Codeinum

Volume III — Main text

Codeinum, alkaloid obtained from Opium, CigHj^NOj.HjO.

1. Provtngs. — 1. In G. W — , act. 17,2 gr. taken every other m. an h. before breakfast caused slight contraction of pupils, feeling of stiff^ness in integuments over forehead, and occasionally troublesome itching of skin, chiefly affecting forehead and shoulders. Same dose taken towards bedtime sometimes caused slight drowsiness, contraction of pupil from ^ to ^ and acceleration of pulse a few beats. (Harley,

«/., p. 175,)

1. W. W — , iet. 19, took C. in increasing doses. No efl*ects followed until dose reached 4 gr. Half an h. afterwards there was sudden increase in temp, of skin, and, to use his own expression, he '^ broke

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out into a feverish heat." Pulse was slightly accelerated, pupils contracted, and there was considerable giddiness, obliging him to sit down for an h. After continuing 2 h., these symptoms passed oft'. On one occasion he took food at end of 3 h., but within an h. vomited it> and for some h. afterwards was troubled with rumbling and ^^ripin^ pain iti belly. On another occasion thc^e symptoms recuired, but the nausea did not end in vomiting, and it passed off after two loose stools. There was no inclination to sleep on either occasion. (IM.)

1. S. M — , :cr, 49. Pulse 74, pupils at light j), aside j^,

a. Injected subcutaneously 1 gr. of C. 20 m., pulse unchanged; felt a little heavy. l h., puUe 68 ; pupils -j^^, aside ^. Was drowsv. 2 h., pulse 64 \ pupils as before ; somnolency passed off. A little heaviness continued for the following h. There were no after-effcctj,

h. Injected at 7«4.5 p.m. gr. ij. Rc^p, 19; urine acid, sp gr. 10264 * s^'^ sweating. Had taken a chop and tea at 6 p.m. Somnolency came on in \ h. I h , pulse accelerated 15 beats, fuller and stronger -, pupils ^, sideways ^ ; was drowsy, but presented no appearance of heavmos. 2^ h., pulse accelerated ro beats, of same volume and power as before injection ; resp. 18 \ pupils as at first h. ; anterior part of tongue and hard palate a little dry ; had been very drowsy during the last h., and still continued heavy, gapish, and sleepy. The looks betokened heaviness, and the membranes of the eye were slightly injected \ skin moist and cool \ no nausea. Passed, alter a prolonged effort, nearly ^ij of urine, oi sp. gr. I02+, otherwise resembling that passed before the injection. Walked home, still feeling a little drowsy. Slept well ; no after-effects.

c. Injected 2 gr. ; pulse 74, tongue wet and clean. I h., pulse accelerated 8 beats, unchanged ; pupils fY, sideways j^. Somnolency came on after \ h., and continued, but as yet he had not slept. 2 h., acceleration of pulse continued, it was now slightly increased in volume and power. Had slept for \ h. Felt a little squeamish. 3 h., pulse accelerated 4 beats, of same volume and power as before injection ; pupils contracted as before, sclerotic a little injected \ anterior part of tongue dry. The nausea continued for an h., and was accompanied by general warmth and itching of skin, especially between shoulders. Still continued to feel drowsy. The somnolency passed off as he walked home. There were no after-effects. [Ihid^

1. In the dose of o' I grm. C. caused increasing bitter taste, frequent eructation, violent pains in stomach, nausea, incliiution to vumit, salivation, confusion and heat of head, feeling of pressure in forehead and temples, occasional tinnitus aurium, weak sight, inability to engage in mental work ; pulse slow (in one observer it went down 28 beats in the first 4 h.)» small and weak. After 4 h. trembling of whole body, lasting several h. till he went to sleep. Next d. drowsiness, slowness of flow of ideas, diminished attention. In one prover it caused feeling of pleasant warmth, confusion of head, dysurla, and sleepiness.

(SCHROFF, 9p, Ctt.^ 516.)

1. I gave the crystallized nitrate to several of my pupils, taking ic myself also. No one felt anything up to 3 gr., but 4—6 gr. produced somewhat remarkable effects, — at first, acceleration of pulse and heat

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in head and face; then striking mental excitement like that produced by intoxicating drinks, a pleasant feeling and lasting some time. It was accompanied by very pronounced itching, beginning in head and spreading over whole body. After some h. this state was followed by a disagreeable depression, with nausea and occasional vomiting. None of us observed the least tendency to sleep, except after the stage of depression. We did not push the dosage further. (Gregory^ Joum. d€ Pharm.^ xx» 85. 1834.)

