Lectures on Pharmacology for Practitioners and Students |
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LECTURE o COLOG p :FOR BY ~z T T. oaD. ,aor 0& A. J) Gill tv. .." I1TIlT PIlAaM COL IC~L T LATED FRO 1 THE E 0 D GER. BY EDITIO RTH '. L TH .B.O ..OA TAB., I.. DCLl rJ' TR ,. LLI, 0 LLO 1. Til 1l,'1\ & ITt 01' \) 1'01D. I. TH 1 5. H lET TR L TO PREF E. f ho h The Lo DO..' 01: mb Y, I 95. cond erman i ion 0 1'0- new ern ion. n dd , nd 1'0£ or inz, b proof hee . IV h vie and m ke lit ral o doin he h not AUTHOR' PREF CE /p1) ECO C EDITIO 0,,4+the fol1owin page I have endeavonred to pre ent, IV :.~:r a po ihle in a practical form, .. complete accoont of our pharmacologic 1 kno led e. The chapter do not corre pond altogether with he individual lectures, but with thi c ption, he book i 0 all intents and purpo e a repro-duction, in bo h forID an ub ance, of a cour e of lecture and d monstr tion hich ex end over two erne tel' . t i not int nded th t thi hould b a text-book of pecial Therapeutic, though referenc ha been made to variou di ea e and b ir l' atment. Oa e w re elected for hi purpo e which pre ented man of be condi ion of cientific xperiment; uch ca e 801' often much mol' in ruc ive than a number of xperiment on animal. I h e avoi~ d t icological detail, heth r they refer o n I -di co r d poi on ,or 0 he eft ct of well.known poi on , or drug , on par icular organ ,unle the d tails ha om p cial ignific nc or he m ical id of ph 1'- macolo I have 1 0 avoide ny di cu ion on fac or h orie hich ere not likel 0 be intere ting to the m jori y of m uden or r dr. he quo ions from the ~ ri in of 0 her re, with fev c pion , tak n from h ori inal work ; by mean of them vi UTHOR' PREF E. refer nce can readily b made to any other important tr ati e upon the ubjec. On of my critic has remarked that these lectures show h t pharmacology i more intere tin than many phy icians and u ent im' gin. I hope hi may till be aid of the new dition, I hou h in man place he text has been conid rabl bri rr d. ew edi ion u ually tend to be larger han ormer one ; but I h hought i de irable to take an oppo it cur. e nd hay conden ed rather than amplified my materi 1. uffici nt new mat er ha, however, been ad e 0 ju tify h claim ha, in thi edition, the work h b en bo h impro d and nlarged. h en r I principle ~ hich have guided me in reating he ubj of pharmacolo ill be found In th conclud-in chap r of th, e on olume. C. BI Z. CD P. CO T T o OLe 1. P GE LO E TIll OIL b 6 20 47 7499 136 1 0 164 195 228 261 275 299 316 349 OLOG 1. The ope ofPhal'ma ology-Dio oride theftr t to rite a treat' on 't- )l, 'ng of h nn kon-Phal'ma y-Pharmacog11.0 y-D~tferent languag 1 ed-Phar/l acodynam 'c TJ e Pharma op iM- harmacology the 'Ino t a1 cient ort 'on of the h al'ng art, nd the one mo t freque'ntly mploy d-The '111,0 t'recent '11, it c' nt( pplication, i libri qninqu, f om- hn: L ipzi ,I 29-30, 1 (H In H•.r OL po hec r in on hi cont in 1 bu in 3 H R OLOG. no PH R ACOLOG • 5 ician doe ll. ET R. In I 47 the Europe n ... orl wa m rke manner b report from continuou c ul hich n 7 ER. i riol to a r CTIO O.E ETH R 0 contI' ction m h cor-m n (( The D RTO DI 0 ER • E E T' 0 THE UL R TE D TE P A'ru E. 11 ry 0 long .161. 1 75 1 EPE TED ETHERIZ TIO • P D TIO OF LO AL TH I. 13 to rue ion of m he e tination in the eeonom , it i el r from in he n une F 'TH R ttY. TI ondi ion £ he E }.ECT L. LL • I!: • 1"' o 'f b. f. r. TH R TD IT POUR. her, 0 void pot here important pIe, in he I'm, where dir ct irl'ita-h r 11 in e eral c produced ACE'L'I ETHER. 17 bo h of hich are developed in e her b keeping i . f e h I' i pour d upon filtering p pel and then no N d to v pora e, no odour houl r m in ( b ence of deriva ive of fu eloil). f 5 C.c. of eth I' re vapori ed, the re ul ing moist apour mu not redden blue litmu -p per (ab ence of ulphuri, ulphurou nd acetic cid). £ e her i poured o er c u tic po h no ello int mu t b apparen ithin h If an hour ( b ence of ldeh de nd vin 1 alcohol). f h r i r p atedl haken ith olu ion o£ pot ium iodi nd e po ed a unligh £01' an hour, no llow haul b no ice ble (pero ide of h dro n). ther pre r d in th dark in a cool place in bro nI bo Ie filled a the top, for Ii h nd ir d com- 2 ETHER. In he retor . .0 oh. nd I • 1.-0 11·-7 t . 0 penm n. ,. r e ,moun 0 r in pir d III 1 nllnu e. 640 c.cm. 290 C.cm. ... . m. i - . m. ITROU ETHER. 19 Ii!. III. HE I L PROP TIE OF OHLORO OR • 21 ble number of liquids of an etherial nature withou ob a.inin any good re ult , until t 180 t he tried chloroform, a mall quanti of hich h d been given to him by Thoma raham, he di tin ui hed chemi .1 Chloro orm i a limpid colourle liquid of n greeable h ri 1odour and w et ta e. Di, olve in about 110 P rt of er, nd in all propor ion in alcohol, ether and fatty oil. oilin point 600 to 610 C. (1400- 141 • 0 .). pecific 1.502 (1·497-Ph. .). It wa di covered in 1 31 by Li bi t ie en, a a product of the decompo i ion of chlor 1 by cau tic pot h j nd imultaneou 1 by oub iran Pari re u]t of the di illation of a olu ion of chlori-nat d lim nd Icoho1. In 1 34 oma determin d th com-o i ion f chloroform, nd it i nam. r rded i richlorid £ form 1 ( )-£1' m formic acid- 1 W hich i no Ion er p d, hon h h rm i ill u d. I i c lIed trichlor--m tZ ne bec u e i c n be d rived h or m h n C ne molecnle of hi . h 1 cnl of chlorine ive h drochloric cid nd chlo- +3 ] =3 Is· ction of c u ic po a h, o pot h ccording to o HLORO R • o THE TE PER TURE. chloro-ho n b ening of E E TORE PIa TIO • h r no IODO'er 25 L L1 E E F HL RO "0 LOC LI ED EFFECT 0 CHLORO OR • 27 or an endency th reto, he DO PROD OED? HO I ROO I PR DUG D. 29 r d corpu cl s to be acted upon, and place hem bell- 1a which contain a piece of ponge moi tfew minu e he cr tur are mall an amount of chloroform t n, he e open ouch. . of p D? n on per onal u - DETEOTIO OF OHLOROFOR I THE n DILY FL ID • 31 ni r of ilver. Thi b ioed from the 'pir air, ED OR LtEPE TED I H L TIO i quiekl eeompo ed rhonie nd h dl'oehloric 1+ -light deeompo e ufioe ing 1. •.: (c rbon 1 mm ion of Tl!J T OR THE PURIT OF ffLOR FOR • 33 III pr ma here, how- 3 R • ETHYL OHLORIDE. 35 o chloroform by o qu 1 r . m ch n hr.' I 0.14· TH ·L BI IDE. hoI ETHYL BROMIDE. 37 3 I 11 ITRO o 'IDE G 39 I nitre hi h i water: compo ition, nd in 1799 found ou it in oxi-perim nting upon him elf, i rou oxide odour and e ti h ta t ,i h vier han (1'527), and i. mol' olubl in t I' th n 20. On method of pre-m rIC oxide ga b m an of zinc • 2 mmoDlum 170° .,' nd ,Tid O'a and zO. TIlUm III i p 1 "'H LI ITR U IDE EXPERI E IT 41 car ful analy i of the ymptom accompanying hi narco i how that it run the am our e a j th ca e under chloroform or ther. Th cOl,tic 1 ub t nc of th bI' in i h fir t part of he nervou em to b affected, nd it i affect d more tronal than the other part . e t foll w the pinal cord, the m dulla oblongata, and th n the he r. The cornea appear to b unaffec d for orne time, a ,hen touch d i r pond -by he clo ing of th yelid- v n aft I' con ciou ne and the po I' to ill have vani h d. itl! he di ppearance of the n rco i th organ l' cov l' heir functional activity in the rver e or r. ngli h committee, appoint d for the pm'po e of 1'minina h l' Ia ive ime occupied by the ariou t lD h proce , examin d 13 0 ca e. The folIo in ar 1'a at bich he arriv rom 63 0 cond 1'e r uir d to produc anre-he i ; he n Ia t d from 22 to 2 cond; 100 120 econd 1 p from he commenc m nt f he iu-h } tion 0 compI l' co r. In hil ren n 1'CO i, occurred oon l' han in dult. omp} n h ia i c nd of comm nCln a b Ii d h h Thi ca.n be hown by simple about IS centime re o and the other merc~ria.l rough. I n U E F ITR o~ IDE I:r DE T L PER TIO 4 ure iii. . I,. n of inhalin n h two it i furth r uffoc' ion-wi hou a t I' th hiI'd during th proc [PI. o~ IDE I ID IFER . ODE OF ITROU 0 IDE oxid av rent Z E. to of b com of I . Op'llm-It O1'igin-Oon''ltituent - hief alkaloid - o'rphine - areoti .De t-Poi,'onous aeti01 -E.ifl t on the .pinal cord, heart, & ,-It po 1'. of l ening the p ri taltie movem nt of the inte tine- a'reot 'ne, Thebain, and od ine- ubcutan OIl inJ etion of morphine-It advantage and d' ad antage -E retion of 011J!t 'Il -How to r c gni 't and to detennine 't pur'ty- conic a id, a m. an of d te1'mining the re ence of opium and 't . tract -Opi an moking- 'ub t 'tut for opium- onnabi' Indica -Ha, Tti ch-Lactucar'um" Y ET EGET BLE LK LOT 4 animal 0 ni m he remain to con id rable e t nt unchan d, 0 hat hey can be de ect d fter ard in h urin . kalie gener lly precipita hem from th ir aIt : hu if I c; dd cau ic od 0 olu ion of cinchonine h ·drochlor t , the cinchonine i precipitated in floccul n me. The lk loid. ar pI' cipita ed b numb l' of l' , tho e mo employ d being pho pho-mol b i acid, pot. io-mercuric iodid , and iodine in a olution of po a - lum iodid. rIh la r reagent cau e a thick, 1'0\ n depo i hi b i in oluble h n added to a drop of ulphuric cid. ach alkaloid ha i own p cial l' ctions by which i c n be id ntme ; wi home of the e w hall h 0 d aI, an fur b r refer nee will b made 0 hem. n lkaloid con i t of c rbon, hydrogen nd nitroO' n. 10 f h m con in 0 g n 0, but hi i not n n-i I ch l' RPH E. proce in plant re excretory product . ue cha.n in the pI nt, re re not turned to any further pon e; limb ; with COn inuou he ill open hi eye. EFFE T F PHI 51 occur he • TH RT. F THE I E Tl E • 3 re t, note the qu ntity of air expired In thirty cond , and obtain th following results: 230-200-220-200-210-200-210 c.c. lmo t immediately after the injection of ·01 gramme (. I r in) of morphine hydrochlorate into the jugular vein e ob erve a lower mo ion of the index, nd read off- 90-100- 0~C>-90-9C>-90c.c. con iderabl reduc d by ea ily be inexperiment he ai F RP LIE •• TEE ETI • ID n 0 th in e in took pI ee? re no IonO'er in conne ion he t nth dafter ection of the ,mol'phin h eked the mo emen THEB E. 55 from cutadi - of on of d T E LOID F PI PREP R TlO ' PlU • 57 a reddi holution in im m r m rphine DE rn. ip c cuanh and i ht h ving o long a we 1'e me ine modifie PTO BY ODEI :TE. 59 he me t,ime poisonou re uIt have been produced b 00 I rge a do e. child of two year old had 0·1 gramme (1·5 grains) given to it in the cour e of a few hour. The following symptoms are aid to have been produced :-a death-like pallor, coldne of the limb, the pul e and heart-beat imperceptible, the abdomen di tended, the e e fixed and taring with widel dilated pupil , and dr ne of the mucou membrane . timulant w re dmini ered, and after a few hour the child rallied.1 The do e of pho phate of codeine i about three time ha of hydrochlorate of morphine. From 3 to 6 cg. (t to of a rain) ma be administered two or thr e tim a day wi h dvantag. The erman Pharmacopreia ha fi ed ramme ("5 rain) he ma imum ingl do ,and o· ramme (6 r in ) he m imum quan i y 0 b given ·n , n -f Dr hour . H"1 DEI I \D... II I T TIO.. l' ~rORPHINE. HYFODER II 1 DMI I'TRATIO OF ORPHI TE. 61 I J BOUT EOU JEOTIO OF OR HI E. 63 IT. i dr whack. morphine, and THE RPHI E H BIT. 65 2 ) In u r 1- TE • OPIU 67 ervou Di e e at Halle, did not even di ork. 1 at ry e r ct of opium i largely n ed bein inhaled into the lun n denie th t ny of he crib d ri ing fr m hi r c-ium mokin ha b n ron I of nervon di or er .6 comou ht 0 uli r o ill DIOA. 69 mm or mor n of opium give th ame di tinctl a i he ca e ith the Wini r 10 ion 0 he bo BY HA OHI H. EFFEOT PRODUOED BY R ORr OR. :u6. 71 7 I "DI HE IP. n hi orrowing comi ord r. It ha harmacop i , and in ract nd the tincture I DIAN BE P. 73 of liquor from ha chisch is prohibited throughout Egypt. The door of those coffee-houses or inn where it is supplied ill be walled np, and their proprietors imprisoned for three months. All articles containing haschisch will be confi cated and publicly burnt."l And yet, even at the pre ent day, he habitual indulgence in hemp is the cause of many in-curable mental disorders in Egypt, Turkey and A la. It i one of the cau es that ha de troyed the old warlike n rgy of Ea",tern nation . o long a we are unable to obtain stable and active r paration of Indian hemp it has merely a scientific in ere. t.lI The ame may be aid a] 0 of LACTUCABIUM, the dried milky juice of La tuca virosa, the trong-scented Ie uce ( at. Ord. Compo it00) , which wa at one ime fficinal. The following group of hypno iCB r cently rought into u e ha upplied he ant that formerly i t d, and in my opinion enable u to di pen e with uch uncertain preparation tho e of annabi indica or L c uca viro a. I From artin s 'Ph8ormakol. med. S udium iiber den auf., 1 6 . 4. n thi h ad compar th 180 t publication on he ubj c by of P ri in th • Deut ch. m d. ochen chr., 1890 . 679 fl'. HL R L H DR TE. 75 place may sub- . ~. 7 of he drug will have com- TIO OF CHLOR L. 77 he former case from 5 to 10 grammes (75 to in the other from 1 to 3 gramme (15 to 45 more and more profound, the 4 ion of he h ar , rin 0 hich i D E "'D ODE F o HL L. 79 80 TE T FOR THE PURITY OF OHLOR L. into olution of one part in ten of lcohol, hould only be tin ed r d on dryin , and after acidifying the above olution with nitric cid, i hould not, on the addition of nitrate of ilver, imm diately becom cloudy, owina to the formation of chloride of ilver. The e two te ts are to determine the pI' nce or ab nc of an e ces of hydrochloric acid. I pply these test here, you ee that there is a slight I' d nin of the litmu paper at fir ,whilst with the other t t a Ii ht opale cence appears in the te t-tube; some h rochloric acid m y exi t even in the be t preparation, or it may be developed on e po ure to the air, and especiaU to baht. h n hated on the platinum-foil chloral h drate should vol ilize, and hould d v lop no inflammable v pour. rate of chloral, po e ing a neutral or even an alkaline reaction from admi "ture wi h oda, ha been introduced into commer e. On heating uch a pecimen there i a whit I' idue which on bein tested prove to be odium chlorid and oda. If any inflammable vapour i dev loped it ari from the pI' nce of chloral alcohol (C2C130H + RaO), the local effect of which on the tomach i tronger tha that of chloral h dr e, and therefore detrimen al. HLORALU FOR In T hlora1 formamide, i a pre- Ion hich ha r c ntl becom officinal. It con i ts hit brilli n, odour! cr t 1 of a Ii h I bitter 'V hich melt at I 14- t I IS°, and ar lowly solubl In o P I' of I' or in I'5 P rt of alcohol. Its ment a a opormc wa propo d b v. ering in 00 . Th form ion of chior 1 h dra e i indic ted by he pp r nce of uro- bIoI' lic acid in he urine, and he orm ion of ammonium formi te accord ith chemical PAR LDEHYDE. 81 facts. It has been further assumed that leep, which i r nquil and not too profound, is produced by the gradual eparation of the chloral hydrate, and that owing to the formation of a compound of ammonium-a I hall point out to you when I corne to discu s the compounds of ammonium-a gentle stimulation of the ympathetic and re-piratory nervous centres simultaneou ly takes place. Th con equence of the latter is that in animal , during th leep thu produced, the blood-pre sure and the re piration are lowered much Ie than when hydrate of chloral alone i employed. Thi property D'ive chloral formamide a pecial advantage as a soporific where disease of the vascular sv tern exi t . nd it po sesse a furthel' advantage: chloral formamide i not caustic like chloral hydrate, and i therefore better tolerated by individuals with sensitive tomach. From I to 3 grammes (15 to 45 gl'ain ) produce a leep that generally pa es off without any after effect. : 4 grammes (a drachm) i given in the German Pharmacopreia a the maximum dose. It may be admini tered either di solved in water or a a powder.l P RALDEHYDE was recommended a a soporific in I 3 by V. Cervello, of Palermo.2 It is a clear colourle fluid, ha a neutral or very lightly acid reaction, a peculiar ethereal bnt not penetrating odour, and a pungent refr hing ta te; it pecific ravity i 0'99, it boiling-point 123° to 125°. ith 9 par of water it form a. olution which i rendered tnrbid by heat. It mixe in all proportions with alcohol and ther. It i obtained b treating ordinal' aId hyde, H3. 0, at a medium temper ture with a tronD' mineral acid· he aldeh de i thereby c nverted in 0 a polymeride, that i hI' e molecule cond n into one to form ( ;2H4,0h. In warm-blooded animal paraldehyde, like morphine, act fir t upon th cerebrum, thpn on the re piratory centee and h pin I cord. Large do e of it paraly e he re piratory c n r ,and a are ult put a top to re pira ion and the ac ion of 1 Fl'om the numerou paper upon chloral formamide I would el t: E. Kny, 'Tb rap. onatshefte,' I 9 . 345' . Lang aard ibid. . 461; . erin u. Zuntz, ibid., .565' E. R icbmann 'D utscb med. cb n chI'. ' 1 9, 0.31 (from Rie el' Klinik). 2 • Oer 110, rchiv f. expCl·iment. Pa.th. und Pharmak. 1882, B . vi, s. 265. 6 PAR LDEHYDE. I , ould r £ r th r ader . 