violet-coloured solution either a crystal of nitrate of potash or of chlorate of potash, or a drop of dilute nitric acid, a beautiful violet-blue colour is produced, which passes gradually into a dark blood-red. 1/100 of a mgrm. will respond distinctly to this test. Fröhde’s reagent strikes with morphine a beautiful violet colour, passing from blue into dirty green, and finally almost vanishing. 1/200 of a mgrm. will respond to the test, but it is not itself conclusive, since papaverine and certain glucosides give an identical reaction.

§ 356. =Symptoms of Opium and Morphine Poisoning.=--The symptoms of opium and morphine poisoning are so much alike, that clinically it is impossible to distinguish them; therefore they may be considered together.

=Action on Animals--Frogs.=--The action of morphine or opium on frogs is peculiar: the animal at first springs restlessly about, and then falls into a condition extremely analogous to that seen in strychnine poisoning, every motion or external irritation producing a tetanic convulsion. This condition is, however, sometimes not observed. The tetanic stage is followed by paralysis of reflex movements and cessation of breathing, the heart continuing to beat.

=Dogs.=--0·2 to 0·5 grm. of morphine meconate, or acetate, injected directly into the circulation of a dog, shows its effects almost immediately. The dog becomes uneasy, and moves its jaws and tongue as if some peculiar taste were experienced; it may bark or utter a whine, and then in a minute or two falls into a profound sleep, which is often so deep that while it lasts--usually several hours--an operation may be performed. In whatever attitude the limbs are placed, they remain. The respiration is rapid and stertorous, and most reflex actions are extinguished. Towards the end of the sleep, any sudden noise may startle the animal, and when he wakes his faculties are evidently confused. A partial paralysis of the hind legs has often been noticed, and then the dog, with his tail and pelvis low, has something the attitude of the hyena. Hence this condition (first, I believe, noticed by Bernard) has been called the “hyenoid” state. If the dose is larger than 2 to 3 grms. (31 to 46 grains), the symptoms are not dissimilar, save that they terminate in death, which is generally preceded by convulsions.[381]

[381] MM. Grasset and Amblard have studied the action of morphine in causing convulsions in the mammalia. They found that if small doses of hydrochlorate of morphine (from 1 to 15 centigrammes) are administered to dogs, the brief sleep which is produced may be accompanied by partial muscular contractions (in one paw, for instance), which are renewed at variable intervals. Then occur true convulsive shocks in the whole body or in the hind limbs. After an interval, the phenomena recur in more intense degree, and are followed by true convulsions. Regularly, ten or sixteen times a minute, at each inspiration, the hind limbs present a series of convulsive movements, which may become general. Sometimes they are excited by external stimulation, but they are usually spontaneous. The sleep may continue profound during this convulsive period, or it may become distinctly lighter. These convulsive phenomena may continue, with intervals, for an hour. Differences are observed with different animals; but the chief characters of the phenomena are as described. In certain animals, and with small doses, there may be a brief convulsive phase at the commencement of the sleep, but it is much less constant than the later period of spasm. These convulsions, the authors believe, have not previously been described, except as a consequence of very large doses, amounting to grammes. The period of cerebral excitement, described by Claude Bernard as occurring at the commencement of the sleep from morphine, is a phenomenon of a different order. The conclusions drawn from the experiments are--(1) That morphia is not diametrically opposed to thebaine, as is often stated, since it has, to a certain degree, the convulsive properties of the latter alkaloid. (2) That the excitomotor action of opium cannot be exclusively attributed to the convulsive alkaloids, but is, in fact, due to those which are soporific. According to the ordinary composition of opium, 5 centigrammes of morphine represent about a milligramme of thebaine. But these experiments show that the quantity of morphine has a much more powerful convulsive action than a milligramme of thebaine. (3) There is not the supposed antagonism between the action of morphine on the frog and on the mammalia. (4) The researches hitherto undertaken on the antagonism between morphine and other agents need to be repeated, and a separate study made of the substances which antagonise the convulsive and soporific action.