11, Poisonings. — !. A man, depressed and languid, had for some time been passing large quantities of urine (sp. gr. 1038), containing a great quantity of oxalate of lime in octahedral crystals and abundance of sugar. One m. he took a pill containing 4 gr. C. and ^ gr. sulphate of strychnia at 9.30. Soon after 10 he felt uncommonly jolly, as if up to anything. Had a genial glow all over him. After walking 2 h. he sat down to write, and could not sec letters distinctly. Suddenly sight failed him and he felt the room going round. He got into the open air, feeling very bewildered. He knew he met two ladies, rccog* nising their voices, but could not speak to them. At 1.30 he was standing indoors with a terrified look, was very pale, and had large beads of sweat on his forehead. Pupils slightly contracted, radial pulse scarcely perceptible, surface of body cold and clammy,and voice reduced to a whisper. Had vomited a mouthful. Said he felt ^^ sick as death." A tumbler of hot water containing brandy and ammonia was immediately ejected. Lay down, and was wrapped in warm rugs. In A h. began to improve, was not sleepy, only terribly sick, as after smoking a lot of bad tobacco. He remained thus till 10 p.m. On slightest movement, began to retch violently. No sleep all n., slightly delirious. Got up at 9 a.m., very sick and ill. Pulse 56, surface cool, face pale, pupils much contracted. Had passed about 6 oz. urine^ sp. gr. 1018, no sugar, oxalates plentiful. No appetite all d. After tea and toast in e. he went to bed, slept well and felt himself in m. (A. S. Myrtle, M.D., Brit. Med. Journ., 1874, i, 478.)*

HI. Experiments on animals, — I. a, HaRLEV injected gr. 1*07 beneath skin of a bitch that was very susceptible to action of morphia. Eyelids became swollen in 20 m., and continued so for 25 m. more. Pulse fell in \ h. from 120 to 80, and thence to 64, always accelerated by inspiration. She remained very quiet and timid, as if feeling poorly, till gth h., when she had returned to her usual condition. Till then no excretion had been passed. For Rrst 3 h. there was nausea, and during part of this time a little tendency to sleep, but she did not close her eyes throughout. Pupils were unaffected ; secretions of mouth increased. Later, she received 2 gr., without any other effect. He then injected 3 gr. into a stout beagle weighing about 40 lb. ; and, there l>cing no change in 4 h., 3 gr. more. Within a few m, followed whining and restlessness, and repeated action of bowels. After 2 h. resp. was irregular, wholly abdominal, ^'expiration consisting in a prolonged collapse of abdominal muscles, accompanied by a subdued whine

• Wc have given this case in iptte of i(s lack of purity, a« the dose of strychflfl was toM stx\A\ to produce physiological effects, and in fact none of its characterubC fymptoms ap}>ear in those rccordrd. — Eds.

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ending with a slight grunt/' Heart's action weak and irregular ; pulse 65, respiratory. Pupils contracted closely at light. After 3J h. rcsp. was 8 only, but now thorax moved slightly; pulse 84, very feeble, ranging 60 — 120 during each inspiration. Dog lay down most of time^ but walked well though feebly. After 6th h. gradual recovery ensued, but he continued for some time in a restless whining state, not lying more than 2 — 3 m. in same place. As he lay down his flaccid legs were slightly jerked with faint spasms; ac and h. muscles of chest occasionally quivered with a much stronger spasm.

b, Jn the mouse C. produced the same effect as morphia (11, 6) ; but the forward movements were after a time performed by a series of little jerks, and then tetanic convulsions came on, in which respiration (previously shallow and irregular) became arrested, and death ensued. P,m.yl. heart was empty, pale, and contracted ; r.distended. (Op, clt.y p. 170.)

The oiher alkaloids of Opium mu$t be more briefly prcKnted,

Cryptopla. — This has nrcehred little examination save from Harley («/. cit., pp. t $6 — 16S), who has experimented on man, on the ilog, and on the mouw. His conclusions arc as follows :— i. Crypiopia, like morphia, has two distinct effects, an hypnotic, and an excitant of a most remarkable and exceptional kind, dependent partly upon an illusion of vision, and partly upon a tendency to convulsive action, f This is in animals ; H — says : " I have as yet been unable, after careful inquiries, to detect the slightest tendency to illusory- or other excitant effects in man,") a. The hypnotic effect is both considerable and protracted in those who are readily calmed by morphia. No unnfeatant effects have followed it* use (in man). 3. Its action upon the respiratory function is first stimulant, but subsequently depressant, and death is the direct consequence of this depressive effect. 4. The effect on the heart'saction is rcgidatcd by that on the breathing, and is therefore indirect. 5. In large doses C. caiues dilatation of pupils.