40; . v. oord n. the h ar. The heart' action can be re tor d by artificial repira ion; i i ther fore not dir ctly affected by paraldehyd . do e of fr ill I to 4 erramme (IS grain to a drachm) pI' duc tranquil 1 p in man without cau iner pI' vious excit m u or cer bral conere tion. The patient u uallyawakes cl ar-h ad d an without di aerreeable after-effect.. It doe not produc con ipation, a i he cn, e with morphin, nor d pre ion of the heart' action like chlor 1 hydrate. On th other han, paraldeh de h the following di advan a :-1 irrit lie the mucou membrane of the laryn and of the tomach, if from any cau e the e are already aff ct d. Th y tem peedil become accu tomed to it, 0 ha the do e mu t be increa d. It price i rather high. Th odour of he breath for at lea t twenty-four hour after takinO' h medicine i unpl a ant.l If tb admini tra ion of larg do e of paraldehyde i con-inu d f01' an 1 n h of time the brain become affected. Th ymptom approximate very cIa e1 to tho e produced by alcohol; remor, 10~ of memory and rea OD, delirium, hallucination ,an pilepti£orm attack 801' mentioned. E. Frohner!! ha , mol' over, ob erved other poi onou effects on hoI' n dog, viz. he forma ion of methremog10bin in the bloo he d eneration nd de truc ion of th red corpuscle> h a aO'e of h m tin into the urille, with diminution of 11 moun f th lement in he b100d-re uIt which r imil r to ho hich P rog 1101, ni ro-benzol , pota-ium hlori nd 11i d ub nc are known to produce. Th r ducin c ion of p l' ldeh d -tha i, it power of r adil combininO' i boO' n-i he cau e of i injuriou if u h bl urn n lood, ho vel', i not 0 in hi a that of th animal above men-ion d· 0 uch h e b n b er d in m n nd, wi h ed h rdl r b £ ared £1' m h u u 1 do Th b form in an olution A lYLE E HYDRATE. 83 ou ht not to be given in a concentrated form, as it then cau e a en ation of burning in the mouth, and al 0 affects the tomach. The arne rea on render it un uitable for ubcutaneou injection. ccording to the German Phar-macopooia 5 C.c. (85 drop) is the maximum ingle do e and 10 C.C. (170 drops) the maximum quantity to be given in twent -four hours. YLE E HYDRATE 1S the name of another oporific belonging to the methane serie. It ha the empirical formula C5H1ZO, and from its chemical behaviour appears to be dimethyl-ethyl-carbinol j that is to say, methane (CH4) in which two atoms of H are each replaced by CHg, one atom of H by CZH5, and the fourth by OH j therefore it rational formula is (CHg)z.C.CzHs.OH. Its character, according to the German Pbarmacopooia,are as follow :-a clear, colourless, volatile fluid with a neutral reaction, a peculiar ethereal aromatic odour and cau tic ta te, oluble in 8 part of water, forming a clear mixture with alcohol, ether, chloroform, glycerine, and fat y oil, boiling at 90 to 103°C. (194° to 21T4° F.), and having a pecific gravit of 0'815 to O' 26. It effect i purel soporific, without cau ing appreciable change in the re pir tion or circulation, and without di turbin the int tinal activity or the general condition. The medium do e for a strong adult i 2 gramme (30 gr in). It cannot b nb titut d for morphine in the leeple ne that i cau ed by pain, nor i it 0 ea ily tolerated in irritable condition of the tomach a i the la tel'. n thi account amyl ne h drate i always giv n with a large amount of liquid, no Ie than 50 C.c. ( bout 4 table poonIul). Extract of liquoric erv to cover it ta te j it is readily taken in 1 in c pule j 4 c.c. (a drachm) is the maximum ingle do e. It rna al 0 be admini tered a n enema (5 i h 50 of at l' and 20 of mucilage). On accoun of i irri a ing prop l' ie when appli d locally, it i not a uitable prep ration for ubcutaneou inj etion. In mo l' te do e am 1 ne h drute chi fl aff ct he c rebrum j in 1 rger do e it ff ct h pinal cord a well. fle cit bili i 10 , he re 'piration become le fre-quen and la t cea ,complet paral of the heart m anwhile bing gradually de eloped. ULPHO AL. my1 ne h'dr te wa introduced into medical practice in 7.1 inc that time it qualities have been much dis-n , and in all e ential points the original estimate of h m ha been confirmed. Th employment of ULPHO L a a ubstitute for morphia i of more rec nt da e: it n e wa sugge ted by . Ka t,2 i mode of production by chemical proce e having been pr ViOll ly di covered by E. Baumann. The German Pharmacoprei thu de cribe it:-colourle ,odourles, and ta tele s pri matic cr tal, which are entirely di ipated by heat; one par of it form neutr 1 olution with 500 parts of cold and 15 part of boiling wattlr, with 65 of cold and 2 part of boiling alcohol, al 0 rvith 135 parts of ether. It melt at 1250 to J26° O. ulphonal, (02H5 °)...0.( HS)2' is an oxidation product r uiting from he combination of ethyl mercaptan with ac t ne, and con equently may be regarded as methane (OH4) in which two atom of H are replaced by two molecules of di-e h I. ulphonic acid, and the two other atom of H b two mol cule of methyl. The empirical formula i 7 16 20. It i l' garded much in the ame light as tIl lene h dr te, but a a rule leep is not induced until e 1'801 hour after i e hihition. It Ie er olubility in h in e tin 1 canal i probably the explanation of thi , hich i di inct drs. hack to it u e. leep ha ome-im not foll ~ e he do e for ten hour ; when it did t ke pI c i ch rac er w perf ctl n tural. The variabl ff c hi h iv u do e produc s upon th ame individual m be ociat d wi h thi unc rtainty with l' gard to it b rp ion· n ime 5 gr mme (75 grain) may be in ff ctu 1, anoth round Ie p m rtl ult from ·5 r mm (TS r in ). ulphonal do not pro uc the di O'ree hI after-effect which folIo he mini r tion of morphin ; on he 0 her h n ,in be 1 pI n cau ed b p in it i powerle to pI' uc b 0 hin ff ct on he br in , hich i induced morphine. nlike chI l' 1, ulphonc 1 ha n irrita ing ct on h u, nor 0 i e en in large do e affect rin , Th rap u i h ona h fte, 18 7 8.249. t, ' .B rlin. lin. ochenschr/ 18 , . 309. TRIO L. 85 he circulator sy t m. A transitory cutaneou ruption ometim follow it u e.1 om time after its administration, e pecially in women, b matoporphyrin, a derivative of hremoglobin which contains no iron, appear in considerable quanti tiE', in the urine, and give it a dark red tinge.2 ephriti may 0.1 0 follow the longo-continued u e of this remedy. It i be t admini tered as a powder, in do e for adult of I to 3 goramme (15 to 45 grain). The German Pharmacopooia fixe the maximum do e at 2 grammes. TRIO AL i. the name of a new preparation which may be reg-arded a ulphooal modified by the ub titution of a molecule of ethyl for one of the molecule of methyl in the compo ition of the latter. It occurs in colourless, glittering tabular cry t 1 , wbich have a omewhat bitter ta teo It di - olve in 320 part of cold water, and more readil in warm water. It i ea il oluble in alcohol and ether. leep is induced more quickly aft l' tl'ional than after sulphonal, and unplea ant after-effect are so rarely produced that at pre ent it i regarded as the b t hypnotic. Hrematoporph rin, however, appe rs 'ometime in the urine after its admini tration. an hypnotic it may be given a a powder in ingl do e of I to 2 gramme. (IS to 30 grain ), bu t like other narcotic it i injuriou if taken 00 frequen ly. T TRO L i a ulphonal which contain four molecule of eth 1, and act in a imilar fa hion. It i , however, Ie oluble th n trional, and h a more uoplea ant ta e. Its u e, therefore, rna be dispen ed wi h. 1 G. rkel, I lincb. m d. Wochen cbr.,' 1889 o. 26. 2 koi I ederl. Tyd chr. von Gen e k 18 9, ii, 413. Ranking nd Tardin ton I Lane t I 90, ii p. 607. lk w ky, I Z it chr. f. physiol. Ch mie' I 91, Bd. xv . 286. Garrod, I J urn. of P tboI. and Bac r., I 93, vol. i, pI. ii. In thi paper it i d nied thnt sulphonal i erie to tb pl'esen of brematoporphyrin in th urin. FRO RPHI E D HLOR L HIDR T.I!J. DIAG 0 IS OF MORPHI E POI 0 I G. 87 took tho fir t powder, became speedily comatose and cyanotic, and in a short time expired. A young physician prepared a olution of I gramme of morphia in 20 C.C. of water, to be used for ubcutaneou injection, and had it labelled (( suo nomine." His yringe h Id about I c.c., and he intended to inject one tenth 01' one fifth only of its conten 5, 0 as to admini tel' 0'005 or 0'01 gramme of morphine. But the first time he u ed the ring he forgot, after filling it, to fix he check-screw, and on pI' inD' down the pi ton injected the whole con ent , 0'05 (1 of a grain) of morphine, under the patient' kin. He had carcely left the hou e when he wa hurriedly 'ummoneu back, to find hi patient unconsciou , with feeble re piratiou and small pulse. The mi take wa. imm diately recogui. ed, and fortunately was not followed by any injnriou' effect upon he patient, though it wa not without detriment to the phy ician's reputation. Th DIAG 0 IS of morphine poi oning is ea y if the corpus delicti happens to he di cov red. reparation of opium are recogni ed by their characteri tic ouour, if this ha not been de troyed by the addition of 0 her sub tance . 'I he meconic acid reaction al 0, to which I have already r ferr d, may b employed to detect the pre ence of opium in an 'olution that may be left or in any matter that ha been vomited. In such a ca e the vomited matter bonld be filtered, th fil rate concentrated if nece ary, and tben fe, drop of a olution of the percblol'ide of iron added. 11 tbi can be done vel' quickl, but the ca e may run too cute a cour e to allow time for the inv stigation. F iliug a ru~twor hy account of the preceding hi tory of th pa in, and in th ab ence of the corpu delictI:, poi oning b morphine ma be mi -taken for that which 1'e ul from larg do e of alcohol, of cbloral, carbonic o ide, or coal ga . e' rly 11 the mptom ,hich ha e b en de crib d ar pre ent in poi oning from th e ub-t nc : one onl i u ually ab nt-the strongly 1nark d m.yo i, or con raction of the pupil, hi h i in ariably pI' en in morphine poi onin , nd which pa e off only in he la t aD'. It i probably due to condi ion in the btain, and not dep ndent on local cion uch a i produced by ph poi 0 ing bre th b Dr OF MORPHI E POlO I G. are-In be .35°. TREATMENT OF CA~E OF MORPHINE EOI I G. 8D fatal, an average lowering of the blood-pre sure from 129 to 91 mm. of mercury has been noted.1 And my a i tant, H. Heubach, under the ame conditions, in ix experiments on dogs, noticed that the pul e ank from 120 or 130 to 42.2 It ha been further urged again t m view that the diminution of the blood-pressure arose from he animal being bound down for hours, but I could easily prove that, by tying an animal down for a given period, the blood-pre ure is only slightly affected, and in tead of being dimini hed i inc1·eased. In the TREATMENT of cases of poisoning our fir t bu iness is to remove any poison that may be pre ent in the tomach. In .lighter cases vomiting may take place spontaneously, and may be promoted by tickling the fauces. In more severe ca es morphine very soon completely suspend the excitability of the nerve-centres in the medulla oblongata, and even metics produce no effect. It i better not to waste time with them, but at once to wash out the stomach. 0 other proceeding is of any u e in these ca e . If strong emetics, especially the mineral one , remain in the stomach and become gradually ab orbed, they help to Ie en the strength of the patient by still further lowering the activity of the already enfeebled heart. Many of the unsucce sful ca es which have be n recorded give the impre ion that the powerful emetic employed had ouly int n ified the poi onous action of the morphine. The injection of apomorphine, which has be n recommended as an emetic, and which even in mall do e act ry energetically, ma still cause vomi lng, but it i a eriou que tion whether he combined effect of two such extr mely low ring agen s does not render he patient's condi ion more critical than before. In ca e of poi oning by other officinal alkaloid TANNIC ACID m y be admini ered for he purpo e of rendering th poi on still in the tomach less oluble, but it i of little ervice in morphine poi oning. I C. Binz, "U b r den arteri lien Druck b i Morpbinvergif un " 'Deut cbe moo. ochen chr.,' 1879, s .613 und 627; und 1880, . 149. S Reub ch ' rchiv f. exp r. Pathol. und Pharmak., 1877, Bd. viii, .38; . Fick,' erbandl de Congre e fur inn. Med.,' ie baden, 1 86 s.92. 90 D~ OF RTIFIOIAL RE PIRATIO • If, for pump mu a h d ou paD' pIne ch. . mmluD hUll r • Eine del' 'in tlich n ,319. of how iO'n of failing, imRTIFICI L RE PIRATIO • hould only be attempted it, In a ea e of poison- ARTIFICIAL RE PIL{ATIO • 91 b ck) and an as i tant should bend tbe thigh firmly upwards o a", to relax the abdominal parietes. h11 t adopting the e variou mea ure for producing artificial I' piration) the maintenance of a free opening for the pa age of air to the lungs mu t not be forgotten. Draw the tongue forward as far a po ible) fi it in thi po ition) p-ither with the foreep ) or in default of the e, b a thick thread pas ed through it; pa s the index finger into he phar nx, feel for the epiglotti ) and pll h it a high up as po - 1 Ie. 'J'he following method (Heiburg) i generally to be r commended:- n a i tant stand in front of he patient, lac bis thumb on the upper jaw close to tbe no e) and curving hi finger. on both ide behind the angle of the low I' jaw) pull it vigorously forward. By pulling the jaw f rward in thi way he tongue and hyoid bone are al 0 thrown forward; the epiglotti , owing to the ligament b tw en it and the hyoid bone being put on the tretch) is aLo drawn forward, and the pa age to the laryn i k pt free. Thi ha been proved by experiment on dead b die. It ha been found that artificial re piration i not ufficient 0 effect the re-establi hment of the HEART'S ACTIO when its impul e i no longer perceptible.l on equently in all ca of poi oning of hi character pre ure Olu t appli d to the h art in uch a wa that it may be alternatel rnp ied and again fiUe wi h blood. In this w y th circulation 1 tarted: the heart begin one more o contract, and th l' pirator c ntr which wa almo t mpl ly paraly d) receiv fr b timulu froUl the bio that p ~e to it. In the v l·iou. treati d aling with rnorpl1ine poi oning the pplication of all ort of count r-ir1'i an 0 the kin is r commend a an importan p rt of he rea m n ) but It count r-ir1'it nt are of doubtful value when he pa j n) cond i ion i 0 critical. hi brin me to a point in the rea ment hi h i carcely r refer1' d 0 in l' a i e on poi omn ,name]', the value 8 a re orati e, of AR'I'lYleJ L W R TH co '1'1..: 00 LY APPLI D to he pa ient' body. 1 Bobm,' reb. f. exp 1'. Path. u. Pbarmak.• I 77. Bd. viii B.6 . E F THE W H.I B. TH n inquir D OLD DOUOHE. ar he m a appli d bon i f'cam in uffich ime.2 EFFECT OF TROPI E I ORPHI 93 The action of the central n rvou tern mu be main-tained by th internal Admini tration of '1'1 ULA T I refer in he fir t place to trong hot infu ion of tea and coffe. They contain two timulant, caffeine and an t romatic ub tance.1 If caffeine in MODI~RATR do e ubcutaneou ly injected into animal it produce a gen ral and active re Ie ne. , a more rapid and deep l' re piration, increa ed pul a ion of the heart, increa ed blood-pre ure, and a ri e of temperature. 'I'he e effects were rikiDgly manife ted on doO' suffering from poi oning of a imilar natur , namely, that cau~ed by alcoho1.2 hould there be danger in delay we mu t uot he itate to mploy the most powerful of all internal timulantsA'I'ROP] E. If a mall do e of atropine, a few milliO'ramme ,be ubcutaneou I injected into a dog in which, amonO' t other ymptoms following a large dose of morphine, there is greatly dimini hed blood-pre ure, the pl' ure will be increa ed wofold or more within a few minute. Thi i due to the greatl increa ed number of pul ation ; the beat of the heart are trebled or quadrupled, owing to a temporary paraly is of the cardiac branche of the vagi. The e branche of the vagi are the inhibitory nerv of th heart; they serve principall 0 reli ve he br in. If, in con equence of any timul tion, th h ar drive the lood too largel and too violently into the unyi lding cavity of the kull, the whole brain i hereby imulated. ut by TJ ULA'fl G he va i a slower movement of th hart' ac ion i produced, and one cau e of the exc of blood in h brain i removed. By PAR LY I G he va i ju he oppo ite eff c i produced; a quick l' mo emen , wi hout d fective contrac ion of th hear, take place, and the rt 1'ie become filled wi h blood. If the agu i. po ed nd divided, nnd i p ripheral lld timulat d with n induced curl' nt of 1m: po er, the he. r i immedi ely brought 0 a ,tand ill, or at Ie ·t th numb r of pul a ion icon iderabl dimini b d. If orne . Binz • B i di e zw' Kenntni del' Kaffeeh ndteil" 'ch. f. xp r. Path. u. Pbal'm~ k. 1 7 Bd. i , .31 . . Binz ibid" . 3 -3 . T PI E TIDOTE. In ha previoll 1y b n admini ter d to the animal, the CUlT llt on h ,O'u i nil. The atropine ha o p ra1 ed he end of th aO'u that it is o conduct, any timulu to tbe mu cular i. ue 1 nr ther fore, why atropin increa e he bloodnorm I condi ion, or les ened not overpower or re train pre ure, a i he cave with oth r 0·01 gramme oon we notice ATROPI E A A A 'rlDO'l'E. 95 ing the hremodynamometer it can be easily shown from the tracing on the kymograph that the increased number of pulsations corre ponds to a doubled arterial pressure. Here is such a tracing from a young dog weighing 2580 grammes.1 Its blood-pressure was, by the injection FIG. 2. A.tropine injected------- <::> r-of O' I 5 gramme of morphine lowered to 60- 0 mm., the pul e wa 40 a minute, n irregular. eventy cond . Heubach " nta ni rnu zwi chen orphin und tropin, , rcbiv f. expel'. Pa h. u. Pharm., 1877, Bd. viii, 8. 40, Pharmakol. In t. Bonn. LUE F E PERI E T racin commenc done £tel' for STEYOR I E A A A TIDOTE. 