=Goats.=--According to Guinard, goats are proof against the narcotic influence of morphine. Large doses kill goats, but death is caused by interference with the respiratory function. A young goat weighing 30 kilos, showed little effect beyond a slightly increased cerebral excitability after two doses of 8 and 8·5 grms. respectively of morphine hydrochlorate had been administered by intravenous injection, the second being given an hour and a half after the first. To the same animal two days afterwards 195 grms. were administered in the same way, yet the goat recovered. The lethal dose for a goat seems to be no less than 1000 times that which will produce narcotism in man, and lies somewhere between 0·25 to 0·30 per kilo. of the body weight.[382]

[382] _Compt. Rend._, t. cxvi. pp. 520-522.

=Cats and the Felidæ.=--According to Guinard,[383] morphine injected subcutaneously or intravenously into cats, in doses varying from 0·4 mgrm. to 90 mgrms. per kilo., never produces sleep or narcotic prostration. On the contrary, it causes a remarkable degree of excitement, increasing in intensity with the dose given. This excitement is evidently accompanied by disorder in the functions of the brain, and if the dose is large convulsions set in, ending in death. According to Milne-Edwards, the same symptoms are produced in lions and tigers.

[383] _Compt. Rend._, t. cxi. pp. 981-983. The _bovine_ animals also get excited, and no narcotic effect is produced by dosing them with morphine.--_Compt. Rend. Soc. de Biologie_, t. iv., v.

=Birds=, especially pigeons, are able to eat almost incredible quantities of opium. A pigeon is said[384] to have consumed 801 grains of opium, mixed with its food, in fourteen days. The explanation of this is that the poison is not absorbed; for subcutaneous injections of salts of morphine act rapidly on all birds hitherto experimented upon.

[384] Hermann’s _Lehrbuch der exper. Toxicologie_, p. 374.

§ 357. =Physiological Action.=--From experiments on animals, the essential action of morphine on the nervous and arterial systems has in some measure been examined. There is no very considerable action on the heart. The beats are first accelerated, then diminished in frequency; but very large doses introduced directly into the circulation at once diminish the pulsations, and no acceleration is noticed. The slowing may go on to heart-paralysis. The slowing is central in its origin, for on the vagi being cut, morphine always quickens. With regard to the peripheric ends of the vagi, small doses excite, large paralyse. If all the nerves going to the heart are divided, there is first a considerable acceleration, and then a slowing and weakening of the pulsations. The arterial blood-pressure, at first increased, is afterwards diminished. This increase of blood-pressure is noticed during the acceleration of the pulse, and also during some portion of the time during which the pulse is slowed. Stockman and D. B. Dott,[385] experimenting on rabbits and frogs, consider that a medium dose of morphine first of all depresses the spinal cord and then excites it, for tetanus follows. If morphine is in sufficient quantity thrown into the circulation then tetanus at once occurs. It would thus appear that depression and stimulation is entirely a matter of dosage. Gescheidlen, in his researches on the frog, found the motor nerves at first excited, and then depressed. When the doses were large, there was scarcely any excitement, but the reverse effect, in the neighbourhood of the place of application. According to other observers, the function of the motor nerves may be annihilated.[386] According to Meihuizen, reflex action, at first much diminished, is later, after several hours, normal, and later still again increased. The intestinal movements are transitorily increased. In the dog there has been noticed a greater flow of saliva than usual, and the flow of bile from the gall-bladder is diminished. The pupils in animals are mostly contracted, but, if convulsions occur towards death, they are dilated.

[385] _Brit. Med. Journ._ (2), 1890, 189-192.

[386] _Arch. f. d. Ges. Physiol._, vii. p. 201.

§ 358. =Physiological Effect of Morphine Derivatives.=--By introducing methyl, or amyl, or ethyl, into the morphine molecule, the narcotic action is diminished, while the tetanic effects are increased. Acetyl, diacetyl, benzoyl, and dibenzoyl morphine, morphine sulphuric ether, and nitrosomorphine are all weaker narcotics than morphine, but, on the other hand, they depress the functions of the spinal cord and bring on, in large doses, tetanus.

The introduction of two methyl groups into morphine, as in metho-codeine, C₁₇H₁₇MeNO(OH)-Me, entirely alters the physiological effect. This compound has an action on voluntary muscle causing gradual paralysis.