ISeconinnm. — This, too, is chiefly known — pathogenetically — through Harley (pp. 151 — »s^)- Atlminintcrcd by the stomach, it has no ertcct, or so slight n one as to be inappreciable. By the »kin,gr. ^ to 3 is iranqutllising and hypnotic.and is not foDowcfl by any unplcaitant results. In animals similar effects were nhserved; hut when gr. } proved fatal to a vigorous mouse (p. 347), there were convuUion<^ before death, and Tor 10 m. after. The kidneys were congested, the bladder distended, and the urine (as did that parsed % h. after the dose) contained many blood-corpuscles.

Ifaroelnum has been declared by Bernard, Behier, Debout, Lin£,and Eulenburg to potsess narcotic power tecondary only to that of morphia. Da C'oHta and Harley find it much less active, and ascribe its efficacy in the hands of the French observer* to admixture with codeia or mcconine. Such as It is, ir seems purely hypnotic, and it) action leaves no disagreeable alier-effrcts. Anuria and dy<>uria have been noted from it> use; but Harley cou&idcn these mechanical effects, its insolubility leading to its precipitation in the urinary passages. In animals, given in sufficient dose, it kills by paralysing the respiration, without producing convulsion. (HaRLEY, op. ctL)

ITarcotinum. appears to be, in the lower animaU, a convulsant. Schroff^ and Tully have proved it on the human subject. The former found in the dose of 7 to 15 centigr. at first increased quickness of pulse by 6 — 11 beats, then as many bcatu under normal. The temperature first rose o'i° C, then sank 018*^ C. Taste insipid, not bitter; sometimes scrapy feeling. Soon alter taking it a transient headache with humming in head, redness of lace, injection ot eye-, dilatiition oi pupils. Increased transpiration, peculiar disagreeable f'ormiration in limbs, agreeable warmth in chest, deeper breathing, pleasant disposition, weakness and drowsiness, followed by coldness and rigor, especially in back. The muriate in doses of a decigr. caused

<n-g\isting, bitter, astringent and acrid ta-itc. After i h. rigor all over body, slight pressure in forehead, heat and redness of face. {Lehrh. d. PAarm.)

Pruf. Tuily proved N. on eight persons. In the fin.t, i gr. at lo a.m. reduced puUc hoii) TO to 60 in 4 ^* Four gr. more, taken at 4, brought it down by 5 to 52, and it was softer and murL- compressible. By 5.30 there was also mazy and confused fetl id" head; by 6 considerable languor, perspiration, and vertigo increased on motion ; by 7 much somnolency, disagreeable sensation in epigastrium, itching of surface, and hoarseness; by 7.30, slight thickness of speech and vacillation of gait, and hhuitUT emptied itstif slowly and with difficulty. All these symptoms increa*i«d for 1 li. more, and then remained with '^me variations up to 11, when he vvrnt to bed, slept heavily, and woke m m. with mouth somewhat dry and clammy, and still some diHicuky in evacuating bladder. The second took same doses, and had same symptoms, with also nausea and repeated vomiting. The third was as the second, but his symptoms lasted all next d. ; both found that a short walk improved all symptomt for the time. A fourth took 8 gr. at ii a.m. About 11.30 began to feel highly plt-asuntbltr sensations; hy ti itching of whole surface, most intense at nose and inside thighs, increasing up to z.30, after which it gradually subsided. From 12.30 much somnolency, increasing up to 5, Pulse went down (from 68} 10 48 ; pupils were contracted. Other symptoms as in former provers. Next three experiments were with small repeated doses, — gr. \ every « or 3 h. in two, gr. j every b. in a third. Same symptoms were produced. {Bojt. Mtd. and Surg. Joum., vii, 37.)

All this is in strange contrariety with H. C. Wood's statement that " xo or jo gr. have frequently been taken without effect, and even doses of lao gr. are said to have been exhibited with no greater results.'* (Narcotine is not mentioned by Harley.)

Papaverinum has been experimented with by Hormann {Wien. med. Ifochauckr. for 186S), who took on 3 successive d. doses of gr. 1 — 8 of the muriate. In i\ b. after 3rd dose, severe hiccough came on, and lasted for 6 m., followed by pain in epigastrium, and when this disappeared frontal headache came on. (Sec Allen** EncychpaJiaf sub voce.)

Thebainiun acts on animals like strychnia. Two gr. injected by Harley under the skin of a dog weighing 15 lb. killed it in i h. by arrest of the respiratory movements. " Kabuteau took 10 centigrs., with the production only of a feeling of

tightness in the head " (W^ood).