97 were fully dilated, the heart-sounds normal, the pul e 80, but the patient was still comato e. Afterward the nervou sy tem gradually recovered its sensibility to external impressions. The following morning, twelve hours after the administration of these large doses of atropine (altogether 21 times the German maximum dose I), the condition of the pulse, pupils, and respiration was normal. There was no mention of headache, but there was tingling in the finger and toes. ome hours later the mydriasis reappeared and 10. ted for some days. Thi is only one out of many cases recorded here and abroad.l There are cases, too, that give a different record, but they were improperly managed and have been obscurely described.2 There is nothing specially characteristic in cases of poisoning by any of the more recently introduced oporific ~ such a chloral hydrate, &c., with the exception perhaps of paraldehyde. In these case it is only the previous history which can help us to a diagnosis. The same treatment must be adopted as in ca es of poi oning by morphine. Luch inger has shown that 8> heart, the action of which has been paralysed by any of the ordinary cardiac poisons, can, in the early stage, be stimulated by atropine to renewed and often to vigorous contrac ion. This effect is not in his opinion dependent on the removal of any ob truction to the action of the heart, but i due to it direct stimulation.s Liebreich has specially recommended STRyeR 1 E a an an idote for chloral. The idea was suggested to him by ob erving the beneficial effect of chloral in a ca e of rheuma ic trismus and tetanu. He experimented upon a rabbit and confirmed his hypo he i that the conver e would prob bly hold good.' 1 John ton, U Cases showing the Effects of Atropine a an ntidote o Opium,'" ed. Times a.nd Ga.z.,' 1872, p. 269; 1873 p. 175. 2 Compare C Archiv f. klin. ed.,' 1887, Bd. xli, s. 174. I Luch inger, CArchiv f. exper. Path. und Pharmak.,' I I Bd. iv, . 374. • O. Liebreich, C on taber. d. Berl. kad. d. is en h. I 69~ .872 • 7 98 TRYOB I E A A A TIDOTE. It may be O'ranted a theoretically possible that strychnine can act ben fici lly in chloral poi oning. Chloral depresses the vaso-motor centre in the brain j trychnine stimulates it : 1 the former dilates the arteries, the latter contracts them; th former lowers the blood-pressure, the latter increa e it. In the narco is induced by chloral the e citability of the respiratory centre is lowered in an extraordinary de ree j in trychnine poi oning it i just as powerfnlly timulated. The re ult la t mentioned can be seen in any anim I previous to the appearance of the spasms; the re piration become more frequent and more profound. hat bearinO' the e f ct -gained from experiments on animal -m y have on the point under di cus ion must be d cided by furthet' ob ervations on the human subject. hil t making such observations it hould never for So moment be forgotten that powerful dose of strychnine are uncontroll bl in their effects, as we shall learn more fully 1 er on. I, for my part, should only have recourse to trychnine (0'002 gramme, i. e. -h of a grain, a few times ubcutaneou ly) if, in a case of great danger, neither a hot b th ith cold douche nor atropine was available. yer, c tudien zur Physiologie des Herzens und del' Gefiisse," i zun richt d. k. k. d. d. i ensch,' 1 71, Bd. lxiv, s. 657. 2 .Ohri tiani, c onatsber. d. Berl. kad. d. Wissensch.,' Feb. 17th, 1 I. VI. Pota sium b1'omide-Its discovery and introduction into medicine- Experiment with it on healthy individ1.lals- econdary ~Uects-Sodium b1·omide-.Ammoniurn bromideZinc oxide-Its '/.tse in the1'apeutics-Poisonous actionExpe'riments with it-Othe1' officinal prepa1'ations of zincHemlock- Its prope1,ties-Death of Socrate from hemlock - Jubsequent experience of its effect on man-Experiment on animal -Therapeutic value of hem'zock-Oonium hydrob1'omide-Hemlock sometimes mi taken f01' culinary he1'bs-Water-hemlock (Cicuta virosa)-Ou1'a1'e-Its origin - tatements ofHumboldt and of other travellers-nlu tration of it general action on warm-blooded animals. Analysi.~ ofit effects on the frog-Ou1'wrine- Variablene of curare-Its therapeutic '/.t8e, WE now come to a group of remedie differing entirely as to their source and in their outward appearance from the cerebral edative which we have previou ly con idered, but agreeing with them in ome mea ure a to their effect . The e are the bromide, of which POTAS IU BRO IDE i the one mo t employed. Its compo ition i KBr; it con i ts of colourle s, cubical, hining cry tal, which are not decomposed on expo ure to the air. It i oluble in 2 parts of water and in 200 part of alcohol. ben a solution of it in water to which a little chlorine ha been added, is agitated with ether or chloroform, ei her of these will on epar tion exhibit a red colour, hich i due to the liberated bromine. Tar aric acid added o it in exce s give, after standing for ome time, a white cr talline precipitate of acid tartrate of pota ium j the , upernatant fluid contain h drobromic acid, he followin decompo ition h vin taken place: Br+C4,H60 6= C H50 6+HBr. 100 POT IU BRO IDE. he phy ici n ha b en in a very different pre iou 1y h c e ith regard to pil ptic a t ck , for in former ime there f w year after the di covery of bromine in 1826 by BIard, n apoth car of Montpellier, the u e of the pota ium It a medicine came into great vogue as a remedy among rench phy ician. Being chemically similar o iodine, the newly di covered element had a signed to it he already well-known therapeutic properties of the former, and it a u e in crofnla, syphilis, and for glandular wellin , uch a goitre. On account of the corrosive ffect of pure bromine, the potassium alt, corresponding to that of iodine, was prescribed, and wa taken internally in quantitie mounting to 30 grammes (460 grains) daily. o improvement took place in the above-named diseases under he admini tra ion of the bromide, but its effects in the ell' e do e on the brain were recogni ed. tupefac-ion, giddine ,heavin of expr sion, difficulty of speech, ag ering g i, dimini hed sen ation in the extremi~ies, boli ion of r flex c ivity in the phar nx, were the only re nIt of he e herapeutic experiments, which, in I 50, Pnche 1 in Pari ermed Cf ivre e bromurique." Huette no ic d uch a ompl e abolition of reflex activity in the ph l' n , ha h ugge ted that the dru might possibly be of ervice in urgic 1 operation . rly I 5, ir ocock recommended bromide ium for epil p y ; 2 but for ten ears it a rarely e, nd i a only after the 1 p e of another ten and after car fnl tud of the records of it er I r number of ca e of that di ease-a o ari hIe, nd therefore therapeu ically so decep-i h th u efulne of he l' medy as unqu tionably emon tr ed. h80 time h f .24' Hue te)' az. TRE TME TT OJ!' EPILEP Y B POT IU BROMIDE. 101 eemed to be little or no po ibility of mitigating this frightful di ea e. In the institution at Stephan feld, in 1 ace, thirty evere ca es of epilepsy were ystematically treated with large doses of bromide of potassium with the following result. In 23'3 per cent. the attacks entirely cea ed during its use j in 40 per cent. the number of attack decrea ed by at lea t one half, in the majority of the e cases by more than Ol1e half j in 26'6 per cent. improvement was slight or doubtful, and only in 10 per cent. could it be aid that no effect at all was produced.l .A further erie of twenty-two ca es wa divided into two groups. To one half ODIUM BRO IDE only was given, to the other half only POTAS IUM CHLORIDE. After ten week' u e of the e medicines to the amount of 5 gramme (75 grains) to each patient daily, the odium bromide had very noticeably decreased the attacks in several of the eleven patients, whilst no distinct effect wa observed in the patient treated with potassium chloride.2 imilar re ults were reported from the institution at Pforzheim.3 Bennett, of Edinburgh, reported hat in 2'3 per cent. of the patients under treatment with pota ium bromide the number of attacks increased j in 2·3 per cent. no change at all could be perceived j in 3 per cent. the attacks greatly decreased in number and in violence j in 12 per cent. they entirely ceased as long as the pota sium bromide wa tak n. In addition to thi, the effect which pota sium bromide ha in many ca e of disturbed sleep is ea ily e plicable. enator informs u that ven he leeple ne and re tI ne of fever are reliev d by it to a greater e tent han by any other remedie. Its value ha been proved aloin many form of rigeminal neuralgia. It hI! been 1 C. S rk, I All . Z it chI'. f. P ychiatri i, . 29i. 'E. . eguin records imilar tatistic, ~w York Therap utic 1 c., I 78, 8th February. In oppo ition to hi ee . ander Cen-b ·albl. fiir die m d. i.,' I 68, .817. 3 t, I rch. f. P ych. und ervenkrankheiten,' 1875 Bd. v • . 24· " H. Bennet, ' Edinb. ed. Journal,' 18 I, vol. vi, p. 706. • enator, I Der fi berhafte Proce s • Berlin I 73, . 2 7. 102 ITH POT IU BRO IDE. e crib pecific for the vomiting of preg-nancy. I Clinical ob rvation of the effects of potassium bromide had, a i 0 often the ca e, outdi tanced and preceded 'ci ntific inve tiga ion, for the re ults of the latter remained confu ed and contradictory. Thi wa due to various 'au e. In th periments the effect of the POTASSIUM con tituent wa either not taken into account, or the result weI' ntire1y attributed to it. The experiments were made on lMALS which, in compari on with man, are in general much I en itive to he action of narcotic, at lea t so far he c I' bral hemi phere are concerned; the experiments, mol' 0 er, re m de on HEALTHY animal , without reflecting that a heal hy nervou sy tem may probably be Ie s in£ luenc d by ny edative remedy than one which is morbidly xcited; and finally, in many ca es the dose mplo ed in the experiments was far too mall. rather length eri of experiment from Kiel-revi ing all the previou inve igation in the light of the increa ed experim nt 1 and clinical experience that had accumulated in th meantim - howed, how what had been e tabli hed in the di ea ed, applied to the healthy, and furni hed an expI na ion of ome of the peculiaritie which had been ob erved in he ca e of nimal. rom 10 0 IS gramme (ISO to 225 O'rains) of potasium bromide dminist red to healthy oung m n in a 1 do , or in the cour e of a fe minu e, gave o oppre ion nd f eling of warmth in he tomach, liv ion, ligh nau ,nd liquid evacu ion ; further, o front 1 hache of a dull, he vy char ct 1', a though th compre e ; the ment I facul ie w re con-d n h po of thou h ob cure. Thi d for e era1 hour . peech a low and nd 11 ble 1'e mi plac d; la itude I'd impre ion re ob r ed, but h ordin r n rcotic. Th roo of he throa ha 10 t heir reflex EOO D RY EFFEOT OF po'r IU BRO IDE. 103 activity; irritation of any part of the fauces did not produce the slightest tendency to vomit. The temperature was lowered from 0'50 to 1'20 C. (0'90 to 2'1 0 F.), and the frequency of the pul e, which was irregular, IS to 37 per cent. ; the arterie were soft and ea ily compre ible. The effect on the temperature and pulse was most marked in the second and third hour after the dose had been taken. Control experiments with potassium chloride howed that the effect on the heart wa always largely due to the potasium. Later on we shall have yet to consider in detail the very marked effects which the salts of potassium exert upon the heart's action. ODIU BRO IDE, taken by the same individuals in the same manner a the pota sium salt, produced the same effect on the nervous sy tem, but not on the pulse and temperature. On animal it was 801 0 distinctly proved that the sodium salt dimini hes the reflex excitability by direct action on the nervous centres. The administration of pota inm bromide to dog Ie sened the electric excitability of the cortical ub tance of the brain.l Inconvenient SECONDARY EFFECTS ari e from the prolonged u e of potassium bromide. Foremo t among these are disturbances of the digestive function, but they can be modified or prevented by giving the medicine in a large amount of water, and not on an empty tomach. Catarrh of the re piratory pas ages is developed or intensified by pota sium bromide, nd may a ume a serious character, owing to the simnltaneou abolition of the reflex activity; mucn accumulate, expectoration is impeded, and the bre th becomes offen ive. The mucou membrane of the eye, no e, bladder, and urinary pa age may 801 0 be affected. In the majority of c ses cutaneou ruption appear j he mo common i AC of the calp, which from bing punctiform m y become pu ular.j The bromide ha been detected in the ecretion of the pu tnle j 3 he produc ion of the e is 1 P. bertoni, reprinted from' Lo p rimentale,' I 81. 2 ViI ' ierteljahrscbr. f. Dermatol. u. yphilis' 1875, Bd. i, . 17. Kapo i ha n acn in a child at the brea t, ho e mother a takin o ium bromide, •Ther peu. onat heft ,. 18 9, s. 468. 3 Guttmann,' rch. f. p' thoI. Anat.,' 187 , Bd. lxxi, .541. 10 ETHOD OF D I I l'ERI G POTA IU BRO IDE. . 3 und 6~. die rheini ch· tf·· u to the bromine only, for th yare developed 801 0 by the t 0 otb r officin I compound, odium bromide nd ammonium bromide.1 The acne m y develop into boil. .L. ettIe-rash, imple and nodular erythema occur j these all di appear on di continuing the medicine. neral c chena may be developed by an immoderate use of he bromide. The symptoms a sociated with it are atroph , a allo compIe ion, commencing paralysi of the e trellitie, 10 s of e ual de ire, diarrhwa, trembling of the limb, foul and coated tongue, want of appetite, mental pathy, eakne of memor , dilatation of one pupil, lateral deflection of the uvula, and even delirium and hallucinations. Th mp oms are u ually pI' ceded by inten e headache. There i gr t diver i y a to individual u ceptibility in the d v lopment of unplea ant effects. Recovery, a a rule, gen raIl t ke place, e en from evere form of bromism. c of hi kind ha been reported 2 in which, after Jar do e of pota ium bromide had been taken £01' about hr e ear to relieve leeple ne , m rked cachexia was de lop , hich, ho ever, di appeared after six mon h8' m nt. ith l' g I'd to he I T TIO of pota ium bromide pilep y-the di ea e in hich it beneficial action i so ur n 1 n d d-the folio .n method, b ed on the re ults f it n in ry large number of ca e , may be recom-m n ed for adoption: s_a 10 p r cent. olution of pota ium 1'0 i in l' m y b pre cribed a foUo B: during the fir hI' e table- p onful d il , mornin , noon, and bout half n hour before meal j in the four ble- poonfnl , di tribu d equall over er t k D imm di ely befor or £ er eating; k fi 1 - po mul d ily, and 0 on from h qu D i ein incr db on t ble- poonfnl t bl - poonful d il ; 0 h durin he fir eek bl - poonful m be giv TI, during he econd -ei h , durin he bird hir -five: more han EFFECT' RESULTI G FROM THE OTIO OF POT IU. 105 eight table-spoonfuls a day ought not to be given} and this amount must be discontinued or diminished if it seems to cau e drowsiness or mental dulne . Should such a condition occur} as may be the case in isolated instances} even ith seven or ix spoonfuls} the quantity must be reduced. But if the attacks cea e when three table- poonfuls} for example} are taken during the day} then the dose must not be increased in sub equent weeks} but mu t remain at three table- poonful . Only on the reappearance of an attack} or if there are warnings or indications of one impending} hould the dose be increased by one table-spoonful daily} until such a quantity -it may be four} five} i} even} or eight table- poonfuls daily-has been reached as put an end to their development. If for about three month here have been no attacks} the number of doses may then be as gradually diminished as they were mcrea ed. After the daily amount ha been diminished to hree table-spoonful} it will be prudent to con inue this do e for two to three month longer j the quantity can then be decrea ed to two table- poonful dail} giving his for perhaps three month} after which the medicine can be left off altogether. If he attacks recur} he me plan of treatment must be l' ne ed. In many ca e patient cannot dispen e with the pot ium bromide at all} nd mu t for ear habitually take a mall quantity-two} three} or four table-spoonfuls of the olution j otherwise the attack oon return} and with ev n greater severity than before. In the ca e of children between ten and sixteen years of age we m y commence wi h three table- poonful } but must not go bond i table- poonful at the mo t in the twentyfour hour . ith childr n under ten y ar we may begin ·th t 0 table- poonful } and ad ance to four or five tablespoonful in he wen -four hour. In the c80 e of very young childr n he amoun mu t be ill further dimini hed. If pot ium bromide ba' b en taken for a con iderable ime} or e en for a few donI } b u c p ible per ons, it h be n ob erv d to affec he HEAR'r unplea antly} the pul e becomin feebl} irr aular} nd in ermittent. Thi i doub Ie du to th pota ium} \ bicb} con tituting 33 pre n . of the 801 J m y very l' adil , giv n in tb 106 ODru , 10 IU , D 0 LOIU BRO IDE • large do above mentioned, and in a form 0 easily b orbable, e rt it d pres ing influence upon the heart' action. or thi l' a on omu BRO IDE i preferred by many ph ician.1 According to the erman Pharmacopreia this is aBr, containing no more than 5 per cent. of water of crystalIi tion. It i a hite cry talline powder, undergoing no change in dry air, but somewhat delique cent under ordinary circum tance, olubl in one or two parts of water and in fi prof lcoho1. BRO IDE, H4Br, is also officinal. It is a white cry tHine powder, readily oluble in water, less so in alcohol, nd ublimes unchanged on he application of heat~ Thi pI' P l' tion contain a larger amount of bromide than an of th other compound -namely, 81'6 per cent. It is,. how 1', the mo t a ily decompo ed, for by mere exposure to he ir it oon becomes acid and yellowi h-effects due to the form tion of hydrobromic acid and bromine. There i i to be one drawback 0 it-n mely, that it exerts an injuriou influence on th dig tive function. nother point to be borne in mind is the endenc, hich the ammonium n tituen i aid to po e , to produce pa modic con-raction . t no pI' ci e inve igation eem to have been made 0 how f l' he pI' nee of 18'4 per cent. of mm nium in bromide of ammonium may mo ify the effects of bromid in h tr atm nt of di ea e. LOlU BRO ID al 0 h been found to act a a edati e Oll h m tor, n ory, an r fle cen l' in the br in and pinal cord, bo h in h 0.1 h nd di ea ed condition .2 The lin er of un t r-on- he- tein, ne r Kreuz-n ch, con in in 7'5 gr mme 0 line m tter, di oIved in 10 Ii r f r, 0'75 r mm f odium romide nd 1 0 of m Q'lle lum bromid . I i oub ful he her 0 m 11 II m unt of bromi c n ha 1 effect hen th £01' ba h. Th moun contain d in th pring nJ in larO' r-th i to , of 292 I T. J. Btl on,' L ce , Eul nbur u. ut m . ' I 73 .436. • I 1. a. Phy iol. u. . ensch. IMPURITIE • 107 grammes of saline matter contained in 10 litre of water, more than 2 grammes consist of sodium bromide. Intentional adulterations of these salts, lessening their therapeutic value, are so improbable that we need not con-ider them. The tests given in the Pharmacopooia are sufficient to detect such impurities. On the other hand, the bromides may, from being imperfectly prepared, contain ome bromate, or even hypobromite-that is, compounds of bromic or hypobromous acid, KBrOs or KBrO. In acid media, and consequently in the stomach, bromine would thereby be liberated-a result neither contemplated nor desirable. These impurities, as I here show you, may, if present, be detected by adding a drop of diluted sulphuric acid to some powdered bromide on a white porcelain slab, when the salt immediately becomes yellow. Hydrobromic acid, together with bromic acid or hypobromous acid, as the case may be, i liberated by the sulphuric acid. They act on each other, and bromine is set free. In the first case we have-sKBr+ KBrOs+6H2S04=6KH °4+3HzO+3Brz; in the other- KBr+KBrO+2HzS04=2KH 04+2HzO+Brz· Pure bromide does not give this reaction, as the re ul ing hydrobromic acid, which is alone formed, is devoid of colour. Zinc, in the form of ZlllC oxide, ZnO, and of zinc ace ate ( ",HSOZ)2 + 3H20, i ub tance which ha been emplo ed from a very arl period for much the ame purpo e a pot sium bromide. Zl eI ° JDU ,Zincum Oxidatum, oxide of zinc, i a whit , of ,amorphou powder, becoming pale ellow hen hea d, in oluble in , ater, but oluble in dilute ace ic acid. It wa 108 Zl o IDE. form r1y named a1 0 Flore zinc " 'hilum albtlm, Lana ph'lo ophica. For when the metal is melted in open vessels th 0 idi'e urfac take fire, burns with a dazzling white fl m, nd ive off den e hite fume. Thi phenomenon known long ago to Dioscorides, and compared by him to the form tion of 001. 