The chlorine derivatives, trichlormorphine and chlorcodeine, have the characteristic action of the morphine group on the central nervous system and, in addition, act energetically as muscle poisons, soon destroying the contractile power of the voluntary muscles with which they first come into contact at the place of injection, and more gradually affecting the other muscles of the body.[387]

[387] R. Stockman and Dott, _Brit. Med. Journ._ (2), 1890, 189-192.

§ 359. =Action on Man.=--There are at least three forms of opium poisoning:--(1) _The common form_, as seen in about 99 per cent. of cases; (2) A very _sudden form_, in which death takes place with fearful rapidity (the _foudroyante_ variety of the French);[388] and (3) a very rare entirely _abnormal form_, in which there is no coma, but convulsions.

[388] Tardieu, _Étude Méd. Légale sur l’Empoisonnement._

In the _common form_ there are three stages, viz.:--(1) Excitement; (2) Narcosis; (3) Coma. In from half an hour to an hour[389] the first symptoms commence, the pulse is quickened, the pupils are contracted, the face flushes, and the hands and feet reddened,--in other words, the capillary circulation is active. This stage has some analogy to the action of alcohol; the ideas mostly flow with great rapidity, and instead of a feeling of sleepiness, the reverse is the case. It, however, insensibly, and more or less rapidly, passes into the next stage of heaviness and stupor. There is an irresistible tendency to sleep; the pulse and the respiration become slower; the conjunctivæ are reddened; the face and head often flushed. In some cases there is great irritability of the skin, and an eruption of nettle-rash. If the poison has been taken by the mouth, vomiting may be present. The bowels are usually--in fact almost invariably--constipated. There is also some loss of power over the bladder.

[389] In a remarkable case related by Taylor, a lady took a large dose (supposed to be 1½ oz.) of laudanum, and there were no symptoms for four and a half hours. She died in twenty-two hours.

In the next stage, the narcosis deepens into dangerous coma; the patient can no longer be roused by noises, shaking, or external stimuli; the breathing is loud and stertorous; the face often pale; the body covered with a clammy sweat. The pupils are still contracted, but they may in the last hours of life dilate: and it is generally agreed that, if a corpse is found with the pupils dilated, this circumstance, taken in itself, does not contra-indicate opium or morphine poisoning. Death occasionally terminates by convulsion.

The _sudden form_ is that in which the individual sinks into a deep sleep almost immediately--that is, within five or ten minutes--and dies in a few hours. In these rapid cases the pupils are said to be constantly dilated.

Examples of the _convulsive form_ are to be sought among opium-eaters, or persons under otherwise abnormal conditions.

A man, forty years old, who had taken opiates daily since his twenty-second year--his dose being 6 grms. (92·4 grains) of solid opium--when out hunting, of which sport he was passionately fond, took cold, and, as a remedy, administered to himself three times his accustomed dose. Very shortly there was contraction of the left arm, disturbance of vision, pain in the stomach, faintness, inability to speak, and unconsciousness which lasted half an hour. Intermittent convulsions now set in, and pains in the limbs. There was neither somnolence nor delirium, but great agitation; repeated vomiting and diarrhœa followed. After five hours these symptoms ceased; but he was excessively prostrate.[390] There was complete recovery.

[390] Demontporcellet, _De l’Usage Quotidien de l’Opium_, Paris, 1874.

One may hazard a surmise that, in such a case, tolerance has been established for morphine, but not for other morphine alkaloids in the same degree, and that the marked nervous symptoms were in no small degree the effect of some of the homologous alkaloids, which, in such an enormous dose, would be taken in sufficient quantity to have a physiological action.

There are several instances of a relapsing or remittent form of poisoning--a form in which the patient more or less completely recovers consciousness, and then sinks back into a fatal slumber. One of the best known is the case of the Hon. Mrs Anson (January 1859), who swallowed an ounce and a half of laudanum by mistake. After remaining in a comatose condition for more than nine hours, she revived. The face became natural, the pulse steady. She was able to recognise her daughter, and in a thick voice to give an account of the mistake. But this lasted only ten minutes, when she again became comatose, and died in fourteen hours.[391]

[391] Taylor, _op. cit._