1 o i e of zinc wa largel u ed formerly in the treatment of EPILEP y nd other di ea e of a imilar character, especiall in oung children, in whom opium and morphia are inadmi ible, It u to be called the br in opiate of chil hood, Rufel nd reckoned it among the anti-epileptic specific if given in large do e , and it continued to be used for long p riod. t the pre ent day oxide of zinc ha be n uper e d by newer remedie, especially by pota - ium bromide; but ven at the pre ent time communication occ ionally ppe r which e tol the effic cy of 0 ide of zinc a en nti p modic,N t mpt have been made to e tabli h thi heoretically from the ymptoms produced by poi onou do ,and from perimental result , u tS I' late that chemi t whil t preparing flowers of zinc inc utiou ly filled he hole laboratory wi h the fume , an e.. perienc d, in con equence, difficulty in breathing, l' i 0, be d che, leeple ne , p in in the abdomen, vomi in cou hing, nd h avine of the limb. The v l' iO'o 1 until he bird da ) and he general eakne ill he third e k, h n compi te r covery took place. ibm l' give n ccount of e er 1 e h u tive E PERI-o H • BIG. The fir t made b Glauber in I' 165-, he other chi fl b "\ rn ck in the ear 11 of h m e fin en i n the me mp om ju de crib d. 1'fila a mini t red 0 ide of zinc i 1 . Pick • Z 63· im und n tieri ch en ZI 0 0... IDE. 109 to small and feeble dogs in dose of from 9 to 18 grammes, with no further result than painles vomiting.l highly cultivated, powerful man of forty-three years of age was seized every six or eight weeks with a violent epileptic fit. The reading of a medical treatise 51 led him to try oxide of zinc in gradually increasing doses j he took altogether in five months 195 grammes (3000 grains). t he end of this time, he wa pale, emaciated, and ment lly dull j he tongue was heavily furred, the bowels constipated, the abdomen distended, the legs redematous, the pulse thready and infrequent, and there was great bodily weakness. There was no vomiting throughout. During this period there had been no epileptic attacks. The medicine which had caused uch disastrous results was topped and the diet carefully regulated. In a few week the pa ient recovered, but the redema of the feet and the con tipation continued for some time longer j the epileptic attacks again returned with the arne intensity as before.s This case would be more instructive if oxide of zinc only had been taken, but being combined with extract of henbane and oil of chamomile, it merely shows that the amount mentioned could be taken in five month without producing PRE T injury. How far this may be due to the other t-v 0 drug cannot unfortunately be ascertained. A. ichaelis specially investigated the action of zino o ·de. He himself took while fa ting as large a dose as 0'36 gramme (5l grain ) j irritation of the tomach amounting to violent vomiting, and a general en ation of wearine 5, were he re ult. He admini tered ithin four months 72 gramme (1000 grain ) of oxide of zinc to a trong dog in its food, omiting, utter pro ration, trembling of the limb, and dulne followed, and the animal wa attacked by convul ion, which recurred daily for three month j it wa then killed, and gastro-enteriti as found to be pre ent. I Orfila, CL hrb. der Toxicologie' ueber on Krupp, 1853, Bd. ii, . 37· :I iedler, Hufeland' C Journal del' pra . Heilkunde,' I 31, . 65. • Bu e, C per s C ochen chI'. f. d. e. Heilkunde,' I 37, S. 302. 4 'cha Ii , CArch. fiir physiol. Heilkunde,' I ""I, s. 109. 110 P I 0 OU E:Jj'FEOT OF ZI 0 OXIDE. On e amin tion the metal wa found in all the organs, and e pecially in he brain. The following account i from Botkin's clinic1 at t. Petersbur . young man had worked for twelve years in a bronz fa ory, ·po ed to the fume of oxide of zinc; he graduall dev loped general cachexia, which was characteri by io] n irritation of the tomach and intestines, he ache, rigor, and cramp in the leg ; pare i of the ri ht ide of th face and of the corre ponding extremities follo ed. The patient tated that he bad left the factory a month b fore he came to the hospital; the urine, neverth Ie , till contained zinc. He was afterwards discharged, materially improved. In tb zinc mine of ile ia the workmen suffer from ob tinat catarrh of he air-pa sages and of the intestine, in con equence of inh ling he fumes or he dust of zinc o id , and thi i followed by general cachexia. fter ha in orked in the mine for ten or twelve year they of n pI' ent 11 the mptom of tabes dorsalis; pains in the loin , tenderne of he sole of the feet, heat and pricklin in he Ie , ith diminished en ibility nd nnmbne in i ola ed po , increa ed excitability of the cutaneous nd tendon refle e , fe tinating and c1um y gait due to dimini b d u cuI I' en ibility without atrophy or 10 s of e1e ric e ci bilit of he mu c1es, and finally a <lecrea e of IDO or po l' in both upper and lower e tremitie .2 perim nt on nim 1 h ve hown that inflammation, i h f ty d eneration of the epithelium of the kidneys, is no h l' ffect due 0 the poi onou action of zinc.s I i in re ting, from biologic 1 poin , to find that plant 1'0 on oil impregn ted i h c 1 mine (ZnCOs), and 1y b orb th 0 ide from th oil, owin to the cr io from he c 11- 11 of he root, 'thout their 10 m n b in check d. The 1 rge t moun of oxide i found in be m nd 1 a ,he 1 a in the eed; he e rmin e norm 11, n c n b ea n i hout injury. I L. Popo J' B rHn r klin. 0 h n chI'. I 7 8. 49. hI 0,' D u ch m . ochen chr., I 79. .20 und 221. . H pup I D u h m d. ochen chI'. 18 9 o. 38. From the r tory of Hug chulz. OFFICI AL PREPAR TIO S OF Zl O. 111 The amount of oxide of zinc in the ashes varies from o'5 to I per cent. olution of zinc alts so dilute even a 0'02 per cent. of the sulphate, have a very injurious effect on the growth of plants.l Chloride of zinc and sulphate of zinc, he former of which is u ed as an escharotic and antiseptic, the latter a an astringent in affections of the mucous membranes, have also been tried internally, and produced essentially the same result as the oxide and the acetate. 2 ZINCUM ACETlCUM, Zinci Acetas, which is sometimes administered internally as a nervous sedative in tead of the oxide, con i ts of colourles crystalline plates, of a pearly lustre, soluble in 2 parts of water and in 36 part of alcohol. dilute watery solution become dark red on the addition of perchloride of iron. It yields with solution of pota h a white precipitate entirely soluble in an excess of the reagent; this solution, if treated with dilute sulphuretted hydrogen, again yields a white precipitate. The oxide contains 80, the acetate 30 per cent. of zinc. s, however, the latter, owing to its ready. olubility, passe more rapidly into the ystem, its action i probably more energetic. Valerianate of zinc and lactate of zinc are, as remedies, ab olutely superfluous. Zinc oxide in the form of ointment i u ed a an astringent and timulant to mucous membranes and ulcerating surfaces. These effects are probably due to he fact that it is di olved in the acid secretion of the part, and then, like the chloride and the sulphate, forms an albuminate. Owing to thi a tringent action, zinc oxide ha been employed internally iu inte tinal catarrh. In uch case it i dministered in full dose of O' I gramme (I! grain ) every hI' e hour in combination with odium bicarbonate. It i fur her noteworthy that as a constituent of Li ter's dre ing zinc oxide ha proved to be an excellent anti- . Freytag,' .ttheil. d. Akad. Popp Isdorf,' Bonn, 186 , Bd. i, • 2. 2 H. L theby, 'Lanc t, 1 50 vol. ii, p. 23 j B. T a,' Il or ani,' pIe J ept mb r, I 81. . Oorradi r fer 0 thirty-four ca s of P i oning by the chloride and ulphate, 'Annali Univ. di d.,' 1 79, ol ccdv, pp. 197 and 3 6. 11 00 E. eptic. It pr vent the development of the lower organisms, Ie en ecr tion and k ep it free from mell, and promotes cica ri a ion.1 It beneficial local action in catarrh of the inte tin i probably due to the e propertie . Thu far we ha e been chiefl occupied with the consi. deration of remedie which ac as cerebral edative. We nm proceed to con ider another group which act more par-ticularly on other part of the nervou tem. Co I i the name of an alkaloid obtained from the seeds of 0 IU CUUTU ~ hemlock, a plant belonging to the ural Order Umbell ifer , and widely di tributed over G rman. It i a colonrle or yellowi h, oily, alkaline liquid, 01 iIi ed by heat, of a peculiar penetrating odour, h ving a pecific gravit of O' 8, and mi cible in all pl'oportion ith alcohol, ether, chloroform, and oils. It is oluble in 100 p rt of water, l' adily 0 in water acidulated ith h drochloric cid. It formula i 0 H16• H. Geiger In I a the fir to obt in it in a pure form. Within the 1 fe i h been produced ynthetically. 'd' 0 H ~ rl In, 5 5 0H_- OHR / OH,1'8 ransformed m. to pip ridin ~ C5Hn or H<~:=R~)OH2' and by the ub ti u ion of propyl, 0sH7, in hi., e obtain 0 H16• H or H< .OsH7- iH"')CH prop I-piperidine, or arti. fici 1 conin, hich i optic 11 a further proc b come optic By c i , n po . e e 11 the chemic n ph iologic 1 pI' per ie of natural conine. onin nd ammonium al , hemlock cont in ( 16'CHs ) and very little conydrine 1.0. ) bo h of hich ar ba ie ub ance. n n nci n nd f mon 1'1 In here is a de crip ion of he poi onou it c of hemlo k on m n. lode cribe in a Pet ' D. m d. ochen chr., I 3, o. 2". THE DEATH OF OORATE BY 00 I E. 11 affecting words the death of hi ma tel' b the poi on cup, he content of which were prepared virtually from the ttic KW~ElOV, which wa noted for its treng h. C( rito made a sign to the ervant who wa tanding by ; and he went out, and having been ah ent for some time, returned with the jailor carr ing the cup of poi on. ocrate aid, C You, my good friend, who are experienced in the e matter, hall give me directions how I am to proceed.' The man answered, C You have only to walk about until your legs are heavy, and then to lie down, and the poi on will act.' . . . . Quite readily and cheerfully he drank off the poi on. . . . He walked about until, as he said, hi legs began to fail, and then he lay on his back according to the direction, and the man who gave him the poison now and then looked at his feet and legs; and after a while he pre ed his foot hard, and a ked him if he could feel; and he aid, no; and then hi leg, and 0 upwards and upward , and howed us that he was cold and stiff. And he felt them him e1£, and aid, (When the poi on reaches the heart, that will be the end.' He was beginning to grow cold about the groin, when he uncovered hi face, for he had covered him-e1£ up, and said-they were his la t word -he aid: C Orito, lowe a cock to clepius; will you remember to pay the debt 7' (The debt hall be paid,' aid rito. (I there anything else 7' There was no an weI' to this que tion; but in a minute or two a movement was heard, and the a tendants uncovered him; his eyes were et, and Orito clo ed his eyes and mouth." 1 The scene here described has been often, wholly or 1U part, repeated, sometimes intentionally, at other time unintentionally; sometime for purpo e of in ruction,2 or through carelessness, or by mi take,S and orne imes wi h murderou intent.4 onng delicate woman took four dr chm. of uccu 1 Jo ett Plato, vol. ii, pp. 265-6, 1891. 2 John Harley, 'The Old egetable eurotic,' L ndon, J 869, pp.l 9. :I Imbert.Goubeyre, 'Recherche or la mort de crate par la cigu', Pari 1 76 pp. 65-123. 4 In De au, 1 61. Reported in the' euel' Pitaval, Bd. . 9 . 8 11 EFFEOT PRODUOED BY OJ. lEO M on oniin el' iftung, 'Deu che m d. Roy. c. Edin ur h 1 36, vol. xiii, n ha e been in iO'a d in of Ii er ure on he xp riment he more conii of h ngli h harmacopooia, a thin fluid extract con i ting of 3 part of the II' h juice of the plant and 1 part of alcohol. Twenty minute afterward nausea and intoxication came on; he dropped an ink tand which she h d in h r h nd, and wa unabl to walk; he wa then put to bed. The ymptoms increa ed rapidly, and in consequenc of h men al agitation the pul e 1'0 e to 120; the heart r oon, how vel', became ranquil, but the patient ,a incapable of moving her arm or leO' . n hour aftt:r t kinO' the m dicine mu cular par 1 i wa almo t complete; when a k d to pen her e, he found it irnpo sible to lift h l' Y lid. Pul e and re pir tion were regular. Toward th nd of another hour the ymptom subsided, and after th lap e of hree hour the po er to mo e, and the u e f the limb ere quite re tored. On the following day all hat l' main d a a light pain in the mu cIe of the leO' . m dical tudent, at a lecture where conine wa. handed round, ook prolonged niff of it. bout an hour afterW I'd , he b an to feel a can tan 1 increa ing wearine , p ially in h limb , whil t he till complained of he m II in hi DO ril, and of a en a ion of burning in the conjun tiv . hi rain wa quite ci aI', an there a no ign of m nt 1 xhau ion. radually ev re h dache and violent hro binO' in he empi c me on. T, 0 hour aft l' h on Iu ion a he Iec ur the ud n, who wa b hat tim incap bi of ny mo ment, wa put to b d. Hi h ff c ed, the hoI body wa hot, and ther wa profu e tinO'; 1achr rna ion al 0 app red. He could no 1 p; h r l' pid flo of ide , but he a 11 t 1'1 inc p bl of fi inO' an ingle one. B he follow-mornin a tb re a de id d improvem n . ligh ill l' dil in uc d per pir ion, but complet oon took pI c ,I re ul 0 erv d in m nim 1. Ther i I ill no de on f EXPERIME T 0 ANIMALS. 115 I inject at one do e 0'06 gramme of conine hydrobromate in 2 c.c. of water under the skin of a rabbit weighing about 1000 gramme. For the fir t fifteen minute no pecial ffect are ob erved. 'rhe re pira ion th n become quicker and more difficult, and i attended by general re tIe n I now inject 0'03 more; the animal can no long r hold up it head, which fall to the id, althou h, a ou see, attempt ar made to rai e it. The e efforts oon cea e, and the head re t motionle s on the table. The limbs are rela ed, the rabbit fall on its ide, make a few vain effort 0 raise itself, and finally lies motionle s. The diaphragm alone is till working, but the activity of thi mu cle oon cease , and in thirty-five minutes after the fir t inj ction death takes place, preceded by a few short general convulsions. Paraly i of the striated muscles commencing peripher lly, and at la t affectinO' the diaphragm, i the cause of death. The hort spa modic movement at the end are due to uffocation. That the e spa m are not more marked is due to the paralysed condition of the motor nerve. The motor impul emanating from the medulla oblongata 0 the peripher ) and developed by he timulation due to the pre enc of una"r ted blood, cannot now be tran mitted along the motor nerve) and con equen ly the violent mu cular action which accompanie ordinary uffocation does not ake plac . a rule, the pa ill are due 0 uffocation; but om anim 1 hen poi oned b conine are aff cted with eneral convul ion, althouO'h ar ificial l' piration i bein carri d on at h ime.1 J 0 explanation of thi can a et be gi en. It can be bown on h frog th t the rou cular paraly i i periph ral, or at I a t ha it b gin in that wa , and only reach the brain after a. time, or wh n 1 red e ar p. 3 3' Alb r •D nt ehe Klinik,' 1853,8. 37 . Ruling und alz l' ibid, 1 53, . 436. ollik r,' reb. fur pathol. Anat.,' 1856 Bd. , .235' L. an Pra ,. Journal fUr Pbarmakodynamik,' 1 57,Bd. i, . I j Gu man,' B diner klin. V oehen ehr.,' 1866 8.8,44,55,76,81 . Pre • reh. d Phy iol., 1 0, .40 j Hn 0 ehulz,' Z i ehr. f. klin. d. I 2, Bd. iii . 19 j ehulz und E. Piper, im' reh. f. e per. Path. und Pharm. 1 Bd. xx . 149. 1 J. H. einbiiu lin, •Doetordi sertation' unter Leitung on R. D mme, Bern, I 87 s.61. 11 THER PEUTIO U E OF HE LOa • t k n in quick n rv and .1]1. in D ut chland • CONI E HYDROBROM TE. 117 It might be upposed that any uncertainty as to its action would be obviated by u ing pure conine, and this has, therefor , been made officinal in some pbarmacopreia j the alkaloid, however, bas not ucceeded in e tabli hing itself. This may be due eitiler to it gradual decompo ition when exposed to the air, to its volatility, or its unpleasant odour, or possibly it doe not really possess the special value which has been claimed for it. It was so rarely used that in 1882 it cea ed to appear in the German Pharmacopreia. orne years ago CONINE HYDROBROMA'fE, C H17 •RBI', was introduced into therapeutics. It is a colourless salt, fairly table when expo ed to the action of the air j it consi t of fine rhombic prism, and contains 61 per cent. of conine. Thi preparation has all the poisonous and therapeutic propertie of the pure alkaloid, together with some advantages j it i table, does not volatili e, and when administered Bubcutaneou ly does not greatly irritate the kin like pure conine, which acts in this way very much like ammonia. Two recent ca es are instructive.l bo seven year old wa uffering from severe rheumatic tri mus and tetanu. The experiments of H. chub and Peiper having hown that the pa m cau ed by brucine are controlled by conine, R. Demme admini t red thi drug to him. fter everal ubcutaneou injection of 0'0025 gramme (about -lo of a grain) the pa m cea ed, and the reflex activity was lowered. The flow of aliva was increased, re piration became more frequent" thou h irr gular. The boy recovered. 0'0475 gramme (-to of a. rain) of conine hydrobromate wa u ed within five d y . bow ten year old w uffering from raumatic ri mu an t t nu following a bi e of hi forefinger. Treatm n i h conin wa followed by a. d cid d deere e in the frequ n ura ion, and violence of the t tanic attac ,and at la b heir n ire ce stion for thir - ix hours. The boy died, hm ever, from ten ive pneumonia, from which h wa uff ring before he c me to he ho pital. i hin for y-ei ht hour he had t ken 0'095 gramme by he mouth Hemlock," dico-Chirurg. Tran action ' London, I 74; E.. urn 'Tr n acti D d. 1 R. D mm Bericht iiber da 18 6, . 6, bis 63. 11 n 0'1 ju I ... TRODU TI OF 0 IU I TO FOOD. reare, oon r-hemlock or '0 bane, beinO' d adl oi on.2 ho pit 1 .279· OURARE. 119 un RE, the outh merican arrow poi on, a dry c.. tract omewhat liko opium in appearance, of a ark brown colour nnd a bitter ta t. The Indian of th outh m rican tropics prepare it-a . von Humboldt and oth l' I ha e de cribed at length-chiefly from th bark and ap-wood of ttrychno toxife'ra, cogen ,and chomb-urgkii. The add al 0 portions of a con iderable number of oth l' plant, believing, quite without reason, that the e 801 0 are ential to the excellence of the preparation. rrow poi oned i h curare were fir t brought to Europe in 1595 by the EnO'li h admiral Walter Raleigh. The Indians on the Orinoco, on the ... mazon, and in Guiana dip he point of th ir arrows in the fre h e ract, nd 0 u e them in battle or in hunting game. (( I know the white men under tand he art of makinD' oap and the black powder, but the mi fortune i that it make a noi e nd frightens the animal if the hot mi e hem. i h u the art of making curare i tran mitted from father to on, and it i better than an thing that you cau make over there. It is the juice of a pI nt that kin quietly, and nobod know where the hot come from." 'uch are th 1 udator t I'm in which the Indian pok of hi pI' para-tion. When fresh it effect i vel'. pow rful. "L rg bird hit in the thigh b one of the poi oned arro\ die in from two to hI' e minut ,wild boar in from t n to el e minute. carpenter (of Humboldt' compan), a man of uncommon mu eular rength, incaution ly rubbed he curare on an arrow between hi finger, where he had rifling wound. He f 11 to tb ground ized wIth v I' i 0, hich con inued for half an hour. ortunatel he curar a a mil kind u ed £01' killing vel' mall gill. m n un ed ith th arrm f e1 fulne abou the he d and giddin ,so ba he i nnabl 0 tand j h n folIo nau ea, rep ated vomi ing, burning thir , and a £ eling of nnmbne about he ound d pot." Humboldt a a are f h fact that curar "become eak I' bran mt ion through damp countri " Thi i e uinocti. 1 end n merik " ppun,' nt r den Tropen J na lOA Tl 1 FOUR RE 0 W U -BLOODED till th en with he curare of commerce; but it i only its virul nee which i dimini hed, the character of the poi on remain he ame. inject into grey rabbit eighing about 2000 grammes on c.c. of water containing 0'0 I 5 O'ramme of curare. The h rt beat the rate of ISO, whil t the re piration. number about 120 in th minute. The pupil are of medium ize. In four minutes there is exces ive secretion from the I chI' mal gland. In ix minute the head falls forward; h animal make fruitle effort to rai e it. In seven minut he animal is lying on it ide; respiration is Ie s frequ nt, but till active: he pupil are unaltered. In nine miuute re piration i infrequent and very shallow; the e eballs pro rude, the pupils are contracted. In ten minute everal vel' hort re piration and quiverings can be seen: the heart-beat are still vigorou and above eighty a minute. In lve minu e he pupil are dilated, and there is no l' piratory movem nt. In fifteen minute , on e po ing the h art it i een to be ill bea ing vigorou ly at the rate of nty minute. The blood i dark, but become bright if i i a itate wi hair. h t i he cau e of thi I' pid and general paraly i ? e h ner e-centre, he motor nerve , or the mu cle the I' ff ct d . The problem i olv d by an periment on the frog,! , hi h ho ha TB TER I L ORG 0 THE OTOR ER E r he p l't fir t aff c ed b the ural'. In hi c iv nd i orou fr 0' I ha po ed he ic n rv in h upp r art of he thi h, and have tied f or 1 801' l' in one 1 clo to he kn -join. I no' inject u cutan ou 1 into the back 0'0001 ramme r in O' •• of t r; h h d OOll b gin if he bell-gla i r moyed, no longer re pira ion ha ce . d, nimal i A ALY I OF IT TIO 0 THE FROG. 121 timulat them, one immediately after the other, with a vel' feeble indu ion current j only he mu cles of th leg and toe of the ide on hich he artery wa ied contract j there is no movement whatever on the ide in FIG. 3.1 " h 1'e he poi on did not reach un ff c d. The commencemen, the vel' accompanying figur b me:min of hich i plained in h H DED P rtion indica the portion if, c d by h R L I indue d by he cural' . 122 A TIO 0 0 R RE 0 U OL"E A D ERVE • E ORY ER are I 0 he mo t r cent in e - curare. ater containing 0'7 p r. P tho U. Phal'm 'J I 90, Bd, ii o wh ther the coo1'dinO' to I J. Tilli , f . I. ha unaltered, even here a t1'onger timulation of the nerve, obt in d b approximatinO' tbe two coils of the battery, no Ion O'er produce any contraction. The paraly i affects oIly h motor en in f the nerves. If I e p e the f mol' 1 nerve in the pelvi , and a before ti hart r of the m ide at the knee, and then, iter inj cting th curar, timnl te the nerve, we ee that the imnlu of the CUlT nt can contraction of the mn cle of the 10 e1' part of th leer, but not tho e of the upper part. Tbi ar icular xperim nt mol' e peci lly demon kate h the TRU K of the nerve ha not lost it conductivity in ad ition to it irri ability; that, ther fore, the parts of h n rv nclo ed in he mu cle are tho e hioh are primaril ffect If the our l' ere not 00 powerful, and di not act too rapidl, might gain tIll more information from the ame animal; for if I imulate the crural nerve of the leg to hich he poi on ha had acoe s, and which i completely und r it inHu n e, nd orne hat increa e the trength of he g lvanic urI' n, liO"h con raction are ob erved in th other leg bioh i un ff cted by the poi on. But more h n t i, only e to pply he elec rode to, or nip wi h h forcep an 0 herwi e en'tive pot of the body which i und l' he inHu nc of he poi on, and the 1 g 0 which the pion ha nOL h d acce i convul d. The only plan tio of thi i th t he REFLE G GLI not bing par I d, a motor impul e de eloped here i tr n mitted hrouer he till uuinj I' pin 1 cord, the only pal' which ill abl 0 l' P n to the imuln. en ation, I' flex ·cit iIi , nd onduo i ity of he pin 1 cor , h refore, ill i, though h otorial nd-plate of the ner are p l' ]. d. pi r I' EFFECT 0 'l'nE BRA! • 123 per cent. of odium chloride (di tilled water act injuriou ly on l' c ntlyexpo ed ti ue; but 0'7 per cent. of aClobviate hi. ). Two preparation of mu cle with th ner n tached have for •orne time been k pt in thi olu ion, in th one ea e only the nerve being immer ed, in the 0 her, only he rnu cle. On te ting them lee rically the folIo, iug re ult is obt ined: both mu cle re pond equall w 11 when h lee-r e l' brought directly in contact with them, whil t the nerve re pond very differ ntly. On stimulatinO" the nerve of the fir t preparation the rnu cle contrac ; . imulation of he nerve of the other produce no re ul. In it the terminal of the nerv s are aturated with and para1 ed by h curnr absorbed by the mu cle from th olu ion, and, con quen 1 , no impul e i tran mitted through h m when he nerv - runk i irritat d. The.timulu meet with OUle ex raneous 1'e i tance in the nerve- ndin ,i hin the mu cl, n therefore doe not pa on to th mu cular i ue it If. '\ e have still to con id r the effect of curare upon the other important organ of the body. I i ot vel' ea y in exp 1'iment on nimal to accu-at ly determin the £feet upon THE BRAI. rom wha ha een ob er ed in animal and in man '\ e rna' conclude h cur 1'e ha onl a light effect upon he brain, an that he arne hold good of he entire m dulla. I' O"al,d the REA T and A CULAR SY TE , what wa ar ially d mon trated in the previou e prim Dt hold o d, but if tronger do e. continue to act for 'om tim, h pul e then becom ry fr quen nd '\ ak, and h blood-pre ure fall. The ff ct on th cir ula ion is e u e par 1 i of h gu nd con quentl r f he hr· h fall in the blood-pI' ur ari e from. imultaneous p ral . i of he v o-mo or n rv , hieh c u n ral dil ion of th t mic rt rie . h e aIre den in th rabbit th t 0 f h fir t o pp ar a iv ecre ion of th Ie eb l' 'mal hi , 11 n imjlar incr in h cr tion f th ali a nd of h urine in anim 1, 11a £t n b n d cribed nd plaiDed a being ue to imnl ion of he CR TO ERV. 12 EF EOT 0 THE TE PE 'fURE. OURARI "'E. 125 ubcutaneously under the back of a second fro cy • In tw nt five minutes it was compl tely paraly ed. Two day afterward a third frog wa similarly treated with the urine of the econd; in thirty minutes it was motionle . Then the urine of the third frog was transferred to a fourth j the re ult was the same as before. ThE! contents of the gallbl dder and lymph ac were harmless. Here we have the contents of the bladder of the rabbit which we previously killed with curare. I add to it one drop of sulphuric acid, and then a few drop of a concentrated solution of iodine and iodide of pota ium. A beautiful brown precipitate is produced, which how the pre ence of an alkaloid. All attempts to produce curare In a cry talline form have been hitherto unsuccessful. We only know hat its activity i due to an alkaloid, the formula for which, from it combination with platinum, has been calculatedI a 01 H35 • crystalline body i obtained on decompo ing CURARI E by heating it with acid, but this i iuactive. Pure curarine is extremely poisonous. For a rabbit w ighing one kilogramme the fatal dose is 0'00035 gramme j for a. medium-sized frog 0'00004 gramme. In the ca e of the rabbit dea.th takes place in from ten to fifte n minute .2 ccording to Bahm there exists in orne pecimens of Curare a econd alkaloid, which he has i 0180 ed and caUed curine; it is, he say , much Ie s poisonou than curarin , but in e periment , e pecially on warm-blooded animals, it pre nee may modify the result, as it directly paraly es th heart's action. In u ing curare for any purpose we have olely to depend upon the old extract prepared by avage, and hi i a great ob tacle to the introduction of the rem dint meuical practice. Its composition i v ry unc rtain nd variable, and we do not posse s the lighte t ecuri again t intentional adulteration of it j whil t, when e po d to d mp iI', it rapidly deteriorates nd become inactive. In ] Th. acb, < nn len del' Ohemie,' 1 78, Bd. c ci, 8. 254 i W. Prey r. < 11 em. iener med. Ztg. ' 1879 ·554, , R. B"bm 'Ohemi cbe tudien tiber da Ourare, from he 'B itl'iig zur Phy iologie,' I 87, 8. 173· 12 E PLO E T OF UR RE J TETA olu ion hi chanD" e m 0 take plac till more olution of thi na ur , 17 HYDROPHOBIA. 127 ame charact r in all the e ca e, he effect of which i not weakened by curare, is generated in and ab orbed from the wound, and that too for a considerabl time.1 Curare act in the e and other irritable conditions of the reflex centre, a morphine and chloral do in the continuous in omnia which occur in certain ca es of yphoid fever. In tho e ca e of tetanu in which death occurs in a few da , through exhau tion of the nervou centre, the ran ient depres ion of the motor nerve may alleviate the mptom : Ie s acute case tend of themselves towards recovery. The ubcutaneous injection of curare has proved u eful in aIle iatiuO' the ymptom in everal ca e of hydrophobia in man,~ and once in a ca e of h terical hydrophobia.3 In one of the e case nineteen do e, containing altogether 0·3 gramme (51 grain) of curare, ,ere injected in the cour e of twen y-two hour ,with he following re ult:-"The patient brea hed quietly and became indifferent to draughts of air he trength of which wa purpo el incre ed." Previou 1 here had been con tant excitement, convnl ion on wal10win, e treme dread of water nd of draught of air. (( In he cour e of the for noon he I' pe tedl a k d for brand on account of hi great tbir , nd twic ook orne; fur h r in the afternoon he ucc eded ithou an difficul ,whi1 t tanding, in drinking a cup of coffee." n unfortun t occurrence rendered he continuation of th reatmen apparently impo ible, and the patient diec1 in a condi ion of ild e citemen . In the literature on the ubject man ca es are recorded of e perimen on animal J from which it ha b en con-clud d hat pa m which origin te in he nervou centre nnot barr ed b curare. I hould h ve b en ob i u , for he l' a on b ve given, h t he e pa m can be c n rIled b curare, for it i impo ibIe to under tand how ny im- 1 Thi ha ince b en proved by the e cellent ork of L. Brieg r in Berlin. • F. . Hoffmann Berliner klin. Wochen chr., J8i9• . 637 j • ake, •D ut cb med. ochen chl·.,' 18 0, 8. ,.035 j P ntzoldt, 'B rl. klin. "' ochen cbr. 1 2 . 33. 3 if nb r " beil Hund wut, Bonn 18i9. 128 'fRE T E T F UURARE POlO ING. pul from the nervou centres i to reach the muscle if curare) by actin on he terminal organs) put an obstacle th l' to the further tran mi ion of the impul e. Certain perim nt which I my 1£ be an) nd which one of my pupil continued and publi hed)l have proved that cu-rare is able ev n in animals to arr t the pa m originating in hi way. The e experiment b. ve meanwhile been uper eded by tb result which have been obtained in the human ubj ct. have still to con ider THE TREATME '1' of per ons who have be n poi oned by curare. oderate do e kill simply by paral ing the re piratory movement. e can conequentl av rt thi danger by e tabli hing artificial respira-tion. ir B. Brodie long aO'o gave a practical demon tra-ion of thi.2 He put ome curare into a wound of a mall tom-cat. Tbe animal was paralysed; re piration ceased) but the heart ill continued to beat 104 time a minute. Brodi now plae d the animal in a temperature of about 30° C,) and pumped air into it lung.. The heart continued to b at reO'ularly) the iri wa contracted) saliva and tear were ecret d, but the nimal till remained motionle. rtificial I' pir tion wa continued) and at the end of an hour here ere fe hallow re piratory movements; at the end of noth l' bour pontan ou re piration was e tab1i hed. The nim 1 n lept onndly for forty minutes) then got on its 1 0' nd alk d bout. p tient who ha been trea ed with nt· l' ou bt lw Y 0 b tched, and vel' hing mu be in l' adine for r cheotom ) althouO'h) a far a I know, hi h never et b nne ry. L I' do e of cur r nd ometime mall do e if con-tinu d for a 10nO' im par 1 e not only h rno or nerve, bu he h rt al 0, and p rhap other organ. l' ificia1 l' pire i n yer? hoI' a 'to l' counter. c ing thi . ver me n of imn! ion mu t b u ed) but bether he r u1 ill e uece ful l' not i doubtful. al H ilmit I' ction of Poi on ' • Phil. Trans.: 01. xx viii, p. 17 . HYDROOHLORATE OF OOOAl E. 129 From the earliest times a shrub has been cultivated in Peru, the leaves of which the natives value hiO'hly a all indi pensable luxury, just as other nation value alcohol 01' tobacco. Lamarck, in 1749, named the plant ERYTHROXYLO r COCA; iemann, a pupil of Wohler's, i olated an alkaloid from it in r860, which he named cocaine; and thi alkaloid ha recently b en added to the Ii t of remedie . The officinal form i COC I UM HYDROCHLORICUM, Cocain Hydrochloras, hydrochlorate of cocaine. It con i ts of colourle s, translucent, odourle s, anhydrous crystal, yield-ing neutral olutions with water and with alcohol. Th crystals have a bitter ta te and cau e a temporary 11umbne of the tip of the tongue. 'I he alt ha the empiricial formula C17H21 04.HCl. By heating cocaine with acids or with cau tic baryta in a clo ed te t-tube it i decompo ed, with ab orption of 2 mol. of water, in methyl alcohol, benzoic acid, and a ba ic ub tance, ec onill (C9H15 °3): C17H21 04+ 2HZO=CHs·HO+ C6Hs·COOH+ C9HI5 03' Be ide cocaine the leave contain benzoyl-ecgonine, and nother base, hygrine, neither of which po e ses any medical importance. Cocaine i11u tr te in a remarkable way he 10 pro re , hich is made in our knowledge of the therapeutic value of f miliar ub tance. Thir y-five year ago ohler reported upon it very triking and int re ing property in th follo ing t I'm :1_" It ha a bitter ta te, and ha tbe p culia)' flect upon he nerve of he tongue of making the p iut of ontact temporarily numb, and almo t devoid of eu tion." Thi i a clear t tement of a fact which in our da ."cited he k n t in ere t. In 1879 B. von nr p2 di cover d th< t "ben thi alkaloid i injected ubcutaneou 1 ,th kin become in n ible to he prick of a needle in the neigh10UI'hood of he pot wb re the injection ha be n made, nd that it ha the me effect if it i painted over th onO'ue ; n he therefore recomm nded it a a ( local In 9 1 0 000 1 E. not till he ear I 84 that a thi di covery in pI' ctice.1 ince perim nt have been made with it been employed on man with good o t k place nii th irun(1' COO I E. 131 FIG. 4. Cocai71e. .! in mucous membranes which have been painted with solu-tion of cocaine. arrow passage -for example, the insid of the nose-are thus rendered more accessible to examination, apart from their diminished ensibility. The ensory nerves are paraly ed in their cour e as well a at their terminations. .A large rabbit, lying on it belly, i £ tened to this frame j about 4 cm. (I i inches) of its sciatic nerve are expo ed and a trip of cardboard is placed underneath thi. To the brain. I now come to the experiment. which is depicted here: at H cocaine)) I apply all round the nerve finely powdered cocaine with a drop of water, and then wait a few minu e. If I now stimulate the nerve at the part (( to the brain)) with a very weak induction current, the animal become extremely re tless from pain, and he leg i tetanized from above downward. If I timulate the part at H cocaine," the animal remains quiet even when the current is greatly increa ed, but the foot is te anized as before. The cocaine therefore ha had an inhibitory action upon the ub tance of the en ory nerve-fibre, but ha for the pre ent left he motor fibre unaffected. If, however, we wait a little longer, we hall ee tbat no motor impul e can pa (( cocaine." Finally, To thefoot. if I timulate the porion toward the peripher, the foot b com violen ly t tanized, though here i no indica ion of pin. Thi l' pid par] i, fir t of the en ory and th n of he mo or nerve-fibre , which quickly p es off after h r mo al of the cocaine, i a proper peculiar to cocain lone among all h alk loid with hich we are acquainted. 'rhe other hav preci ely he ame effect as common alt, timulating 11 nerve in both directions in con equ nce of the i hdr wal of moi ure from h ti ue.1 1 The condi ion men ion d re in I 860b er d and d crib d indep nden ly y four ob erv r : H. m • reh. f. Anat. u. Phy iol. Phy iol. btheil. uppl., . .293' J. Finberg 'Berl. klin. oehenschr. ' 1 PH 10LOGIOAL EFjI'E T OF 000 1 E. 133 he do e and method employed in giving th drug. the brain i I' ndered amemic by cocaine, tbe h ad of a per on wbo ha had an overdo e ought to be placed low, and from three to five drop of nitrate of amyl bould be inhaled, a hi effectively e pands the vessel of the brain.1 "'\ hen cocaine is applied directly to the surface of the ey ,care hould be taken to prevent evaporation, otherwise 10 of the epithelium of the cornea very soon take place.2 'fhi 10 s i ue to exce ive evapor tion brought about by defecti e closure of the eyelid, and by dimini hed lachrymal ecre ion, one of the results of the va cular con triction. The o-call d PHYSIOLOGICAL EFFECT of cocaine have still to be discll edt In man, when taken internall ,th drug produces a diminished feeling of hunger and of the nece ity for food, with an increa ed capacity for phy ical e ertion. On account of th e propertie he plant is highl teemed by he outh merican Indinn, who chew the leave . Dimini hed ecretion of urea and of pho phoric acid ba been noticed in animal ; 3 whil t the ugar a al 0 ome-hat dimini hed if they had been previou ly render d diabetic b being fed ith phlorizine. Th action of c caine on the nervou y em of nimal prove h t taken in model' te do e it i at fir t a po erful timulan'" nder its influ nee thermog ne i ,5 the blood-pre nr, nd he number of re pir tion are incre ad j and if h ctivi of th t 0 la tel' hn been dimini hed by me n of chloral h dr te, or an druO' wi h a imilar par 1 inO' ac ion, oc ine 'n re tor i. Large do a can e dea h, primarily b timul ing he ra pira or c n l' ) ther by in nciuO' nu of he I' pir 01' mn cl ,an econdarily by h par ly i of h ner -cen l' which 0110 thi imu} ion. r i y d. 3 I E. of c cine-commencing 00 I E. 13"' pharmaceu ical chemi t. The tabloid ar readily di - Ive in a few drop of water. they contain v ry littl cocain, he are made up ith a little odium chloride or nlph teo Other ctive remedie , . uch as morphine, rycbuin, T ., may a1 0 be obtain d in thi form, '\ hich i not onI convenient, but i one in hich he remedie are not Ii bI to undergo change. II. R rbu L J l' -Pro rt' and 7t e-.J.coll'tin -A glitn}J e 'nto tJ p .'t- 'perim nt.' of J[ tthiolu '1 the i:xt nth C II lry- oi 110tl a t'on- nc da 'n cO'lnpo ition of tlte aem itill of com mere -It cl'nieal appli atioH-~ 'ratrine -It ,tr t. -Int mal and ,t rnal 1£ e-E llebore- 01 h'c on autumnal - po' on and a medi i, e. nd I onl T hen giv ub tn,utially the reference L BELl. 137 al 0 animal 1 ITE. THE EXPERI E T O~' I lTHIOL 0 13 OJ 'F.PE T 0 CO ITE. RIABLE Q,U LITY CO IT!... E. 141 IllV f ion d h COUi hi h I L nd D, I I, 01. i, p. 4i2' reb. 1 ... ITll U E OF ACO ITI E I.: EUR L I • ]4. of aconi ine. Bo h the e re ult ive ri e t be r pira ion, c ano i, nd n ral arm-blooded animal. Th d 0-1' b cau e it f th b induce p ral i I 79 B . 1 iii, of 1 ER 'J' T E. ere tin ure r par d from it are In form r dition 0'0004 gr mme(rh of 145 i chinO' in the 1 n ct i h he c n- 11 more 1 hol. n .. I -6, Bd. . 2-7; v. Bezold urzb. phy iol. Labor, I 69, . I' ic u. 10 1 F ER '1' 1 E. Ot HJO 14·7 d. l' h. f. _p r. p, h. u. Ph· I'lll' k.' 1 9, d. ii, 01 OLCRIOU B ECTI ... ' TO IT U E. 149 rh umatic ca i ue to a pecific ac ion of th col hicUDl, r th edati ffe f th morphin. The p iti harm hich colchicum cau in acute articular rh umati m i: kno, u, nam 1 ,viol nt diarrh Thi comp 1 cut utly t mov hi limb, which n iti ,and hi tr ngth i thu I l' llt ime po.. in odium licylat, antipyrin, an imilar m dicine , r medie gain t rh um i m and ou, ~hich ar ffic ciou in a much hi her d gree than col hicum, nd which, moreov 1', ar £1' e from it irritatin an an-rou. prop rti . III, II yl ?Litril -It' a t 'Oil upon tlL c r In'al 'l;. el. - P01l tit 7)tu/) 7-pr ','W' and hart-It 'l!.' 'n pa rn (1 the , . 1. -~ II !J tl di' d 'antag of tit drug- ?'tific 'al di IV i ,'1>1' dll' d by 't, 11 -J,l1etJ >tnogl{)bin appem' alte?' pI' 1 lit d t' - odium nit?'ite- itro-glyr. rin " 11 ' : ur notic or 0'1'1 .. }<' n ITRITE. 1 1 1 w r h ar runton in I ud I' in ner 1 IDO readil ere i a ealed gl tub of the th r. I bI' ak it in a I'm 1', an a nak d pc· m r lin. d. 1 ;6. d. ii . 12 . 1 1· tion and izzin TI OF IYL .1 ITRITE. ation of the ron 1 j up r ana from th th r ctum-fall litt1 in 1'0 d y the thermom tar.1 of h at £r m E'FFI!}C'l' THE BL OD-PRE URE.A D 0 THE E RT. 1 3 h bod whi h i under th influ nc of amyl nitri ,and h ame tim di id the pinal cord in tb rvical l' .on, we hall th n ee that 11e drug till pI' duce an ffect upon the ve el of that part. Th it ac ion i periph ral and xert d upon he w 11 f he blood- el i upport d by th fac, tha th vapour f amyl nitrit quickly paraly e i olated moo h mu cle n h ontr ctile protopla m of the low l' or ani ms; and, mol' 0 er, if m 1 nitri i j nh 1 dafter clampinO' one f the carotid arteri , it doe not alter in th Ii ht t h calibre of b blood-ve el of th I' on th t id, wherea if the 'ympathetic i cut after the art I' i lamp d, tb y el of the ear, hich previou ly w re colI p ed owing to h clamping, very quickly and di inctl dilat. Filebne hold that he paraly ing ac ion of myl ni rit i, rt d chiefl upon the va o-motor c n re in h medull biongata.1 Thi c ntr ma be act d upon a ell, u tbe paral i m to ,on he contrary, chi fl f a PERI-I'D ERAL character.2 The blood-pI' ure f II at once n inhaling am 1 bu it fall much 1 ,if a all, when in nimal' h pin 1 ord bing divid d and h v el in h trunk and l' miti th l' b dilat d, h abdominal aort imul-t n ou·1 compr d. I follo' fr m thi th th f 11 f h blood-pI' ur no due 0 a e k ning f th h ar ' ction. In human b in r di in 1 1.. l{ h u d n fall f blo d-p il t ti n 0 h bi d-v 'imulu upon tb Thi iroul ti n f hId-pI' 1 o TH HE T ~D E PIR TIO • c ntr ction in-nitri and it of th be b t mol' r pil'ation hich i' pectori J tl A PE '1' Rl • Tracing of normal plll e. TI'acing during he attack. 1 - u evere pain in the cardiac region. Pain temporarily reli v d by th u of YL ITRITE. Pain compl t ly r li v d by lYL ITRITE. uder Brun n, r prin from th •R or nd n, I 70. EPILEP hich w r n or- 1" in tl'U • D GEH THE U F 1 L TrRITE. n £1' - ca , d ill 1 ni rit h £01' hr" l'. <Z i chI', f. P ychia ri ' I" Bd. ii .527. B FE T F lYL 'I'l'lUTB 0 THE D orne ime, th r joan, ho - Pharm k I. AOTIO }' ITRITE. 1 9 1 '0 ODIU ITRIT '. ron ni c nd , and the expo ed ciatic n r (', n r 11 ,10 their electrical excit - previou 1 to th ould h v r tam d h other ide j the blood, and rium- ODIUM IT 1'l'E. 161 11 1 oJ B. ITRO- L OERI E. 16: .gJ riup n 111 r in (tran 1. . Iodiue- onn )"Zy 'U ed "n '1ned" in a E. TE L D 1 TER L TIO OF 10DI E vn £ 1 ~.. ERI E T pl ..}".,~ ...,,\;)·' reb. f. . II i. t • EXPL ~ TIO OF 'mE TI o· I DI r.I!l ITER LLY. 167 red m f th 1, r lobe f th r ,a in th lain d on a , The i to and rum i not-a ha b en Iu ion i pI' dilut al n 1 F FREE IODI E. OTIO... OF I DJ E ~ T E KI • 1 9 • JOl. '11 '1" HI U , 17 I DJ Cl!:"T '1'r UE. found i din in th urin EJ!FE T 0 ADJ El:~rr tIl U 171 172 IODOFOR.1!. 13-mu t ben id r d ne di to £r i din r ion, it ntain 96.7 =I,3xI= Ij hi m le£ iodo orm lcohol, t hi h IF. ~lin" 'l1l un • ell).llhI. f. bir.,' 1 ~o. 2. I TRODUOTlO A A RE lED • 173 4I~ + ~H5.HO + 6 aH = 5H~O + HIs· aI + hr. f. D rm 01. u. n 11 t ED B ·AT D IL. f w un 1 an ulcer I nd will di· l'T £ I'm, whi hi h n e ompo d and £1' in a , l' of "hit 1 iti n. which re Ho EFFE ·T. PROD l:D B 1 DO P~r. ] 7'" n b which iod form i o of n fund In f: 1'110 '1' 1 . 1. 17 EFFECT PROD D B lODOFOR . na cent hydrog n, 2 HI3+3H = 6HI+ 2 2' iii . II2. . 7 und EXPERI E T 0 AL • 177 h liv r, m If, n e lanation or ptomaln ex- 12 17 1 'fER r L D 11 11 'fR 'rIO F IODOFOR 1. fiue u m mbrc n f h lat r i pal and wrinkl 1; £ he £ rm r i r d, ~oll n, nd", h n dra nu, Thi diff r nee i r mark d· w hav a norm 1, in th 0 h r an infl m d mueou.. or i D I 2, ITER AL D~n I TRATIO OF IOD FOR • 17 or th iodine lU he c n ha produe d u h '. I 'I'ER L OF IODOFOR • °th ulphuric acid in the organi m to < id, indol- ulph nic acid, co, the ." I' d in h urin. Th amoun of m a ure of the moun of putI' on in th inte tin. en to a do i greatly dimini hed IODOL-POTA IU IODIDE. 181 the iodide and iodate. It now appear to b abli h th t b giving e eral do e of one gr mme (15 gr in ) of odium bicarbonate, we c n alleviate he ymptom and 1 n he effect of iodoform poi oning. Th mell of iodoform i very much di liked by many p pI, nd con equently anoth l' organic compound of iodine i omtime u ed, namely 10DoL. Thi i prepar d from iodin nd p 1'1'01, the latter being one of the product of the dr diillation of nitrogenou compound ; it formula i C4H4• lodol i 414 H, or t tra-iodopyrrol. It i a Ii ht ellow, dour! powder, hardly oluble in water, readily in alcohol, and till more 0 in ether, and contain 8'97 per cent. f iodine; oil di 01 e about 6 per cent. of it. "' hen applied to animal ti ue it i ab orbed; at lea ,i a t a an anti-eptic, and appear a a oluble compound of iodine in the urine. lodol wa fir t de cribed by the chemi t iamician an ilber, in ome, in January, 18 5, and it wa pl'. crib d here by azzoni.1 inc hat tim i ha oft n b n ed in t ad of iodoform. I i no, ho vel', innocuou, . a ho n in a ca e here 5 gramme (75 rain') prinkl d er a ound cau ed re tle ne and d lirium, follo d in e ibility.2 ochen cbr.,' I .. , . 695. un I 6,.694' heften, I 8] p. 324. DEOO PO ITI OF POT IU I DIDE I THE Y TR 1. Iu ion, i din i t fr , ivinO'to h 11 , ,an if chI rof I'm i add d, a viole colour' cid to h olu ion of pota ium iodid a of pot ium bi ar rat i formed n . h fr h driodic cid, hu +H .0 06=K.H.04H40 6+HI. ta ium iodid i prepared on alar e cale-amon t h I' m thod -b mixing iodine wi h a omewhat conn rat d lution of cau ic pota h, and then ently heatincr iodin no 10nO' I' di colour he olution: 6 OH +31, = 3H20 + 5 I + KIOs. Thi i evaporat 0 dr ne ,and in order to reduce the pot ..iu iodat which-a ppear from h formuIa-i al 0 form d th I' idu i m d with charc al and fu ed in a I' d-h t iron crucibl, hen the followin I' action take place: 6 ium iodat , which 1. f I' albumen IODI E LIBER TED FROM IT BY LIVI G PROTOPLA M. 1 3 nd 0 her con tituent of the human body, it i difficult to e plain how the beneficial effect which l' ult from it u e ari e. I therefore ought for "om vidence hat condition mi ht po ibly occur in the body by hich h iodine of thi chemically inactive salt might at time be liberated," 1 and found it by applying and u iIi ing a fact no iced by chonbein, viz. that certain part of plant, when onnd with water and acidulated, decompo e pota ium iodide almo t imme<1iately. It wa not known what the active agent in this decompo-ition wa , but a the re ult of further experiment I howedt that it wa he PROTOPI..ASM which wa lib rated from the cell-wall of the plant. Thi impart activi to th 0 gen of the air, and the ame re ult occur hen very m 11 quan itie of na cent or active oxygen act upon an acidulat d olution of pota ium iodide. If we u e carbonic acid a an cidifying a ent, e have the arne condition a eri t in th human i ue. The imple experiment may be made a follow : fre h leaf of Lactuca ativa., which i vel' rich in protopla m, i ground in a mortar tog ther wi h a few cubic cen ime re of water j a I p l' cen. olu ion of pota ium iodid -or better, odium iodid -i a urated with rbonic a id at a temperature of 150 • (590 F.), a Ii I mucila of tarch i added, and he mi ure divid d into par. I add to the one half ome of th pro opla m nd wat 1', which ha a neu ral reac in' to th oth 1', h . m quantit of ordinary water. The lat l' l' main undecompo d v n wh n it ha tood for a I ng tim. In h form l' a ou ,h blue color tion b n 0 app ar in f minu ,indica in th lib ra ion i din , and i h n rapidl and full d v lop d. Jut a arbonic a id b it ]f cannot lib r t o nih l' an he pro opla m do 0 unl h acid i al pI' a ur 11 thi do no hoI 0 d fran ind fini olu i n f pot ium iodid will du 11 . inz' Die Zerl un~ de Jodkalium im 0 .. ani mu " f. pa b. na.' 1 75 Bd. lxii, . 124; , r'b. f. xp r. Ph rm- k.' 1 94. Bd. xiv . 185. : '. Binz 'Arch. f. p tho na. ' I 69, d. xlvi, - 145. 1 PRODUOED B POTA IUM IODIDE. compo e under the influence of light, air, and orO'anic t r. If I H hoI r nt , in our r gi\ n b KI + H °+ 02 = H Os -t- HI, 2 I + °= H20 + I , EFFECT PRODUCED BY POT IODIDE. 18" 10 in nd 1 EFFE T PROD OED BY POT 1U IODIDE. h. Banml r . lOI. IODI 1 h. it been reported to ha e occurI' d und l' n I : ium iodid for con-ff c j 1 h JODI' • 11 he than a hen th nt, acute dema of he iii, . II I. JODI M. the e cutaneou eruption 1 odium or 11' 190 rm.l human aliv 1 DI MODE F.E RET! (4 0 ain), and hi 1 1 r 1 :. 'l'R TIO 0 POT IU IODIDE. hakiuO' hi he b orp-ii Iodidi (' Ph. Bri.') on i of 16 p h ODI M I DIDJ1:. n nl ium i did and I of l' and mi d 'ith lIO at' 1 lin 1 ha a in 0·6 n cau e mor 1 ODIU IODIDE. Erperimental fact bearing upon the production of areo arcotic' cau e opale cence or cloudine in fre h eti 11 of the brain-Role ofthe halogen in thei1'cornpound -Gontraction of the blood- e ,el in the bra 'n-Lot ering of the blood-pre wre - Atropine - t'muZation of the bra 'nAncient and mode1'n tatentent -Gene1'al d C1'l'pt 'on of it poi onous e.ttect -Paralysi of the periphe1'al nerv . -E periment 1~pon the ca1,diac branch of the vagu -D'Zalation of the pupil-U, e in therapeutic -Atropin a1 d u ca'rille-At1'opille a apoi on-The1'ap ulic antagolli 1/1, b~tw en Morph'ne and Atropine-Hyo cyamine and Hyo,etne. emplo d a' HI03+ SHI=3H20 +312' hether, nd how f r, hi proper of mor- , he cell of the br in canno a b 1 OTIO OF ORPHI E 0 THE OEREBR L ELL. The following micro copical chang ith which e are immediatel con-been bled to death by opening the ith a in ·31' fr ipr""p ril't 9· 01'10 OF MORPHI E 0 THE OEREBR L ELL. 1 7 cerebral cortex j the officinal neutr I al of I' chnine nd uinin act in he arne manner a morphin 1 The opal cence or clouding of the fre hI prep l' d br in c 11 i e t1'emely di inct, and i at once i ibl i h n me O'nif ing power if they have been expo ed 0 he v ponr of chI roform, or treated with a neutral olu i n f chI l' 1 h dra e instead of morphine. The e change ar d pic d in the accompan ing illn trations. FIG. 6. FIG. 7. The hole proce necro i , appear 19 I P RTA TOE O}' THE H LOGE •. .l. DITIO OF THE CEREBR L "\]) EL DURI LE P. 1 cion t 11 upon m ,va. lrat in 1- ad fini ODIU LUO IDE. 201 TR PI PI 20 • 'fHt: PEIIP L ER B ~ ERI 7 tTl 10 p OJi E ETORY 2 hi 11 f HE UTI E THE.R P TI H O' T OPI 211 th THE PE TIC o T OPI FIG.S. FIG. 9. 21 1 TROP} D J1I. ~J O\.llAn T PL. E J: D to e t. m nt, FIG. I I. _1 GO I A D T PI 1:.. 21 our to limin t combin i h i D T Ph E. TR I E. _..1 Hl E PI 22!'" :.. TR L.~E. r, n rco i nn coll p bu HO '1 OPI 227 u d in oph halmic ur er , 11y in ho e c , h l' i iDee ary to dilat the pupil £01' dia no ic It loc I nodyne ff ct is id to be much gre t r of atropine.l Th ma imum dose and the maximum qu mini t red internally during he day, are th of a ropine. The £ollowinO' formuloo pre clearly the r 1 tion hip betwe n homatropine and atropine: 017 28 03+ 20=09 10°3+ 0 15 o. tropine. utero Tropic cid. Tropine. o 15 0+ Tropine. 1 Filehn , • B r1. lin. och chr.,· I 7. o. 7. 1. ct 'on 01 ct 'o-n 01 an the araal o EI'. moi tened ith a. olntion of mmoni nnio t caff in from an queon olution, bu l' TIT I . 12. I . I • (I I 111 fll.IHllmlJr"."/.f" WI "".ill'II./I'" II Fr .14. J u' r 2 r . J::. .. 7 E. THE ULTU F .. 1 D- 1 . 17. H I . I I • O. I . 1. IPL II Tn T. aTI f Tn IT LI . POI 2 ROP TH R T. p T. TI t. _ 1 II. _I D 7 TI L: 0 TI 4 OF 2 .:-v,,,,.",I.•.n.Il .•. OL G.26. T TI L. II H. H. .. I Tvu... v ....'v r I . 01 LT . TH' R' LT. .. IJTB - I D ID L. TI ... 0 ID L. o 30 1 IT ruein 11 11 3 p T[ 4. T • 31 ammonium in 10 h purifi 1 n 1 · 1 111 TOR ~ ETR L A II t. 1 20 TI wih Ob' .\L H L. t r, f I' h eel' ion weI' then man OT10 OF LOOH L. 321 h 'olone of ir r .pir d urill!l t n minut. (, iimated in 1itr ,), Percent. e 1D rea e in the rond column. '7 6'7 9'0 6', 9'0 9'0 ,-I 6'0 9'0 7 1 0 hinin und ho a er alco 01. (tu t D mlnu e . 3 2 I FLUE OE OF L OR L PO DIGE 'TIO • 323 50 r he chr., 1 9 , iol.,' 1891, Bd. xlix ACTIO OF ALCOHOL 0 THE KID E :: Zun In. , Bd... 2 FFE T F LO HOL 0 THE TE PER T RE. EFFEOT OF LOOHOL 0 THE TE PER TURE. 2- FIG. 2 • ••0 F. 9 F. 32 E FEOT 0] LCOHOL 0 THE TE PER TURE. ion on a. h lthy m n, i hteen th 0 h ]jJ ORETlO OF LOOHOL. 327 ~hich gave diff rent re ult ,nor a ub equent Engli h r fu tion, t nor the more recent in e i atio of m pupil, ere ble 0 di. place it. xact and u horitati e in iga-tion of thi ubject therefore nece ar . inve i a ion of thi kind a carried out in m 1 bora ory 2 in I 83, which, be id howing the ourc f 1'1'01' of th Fr nch in e ig tor , cle rly demon tr t d h f llo in fact : hen model' te do of alcohol ere tak n, h great r par of it a excreted by he kidne and the Iun , very mall qu n i y by the kin, but none by th bo el. Ito-h l' about 3 per cent. of it wa reco er d from h al hy a uIt j in dogs 0·6 per cen . more wa obtain d. Thu : In do •. In men. xerelol'} 0 ,'umber of Percen e PerteD e quanti e perimen excret Iexp.n~b"e otar. :~lid. Kidn y 4 1'576 12 l"ln kin 2 3 0'140 Lun 3 1'946 3 I' 9 ---- --- -~I 3'5 22 2'91 TRITl\E L E F LC BOL. UT&T'l'l E AL E OF LOOHOL. 32 330 In i d EDI I L EFFECT OF ALCOHOL. at ment of L. Rie ,lone of hi ubj ct. To heal hy man, , were given o 160 .c. of diluted alcohol, hilst another, , to 3...0 C.c. The chief con tituent of the following r nIt : Per ntage of the Da'Zy Decrea e. r • In hirteen r ric id. 1 I ric cid. 16 ulphmic acid. Pho pboric acid. 22 34 ulphuric acid. Phosphoric acid. 2 II EDlcr AL EFFEOT 01<' ALCOHOL. 331 rei e e treme e u ion in the admini r tion of t m eh 3 .. F ECT 0 'r E E RETIO ~ OF ILK. alcohol ill i, .;. TIP RETIO FFEOT F L HOt. 33 A TI • 01' L OHOL I - F. TTO FEYER. FI .29. ACTIO OF L OHOL HE Tl he fir t rl f d TIP RETIC FFEOT OF L OHOL. A TIPYRE'l'IO EFFEOT OF LOOH L. 3 7 th TH RD T PIRIT. IE. 339 ~c., \ h n H In "h be 11 BEER. 41 f L OHOLI h nic bri fl . clinical L OHOLI •• i not 00 pro OHRO 10 L OnOLI !!lOO DARY PRODUOT 0 DI TILL TIO • 3 r. P h. u. h rm . 1 F I IPURE L OH LTC BE ER GE POlO OUS PROPERTIE OF THE OLLAT R L PRODUC'f • 317 POI OF YL LCOHOL. 1. The ethereal or e ential oil -Their o'rigin, propt:rt' , cla i. lication, compo it 'on-Oantphor-Ea:-p rim nt upon human be 'ny and warm-blooded animals-Anti ept' prop rt 'e Ant 'pyreti a tion of camphor- timu,lat 'on of the h rt and r piration- cretion of aliva 01 d P ,. 'P'ration- Prep rat' 11, - amphoric a id-Turpent 'ne - TI rpin hydrate- dati 'e a tiO? of the ether al oiL UpOl t} ner OU y tnt-The Phornw.cop ial pr parat 'on if tl th r al oil 0 lId oth r allied drug', THE ETHERE LOlL . THE ETHERE LOlL. 351 3 - C PHOR. EXPERI IE T 0 nu BEl G • o W R -BLO DED A I AL•• A "1'1 ~P'l'l PR PER'1'lE' F oc ur e n wh n th obIon ata, provid d 1 Pil PRO. I - •. 2-. TIO OF C PHOR I ERY IPEL ACTIO OF 0 IPHOR I FIG. 30. EPTIC FE ER • 35 PH R TH H T. ACTIO 0 THE KI D UCOU 59 he ac ivi y of he 60 PH R1 OlD. OHEWOAL PROPERTIE OF OlL OF T RPE.. TI 61 of h A TI EPTIO ACTIO OF TURPE TIrE. 363 em nt to e, nd i d to 30 gr mme of oil of urpen ine h. 36 THHR PE o IL 0 TURPE TI E. THERAPEU'fIO EFFEOT OF OIL OF TURPE.l TI E. 36 hich 10 .o.u".UU.I'''.' ull. n. d b from c mphor b be n 0 rna b pre crib 3 E ~TE I 'IRE RI TE. ther ca in b oil of a imilar TERPJ E H "DR Th. ing ublime a fine ne dIe ; he di 01ve in 2 So r of cold water or 10 part of alcohol. Terpine hydrate i oil of turpen in wi h he dition of three molecule of water. It i formed when the oil i lef in contact with water for a long ime, but i n uall prepared by reating oil of turpentine i h alcohol nd a Ii Ie nitric acid. It i employ d for the ame purpo he oil, but e peciall for chronic bronchi i j and po e e he advantage of being fr e from the mell of urpentin, hich many people i ver di agreeable. Terpine h dr when taken for orne time, give ri e 0 no nnpl ptom be ond orne di urbane of h j(7e ti func ion, which rna alw be obviat d b takincr h d·u on an empt omach. It do e i 0"2 0 o·S (3 0 7~ O"ram) dmini t red 0 or hree ime d . L'pine a he fir t 0 introduc rpine h r in 0 prac ic . 3 OIL OF p on - rucin LERI c a w r moun In ei ht 0 mm. ED TI E AOTIO 0 TET I ED A I AL • 369 they recur, but only in the hind e remiti hen he animal i pushed. . as before. 120 min.-A. is now quite fr e from pa m, and rem in quiet in a corner. Both animal completely reco r d. ill con i . co 10 0 h r-i Th OIL Oll' VALERIAN is not the only ethereal oil hich po e es this striking property; I found tha the OIL 0 L, CH 0 ILE, UCALYPTU, and TURP TI 801 0 po d i. Other have repeated my e perimen , nd h dd d OIL OF PEPPER I T, &c., to the Ii t. Here are the detail of an experiment ith oil of urpentine: T 0 young rabbit -T.= 520 grammes, .=530 r mm 9.45.-'r., subcutaneou injection of 0'25 ramme 1. T r b. in an equal quan ity of oil of eet Imond. IO.5.-Bo h I mg. brucine. 10.30.-B. run about r tIe ly; T. i quie. IO.45.-T., a ubcutan on inj ction of 0'25 gr mm 1. T reb. a before. 10.45.- 0 h 2'5 m . brucin in he cour of mm I I.42.-T., 0'5 gr mme 01. T r bin hin . I 1.43.- ., iol n attack of con ul ion . J I.46.-T. in th arne condition b fore. I I. 5.-B., iol n ck of convul ion, in 12.-T. Ii qui 1 on ill. R P hen pu h Thi follo y f Ii h hind 1 12.10.- o D TI TIO 0 THE E OUS TE • 3.55.- a orne Ther en or pre en of brucin. no d en THER PEUTIC E fPLOY IE.. T OF OIL OF TURPE TI E. 71 ue. , are from in, oil in he 37 th OIL 0 OR [Q ILE. goni ill to tho e cont in a. dark Blood·pr ur. 110-1 5 mm. Tim • 1 I .... 1 .1 1 . 0 I. 0 il inj ct 110-11 o 6 ..- " " E THOL. 373 fir t to men ion the effect of peppermint in lle ia.ting pain. In our time it ha again come into prominence.1 The <>fficinal oil is given in do e of 2 to 6 drop , or men hoI i rubbed on the kin over the painful branch of he rigemin 1 nerve. The latter method a introduced from hin nd .Japan, where it h been practi ed for e. The application of menthol produce a en ation of cold. The cold, he contraction of the ve el, and the penetration of he volatile camphor through the kin to the endin of he ffected nerve, m y ver often produce the favourable re ul which have been attributed to the remedy. Oil of peppermin has the ame depre ant ction on he nervou centre of animals a the oil u d b 1'i 801' n ill elf in our experiment. It c n be aken in 1 rge do e , and, like he other oil ,doe not ac on he he r, or 11 vents not at fir t. In the cour e of the la fe e r menthol ha tabli hed it elf in medical pI' ctice, mor par icularly a a edati and dimini hin reBe c ion.2 I 1 y P rticular tre on it beneficial ac ion in the con inu d vomi ing of pregn ncy. The do e i bou 0'05 r mm (of drop) hourly, di 01 d in lcohol nd r 1 rg ly di]u ed with er. It ac iOD, ho, ever, em 0 be un-hu de crib d;- olourle of f 37 ( H CHs V o H..OU~CH.OH H C OH2 OH I sH7 en hoI lOH..oO). e n the 0 i Borneo camphor, from the ood of Dryobalanop in Borneo nd uma r (e ·ugh m r STAR-A E. 37 01. 376 RO ATI The drug, after it has B I THE. 377 Jugla1 reb. de Phy ioL 1 8~, known that oil of wormwood has the same eff ct as camphor upon the nervou cen res. This had already been ob erved orne ears ago by the medical attendant 1 of a man who had wallowed 15 gramme (about 4 drachms) of oil of wormwood. Convul ion of the face and limb , 10 of consciousnes , and violent con triction of the throat were induced within a few minute after he oil had been taken. Complete recovery took place, but, a i he co. e with most epileptic eizures, the man had no recollec ion a to how the attack began. agnan gave a dog of 14 kilo . w igbt, 5 ramme of oil of wormwood by the mouth; in half an hour the animal had an "attaque d';'pilepsie," ten minutes after ard another upervened, and later on the dog di inc ly uffered from hallucination, and ttacked a bare white all, eviden ly takin~ it to be a ferociou enemy. econd experiment f be ame nature i fully de cribed by nan. y own xperimen i h a ropine, pre iou I referred to, h ve repe edly convinced me hat genuine h llucina ion of thi kind do occur in dog . o further explana ion i needed of he fac, h a ub tance bich timul te the br in 0 m rkedl hould-hen t ken in c d y af er d - et up b d gree uch ch n e in he ell, he e I, and he membrane of be br in, a ould I 0 h t form of delirium tr m n hich i ccomp nie by ch rae eri ic pileptic eizure. Tbe imple mu cuI I' remor of delirium remen i changed in he co. e of he ab inthe drinker in 0 n epilep ic fit, hich recur from time 0 time. be fit ce e if he h bi i ercome durin he earl a ; if he indul inu d here i p rmanent er n em n of h in ell c , n ing in par 1 i and de h. he morbid cb n ccording 0 he l' di po i ion of be indi idu 1. l' ome ime more like b ric 1 ac, in 0 f I' hat eripb 1'801 n th i t and con cion ne be re· ined during h OLI J GLA n I hI. f. Jilin. 01. P·3 99- 1 mi b ' 1 62 01. ii, p. 619- 37 o BEB • • • 11 I. h J b bu h,' r OUBEB • 37~ 3 0 cutaneou B L OF COPAI A. copa ifer J found in COP IV It i a. nd ha n B L OF PERU. 3 1 1 • Brudi' reh. f. lin. . • I diure icI_a fact du 0 1 Imu- 1 am which ic ut x, .511. 3' B L OF PERU. o U. I; BAL 1 OF PERU. 3 3 rm • 17; . chul z , 3 B L OF TOLU. an obt ined I a af er hardened F<ETID • 385 J 9, Bd. ii RO 1 TI PREP R TIO •• with water. In the preparation of tenth p rt of lcohol i added to h .E THlE-the finel mn lU.K. 3 7 omitted without prejudicing herapeu ie.; he reten ion of them merely how how troDO'l we clinO' 0 anClen en tom. 3 8 Th K. cont nt of the sc con i of what oft m of a. peculiar, nd per i tent odour, which i minu e quantity of he fU K. 3 9 ramme trong p I' of . I'd addinO' b g-iv D in pouch, and it i carried on by the intermediate agent. 1'he fact that nothing is known about its active ingredient is a econd drawback to the therapeutic u e of mu k. The ubtances contained in he mu k ac are tho e usually found in sebaceouS' follicles-fatty matter, albuminous bodies, oap,. chole terine, traces of butyric acid and lactic acid, unknown extractive, and the well-known salt of blood· serum. The ac contain, in addition, like the follicles of the external sexual organ of most warm-blooded animal , certain odorou bodie, which in this ca e are more strongly developed than usnal. The odour of dried musk i faint, but becomes more and mol' perc ptible heu it i moi tened: the odour 'eern , herefore, to be continually generated in he mu k. cid' and acid alt hinder it development. have no further kno ledg of it nature, nd know e n]e bout it pharrnacodyn mic importance. Th re ha been a natul' 1 endenc to 8 cribe the ac ion of thi drug, a well th t of he ethere 1 oil ,to be odoriferou ub tance, on no bett l' round, hm ever, than on of nalogy. lu k i pre cri d in do of n:om 0'05 to 0'5 ( to 7! grai u ). I '1'1 TURE i officinal. It ha odour of be drug, nd i pI' P red by infu in mu k in n -fiv part of water, and aft r he am quanti of rec i6 d piri. It rna do e of 5 to 25 drop nd up' ard . B THOLO 2
Object Description
Title | Lectures on Pharmacology for Practitioners and Students |
Purdue Identification Number | PSYC000031 |
Description | Includes chapters that discuss anesthetics, hypnotics, antiseptics, and other substances. Digitalis, atropine, curare, cannabis, cocaine and morphine are discussed in detail. Volume II, 1897. |
Creators | Binz, Carl |
Subjects (MeSH) | Pharmacology |
Genre (MeSH) | Periodicals |
Repository | Purdue University Libraries, Karnes Archives and Special Collections |
Date of Original | 1897 |
Collection | Psychoactive Substances Collection |
Language | eng |
Type | text |
Format | jp2 |
Digitization Information | Original scanned at 400 ppi on a Fujitsu fi5650c scanner using Scandall21 software with bitonal color depth. Display images generated in Contentdm as JP2000s; file format for archival copy is uncompressed TIF format. |
Date Digitized | 2011-10-26 |
Description
Title | Lectures on Pharmacology for Practitioners and Students |
Transcript |
LECTURE
o
COLOG
p
:FOR
BY
~z
T T.
oaD. ,aor 0& A. J) Gill tv.
.." I1TIlT
PIlAaM COL IC~L
T LATED FRO 1 THE E 0 D GER.
BY
EDITIO
RTH '. L TH .B.O ..OA TAB.,
I.. DCLl rJ' TR ,. LLI, 0 LLO 1. Til 1l,'1\ & ITt 01' \) 1'01D.
I.
TH
1 5.
H lET
TR L TO PREF E.
f
ho h
The
Lo DO..' 01: mb Y, I 95.
cond erman i ion 0 1'0-
new ern ion.
n dd , nd
1'0£ or inz,
b proof hee .
IV h vie and
m ke lit ral
o doin he h not
AUTHOR' PREF CE
/p1)
ECO C EDITIO
0,,4+the fol1owin page I have endeavonred to pre ent, IV :.~:r a po ihle in a practical form, .. complete accoont of
our pharmacologic 1 kno led e. The chapter do not corre
pond altogether with he individual lectures, but with thi
c ption, he book i 0 all intents and purpo e a repro-duction,
in bo h forID an ub ance, of a cour e of lecture
and d monstr tion hich ex end over two erne tel' .
t i not int nded th t thi hould b a text-book of
pecial Therapeutic, though referenc ha been made to
variou di ea e and b ir l' atment. Oa e w re elected
for hi purpo e which pre ented man of be condi ion of
cientific xperiment; uch ca e 801' often much mol'
in ruc ive than a number of xperiment on animal.
I h e avoi~ d t icological detail, heth r they refer
o n I -di co r d poi on ,or 0 he eft ct of well.known
poi on , or drug , on par icular organ ,unle the d tails
ha om p cial ignific nc or he m ical id of ph 1'-
macolo I have 1 0 avoide ny di cu ion on fac or
h orie hich ere not likel 0 be intere ting to the
m jori y of m uden or r dr.
he quo ions from the ~ ri in of 0 her re, with fev
c pion , tak n from h ori inal work ; by mean of them
vi UTHOR' PREF E.
refer nce can readily b made to any other important
tr ati e upon the ubjec.
On of my critic has remarked that these lectures show
h t pharmacology i more intere tin than many phy icians
and u ent im' gin. I hope hi may till be aid of the
new dition, I hou h in man place he text has been conid
rabl bri rr d. ew edi ion u ually tend to be larger
han ormer one ; but I h hought i de irable to take
an oppo it cur. e nd hay conden ed rather than amplified
my materi 1. uffici nt new mat er ha, however, been
ad e 0 ju tify h claim ha, in thi edition, the work
h b en bo h impro d and nlarged.
h en r I principle ~ hich have guided me in reating
he ubj of pharmacolo ill be found In th conclud-in
chap r of th, e on olume.
C. BI Z.
CD P.
CO T T o OLe 1.
P GE
LO E TIll OIL
b
6
20
47
7499
136
1 0
164
195
228
261
275
299
316
349
OLOG
1.
The ope ofPhal'ma ology-Dio oride theftr t to rite a treat'
on 't- )l, 'ng of h nn kon-Phal'ma y-Pharmacog11.0
y-D~tferent languag 1 ed-Phar/l acodynam 'c TJ
e Pharma op iM- harmacology the 'Ino t a1 cient
ort 'on of the h al'ng art, nd the one mo t freque'ntly
mploy d-The '111,0 t'recent '11, it c' nt( pplication,
i libri qninqu, f om-
hn: L ipzi ,I 29-30,
1
(H In
H•.r OL
po hec r
in on hi
cont in
1
bu in
3
H R OLOG.
no
PH R ACOLOG • 5
ician doe
ll.
ET R.
In I 47 the Europe n ... orl wa
m rke manner b report from
continuou
c ul
hich n
7
ER.
i riol to
a
r
CTIO O.E ETH R 0
contI' ction m h cor-m
n
(( The
D RTO DI 0 ER •
E E T' 0 THE UL R TE D TE P A'ru E. 11
ry 0 long
.161.
1 75
1 EPE TED ETHERIZ TIO •
P D TIO OF LO AL TH I. 13
to
rue ion of m he
e tination in the eeonom , it i el r from
in he
n une
F 'TH R ttY.
TI
ondi ion £ he
E }.ECT L. LL • I!: • 1"'
o
'f b. f. r.
TH R TD IT POUR.
her, 0 void pot here important
pIe, in he I'm, where dir ct irl'ita-h
r 11 in e eral c produced
ACE'L'I ETHER. 17
bo h of hich are developed in e her b keeping i . f
e h I' i pour d upon filtering p pel and then no N d to
v pora e, no odour houl r m in ( b ence of deriva ive of
fu eloil). f 5 C.c. of eth I' re vapori ed, the re ul ing moist
apour mu not redden blue litmu -p per (ab ence of
ulphuri, ulphurou nd acetic cid). £ e her i poured
o er c u tic po h no ello int mu t b apparen ithin
h If an hour ( b ence of ldeh de nd vin 1 alcohol). f
h r i r p atedl haken ith olu ion o£ pot ium
iodi nd e po ed a unligh £01' an hour, no llow
haul b no ice ble (pero ide of h dro n). ther
pre r d in th dark in a cool place in bro nI
bo Ie filled a the top, for Ii h nd ir d com-
2
ETHER.
In he retor .
.0
oh.
nd
I •
1.-0
11·-7
t . 0
penm n.
,. r e ,moun 0 r
in pir d III 1 nllnu e.
640 c.cm.
290 C.cm.
... . m.
i - . m.
ITROU ETHER. 19
Ii!.
III.
HE I L PROP TIE OF OHLORO OR • 21
ble number of liquids of an etherial nature withou ob a.inin
any good re ult , until t 180 t he tried chloroform, a mall
quanti of hich h d been given to him by Thoma raham,
he di tin ui hed chemi .1
Chloro orm i a limpid colourle liquid of n greeable
h ri 1odour and w et ta e. Di, olve in about 110 P rt
of er, nd in all propor ion in alcohol, ether and fatty
oil. oilin point 600 to 610 C. (1400- 141 • 0 .). pecific
1.502 (1·497-Ph. .). It wa di covered in 1 31 by
Li bi t ie en, a a product of the decompo i ion of
chlor 1 by cau tic pot h j nd imultaneou 1 by oub iran
Pari re u]t of the di illation of a olu ion of chlori-nat
d lim nd Icoho1. In 1 34 oma determin d th com-o
i ion f chloroform, nd it i nam. r rded
i richlorid £ form 1 ( )-£1' m formic acid- 1 W
hich i no Ion er p d, hon h h rm i ill u d.
I i c lIed trichlor--m tZ ne bec u e i c n be d rived
h or m h n C ne molecnle of hi . h
1 cnl of chlorine ive h drochloric cid nd chlo-
+3 ] =3 Is·
ction of c u ic po a h,
o pot h ccording to
o HLORO R •
o THE TE PER TURE.
chloro-ho
n b
ening of
E E TORE PIa TIO •
h r no IODO'er
25
L L1 E E F HL RO "0
LOC LI ED EFFECT 0 CHLORO OR • 27
or an endency th reto, he
DO PROD OED?
HO I ROO I PR DUG D. 29
r d corpu cl s to be acted upon, and place hem
bell- 1a which contain a piece of ponge moi tfew
minu e he cr tur are
mall an amount of chloroform
t
n, he
e open
ouch.
. of
p D?
n on per onal u -
DETEOTIO OF OHLOROFOR I THE n DILY FL ID • 31
ni r of ilver. Thi
b ioed from the 'pir air,
ED OR LtEPE TED I H L TIO
i quiekl eeompo ed
rhonie nd h dl'oehloric
1+
-light
deeompo e
ufioe ing
1.
•.:
(c rbon 1
mm ion of
Tl!J T OR THE PURIT OF ffLOR FOR • 33
III
pr
ma here, how-
3
R •
ETHYL OHLORIDE. 35
o chloroform
by
o
qu 1
r . m ch n hr.' I 0.14·
TH ·L BI IDE.
hoI
ETHYL BROMIDE. 37
3
I
11
ITRO o 'IDE G 39
I
nitre
hi h i
water:
compo ition, nd in 1799 found ou it in oxi-perim
nting upon him elf, i rou oxide
odour and e ti h ta t ,i h vier han
(1'527), and i. mol' olubl in t I' th n
20. On method of pre-m
rIC oxide ga b m an of zinc
•
2
mmoDlum
170° .,' nd
,Tid O'a and
zO.
TIlUm
III i
p 1 "'H LI ITR U IDE
EXPERI E IT 41
car ful analy i of the ymptom accompanying hi
narco i how that it run the am our e a j th ca e
under chloroform or ther. Th cOl,tic 1 ub t nc of th
bI' in i h fir t part of he nervou em to b affected,
nd it i affect d more tronal than the other part . e t
foll w the pinal cord, the m dulla oblongata, and th n the
he r. The cornea appear to b unaffec d for orne time,
a ,hen touch d i r pond -by he clo ing of th yelid-
v n aft I' con ciou ne and the po I' to ill have
vani h d. itl! he di ppearance of the n rco i th organ
l' cov l' heir functional activity in the rver e or r.
ngli h committee, appoint d for the pm'po e of
1'minina h l' Ia ive ime occupied by the ariou t
lD h proce , examin d 13 0 ca e. The folIo in ar
1'a at bich he arriv
rom 63 0 cond 1'e r uir d to produc anre-he
i ; he n Ia t d from 22 to 2 cond; 100
120 econd 1 p from he commenc m nt f he iu-h
} tion 0 compI l' co r. In hil ren n 1'CO i, occurred
oon l' han in dult.
omp} n h ia i
c nd of comm nCln a
b Ii d h
h
Thi ca.n be hown by simple
about IS centime re
o and the other
merc~ria.l rough. I
n
U E F ITR o~ IDE I:r DE T L PER TIO 4
ure
iii. . I,. n
of inhalin
n h two it i furth r
uffoc' ion-wi hou
a t I' th hiI'd
during th proc
[PI. o~ IDE I ID IFER .
ODE OF ITROU 0 IDE
oxid av
rent
Z E.
to
of
b com of
I .
Op'llm-It O1'igin-Oon''ltituent - hief alkaloid - o'rphine
- areoti .De t-Poi,'onous aeti01 -E.ifl t on the .pinal
cord, heart, & ,-It po 1'. of l ening the p ri taltie
movem nt of the inte tine- a'reot 'ne, Thebain, and
od ine- ubcutan OIl inJ etion of morphine-It advantage
and d' ad antage -E retion of 011J!t 'Il -How to
r c gni 't and to detennine 't pur'ty- conic a id, a
m. an of d te1'mining the re ence of opium and 't . tract
-Opi an moking- 'ub t 'tut for opium- onnabi' Indica
-Ha, Tti ch-Lactucar'um"
Y ET
EGET BLE LK LOT 4
animal 0 ni m he remain to con id rable e t nt
unchan d, 0 hat hey can be de ect d fter ard in h
urin . kalie gener lly precipita hem from th ir aIt :
hu if I c; dd cau ic od 0 olu ion of cinchonine
h ·drochlor t , the cinchonine i precipitated in floccul n
me. The lk loid. ar pI' cipita ed b numb l' of
l' , tho e mo employ d being pho pho-mol b i acid,
pot. io-mercuric iodid , and iodine in a olution of po a -
lum iodid. rIh la r reagent cau e a thick, 1'0\ n
depo i hi b i in oluble h n added to a drop of ulphuric
cid. ach alkaloid ha i own p cial l' ctions by which
i c n be id ntme ; wi home of the e w hall h 0
d aI, an fur b r refer nee will b made 0 hem.
n lkaloid con i t of c rbon, hydrogen nd nitroO' n.
10 f h m con in 0 g n 0, but hi i not n n-i
I ch l'
RPH E.
proce in plant re
excretory product .
ue cha.n in the pI nt, re
re not turned to any further
pon e;
limb ; with COn inuou
he ill open hi eye.
EFFE T F PHI 51
occur
he
• TH RT.
F THE I E Tl E • 3
re t, note the qu ntity of air expired In thirty
cond , and obtain th following results:
230-200-220-200-210-200-210 c.c.
lmo t immediately after the injection of ·01 gramme
(. I r in) of morphine hydrochlorate into the jugular vein
e ob erve a lower mo ion of the index, nd read off-
90-100- 0~C>-90-9C>-90c.c.
con iderabl reduc d by
ea ily be inexperiment
he
ai
F RP LIE •• TEE ETI •
ID n 0 th in e in took pI ee?
re no IonO'er in conne ion
he t nth dafter ection of the
,mol'phin h eked the mo emen
THEB E. 55
from
cutadi
-
of
on
of
d
T E LOID F PI
PREP R TlO ' PlU • 57
a reddi holution
in
im m r m rphine
DE rn.
ip c cuanh and i ht
h ving
o long a we 1'e
me ine modifie
PTO BY ODEI :TE. 59
he me t,ime poisonou re uIt have been produced
b 00 I rge a do e. child of two year old had
0·1 gramme (1·5 grains) given to it in the cour e of a few
hour. The following symptoms are aid to have been
produced :-a death-like pallor, coldne of the limb, the
pul e and heart-beat imperceptible, the abdomen di tended,
the e e fixed and taring with widel dilated pupil , and
dr ne of the mucou membrane . timulant w re dmini
ered, and after a few hour the child rallied.1
The do e of pho phate of codeine i about three time
ha of hydrochlorate of morphine. From 3 to 6 cg. (t to
of a rain) ma be administered two or thr e tim a day
wi h dvantag. The erman Pharmacopreia ha fi ed
ramme ("5 rain) he ma imum ingl do ,and
o· ramme (6 r in ) he m imum quan i y 0 b given
·n , n -f Dr hour .
H"1 DEI I \D... II I T TIO.. l' ~rORPHINE.
HYFODER II 1 DMI I'TRATIO OF ORPHI TE. 61
I J
BOUT EOU JEOTIO OF OR HI E. 63
IT.
i dr whack.
morphine, and
THE RPHI E H BIT. 65
2 )
In u r 1-
TE •
OPIU 67
ervou Di e e at Halle, did not even di ork.
1
at ry e r ct of opium i largely n ed
bein inhaled into the lun
n denie th t ny of he
crib d ri ing fr m hi r c-ium
mokin ha b n ron I
of nervon di or er .6
comou
ht 0
uli r
o ill DIOA. 69
mm or mor
n
of opium give th ame
di tinctl a i he ca e ith the
Wini r 10
ion 0 he bo
BY HA OHI H.
EFFEOT PRODUOED BY R ORr OR.
:u6.
71
7 I "DI HE IP.
n hi orrowing comi
ord r. It ha
harmacop i , and in
ract nd the tincture
I DIAN BE P. 73
of liquor from ha chisch is prohibited throughout Egypt.
The door of those coffee-houses or inn where it is supplied
ill be walled np, and their proprietors imprisoned for three
months. All articles containing haschisch will be confi cated
and publicly burnt."l And yet, even at the pre ent day,
he habitual indulgence in hemp is the cause of many in-curable
mental disorders in Egypt, Turkey and A la. It
i one of the cau es that ha de troyed the old warlike
n rgy of Ea",tern nation .
o long a we are unable to obtain stable and active
r paration of Indian hemp it has merely a scientific
in ere. t.lI The ame may be aid a] 0 of LACTUCABIUM, the
dried milky juice of La tuca virosa, the trong-scented
Ie uce ( at. Ord. Compo it00) , which wa at one ime
fficinal. The following group of hypno iCB r cently
rought into u e ha upplied he ant that formerly
i t d, and in my opinion enable u to di pen e with uch
uncertain preparation tho e of annabi indica or
L c uca viro a.
I From artin s 'Ph8ormakol. med. S udium iiber den auf.,
1 6 . 4.
n thi h ad compar th 180 t publication on he ubj c by
of P ri in th • Deut ch. m d. ochen chr., 1890 . 679 fl'.
HL R L H DR TE. 75
place may sub-
. ~.
7
of he drug will have com-
TIO OF CHLOR L. 77
he former case from 5 to 10 grammes (75 to
in the other from 1 to 3 gramme (15 to 45
more and more profound, the
4
ion of he h ar ,
rin 0
hich i
D E "'D ODE F o HL L. 79
80 TE T FOR THE PURITY OF OHLOR L.
into olution of one part in ten of lcohol, hould only be
tin ed r d on dryin , and after acidifying the above olution
with nitric cid, i hould not, on the addition of nitrate
of ilver, imm diately becom cloudy, owina to the formation
of chloride of ilver. The e two te ts are to determine
the pI' nce or ab nc of an e ces of hydrochloric acid.
I pply these test here, you ee that there is a slight
I' d nin of the litmu paper at fir ,whilst with the other
t t a Ii ht opale cence appears in the te t-tube; some
h rochloric acid m y exi t even in the be t preparation,
or it may be developed on e po ure to the air, and especiaU
to baht.
h n hated on the platinum-foil chloral h drate should
vol ilize, and hould d v lop no inflammable v pour.
rate of chloral, po e ing a neutral or even an alkaline
reaction from admi "ture wi h oda, ha been introduced
into commer e. On heating uch a pecimen there i a
whit I' idue which on bein tested prove to be odium
chlorid and oda. If any inflammable vapour i dev loped
it ari from the pI' nce of chloral alcohol (C2C130H +
RaO), the local effect of which on the tomach i tronger
tha that of chloral h dr e, and therefore detrimen al.
HLORALU FOR In T hlora1 formamide, i a pre-
Ion hich ha r c ntl becom officinal. It con i ts
hit brilli n, odour! cr t 1 of a Ii h I bitter
'V hich melt at I 14- t I IS°, and ar lowly solubl In
o P I' of I' or in I'5 P rt of alcohol. Its
ment a a opormc wa propo d b v. ering in
00 .
Th form ion of chior 1 h dra e i indic ted by he
pp r nce of uro- bIoI' lic acid in he urine, and he
orm ion of ammonium formi te accord ith chemical
PAR LDEHYDE. 81
facts. It has been further assumed that leep, which i
r nquil and not too profound, is produced by the gradual
eparation of the chloral hydrate, and that owing to
the formation of a compound of ammonium-a I hall
point out to you when I corne to discu s the compounds of
ammonium-a gentle stimulation of the ympathetic and re-piratory
nervous centres simultaneou ly takes place. Th
con equence of the latter is that in animal , during th
leep thu produced, the blood-pre sure and the re piration
are lowered much Ie than when hydrate of chloral alone i
employed. Thi property D'ive chloral formamide a pecial
advantage as a soporific where disease of the vascular sv tern
exi t . nd it po sesse a furthel' advantage: chloral
formamide i not caustic like chloral hydrate, and i therefore
better tolerated by individuals with sensitive tomach.
From I to 3 grammes (15 to 45 gl'ain ) produce a leep
that generally pa es off without any after effect. : 4
grammes (a drachm) i given in the German Pharmacopreia
a the maximum dose. It may be admini tered either
di solved in water or a a powder.l
P RALDEHYDE was recommended a a soporific in I 3 by
V. Cervello, of Palermo.2 It is a clear colourle fluid, ha
a neutral or very lightly acid reaction, a peculiar ethereal
bnt not penetrating odour, and a pungent refr hing ta te;
it pecific ravity i 0'99, it boiling-point 123° to 125°.
ith 9 par of water it form a. olution which i rendered
tnrbid by heat. It mixe in all proportions with alcohol
and ther. It i obtained b treating ordinal' aId hyde,
H3. 0, at a medium temper ture with a tronD' mineral
acid· he aldeh de i thereby c nverted in 0 a polymeride,
that i hI' e molecule cond n into one to form ( ;2H4,0h.
In warm-blooded animal paraldehyde, like morphine, act
fir t upon th cerebrum, thpn on the re piratory centee and
h pin I cord. Large do e of it paraly e he re piratory
c n r ,and a are ult put a top to re pira ion and the ac ion of
1 Fl'om the numerou paper upon chloral formamide I would
el t: E. Kny, 'Tb rap. onatshefte,' I 9 . 345' . Lang aard
ibid. . 461; . erin u. Zuntz, ibid., .565' E. R icbmann 'D utscb
med. cb n chI'. ' 1 9, 0.31 (from Rie el' Klinik).
2 • Oer 110, rchiv f. expCl·iment. Pa.th. und Pharmak. 1882,
B . vi, s. 265.
6
PAR LDEHYDE.
I , ould r £ r th r ader
. 40; . v. oord n.
the h ar. The heart' action can be re tor d by artificial repira
ion; i i ther fore not dir ctly affected by paraldehyd .
do e of fr ill I to 4 erramme (IS grain to a drachm)
pI' duc tranquil 1 p in man without cau iner pI' vious excit
m u or cer bral conere tion. The patient u uallyawakes
cl ar-h ad d an without di aerreeable after-effect.. It doe
not produc con ipation, a i he cn, e with morphin,
nor d pre ion of the heart' action like chlor 1 hydrate.
On th other han, paraldeh de h the following di advan
a :-1 irrit lie the mucou membrane of the laryn
and of the tomach, if from any cau e the e are already
aff ct d. Th y tem peedil become accu tomed to it, 0
ha the do e mu t be increa d. It price i rather high.
Th odour of he breath for at lea t twenty-four hour after
takinO' h medicine i unpl a ant.l
If tb admini tra ion of larg do e of paraldehyde i con-inu
d f01' an 1 n h of time the brain become affected.
Th ymptom approximate very cIa e1 to tho e produced
by alcohol; remor, 10~ of memory and rea OD, delirium,
hallucination ,an pilepti£orm attack 801' mentioned. E.
Frohner!! ha , mol' over, ob erved other poi onou effects on
hoI' n dog, viz. he forma ion of methremog10bin in the
bloo he d eneration nd de truc ion of th red corpuscle>
h a aO'e of h m tin into the urille, with diminution of
11 moun f th lement in he b100d-re uIt which
r imil r to ho hich P rog 1101, ni ro-benzol , pota-ium
hlori nd 11i d ub nc are known to produce.
Th r ducin c ion of p l' ldeh d -tha i, it power of
r adil combininO' i boO' n-i he cau e of i injuriou
if u h bl urn n lood, ho vel', i not 0
in hi a that of th animal above men-ion
d· 0 uch h e b n b er d in
m n nd, wi h ed h rdl r b £ ared
£1' m h u u 1 do
Th b form in
an olution
A lYLE E HYDRATE. 83
ou ht not to be given in a concentrated form, as it then
cau e a en ation of burning in the mouth, and al 0 affects
the tomach. The arne rea on render it un uitable for
ubcutaneou injection. ccording to the German Phar-macopooia
5 C.c. (85 drop) is the maximum ingle do e and
10 C.C. (170 drops) the maximum quantity to be given in
twent -four hours.
YLE E HYDRATE 1S the name of another oporific
belonging to the methane serie. It ha the empirical
formula C5H1ZO, and from its chemical behaviour appears to
be dimethyl-ethyl-carbinol j that is to say, methane (CH4)
in which two atoms of H are each replaced by CHg, one atom
of H by CZH5, and the fourth by OH j therefore it rational
formula is (CHg)z.C.CzHs.OH. Its character, according to
the German Pbarmacopooia,are as follow :-a clear, colourless,
volatile fluid with a neutral reaction, a peculiar ethereal aromatic
odour and cau tic ta te, oluble in 8 part of water,
forming a clear mixture with alcohol, ether, chloroform, glycerine,
and fat y oil, boiling at 90 to 103°C. (194° to 21T4°
F.), and having a pecific gravit of 0'815 to O' 26.
It effect i purel soporific, without cau ing appreciable
change in the re pir tion or circulation, and without di turbin
the int tinal activity or the general condition. The
medium do e for a strong adult i 2 gramme (30 gr in). It
cannot b nb titut d for morphine in the leeple ne that
i cau ed by pain, nor i it 0 ea ily tolerated in irritable condition
of the tomach a i the la tel'. n thi account
amyl ne h drate i always giv n with a large amount of liquid,
no Ie than 50 C.c. ( bout 4 table poonIul). Extract of
liquoric erv to cover it ta te j it is readily taken in
1 in c pule j 4 c.c. (a drachm) is the maximum ingle
do e. It rna al 0 be admini tered a n enema (5
i h 50 of at l' and 20 of mucilage). On
accoun of i irri a ing prop l' ie when appli d locally, it
i not a uitable prep ration for ubcutaneou inj etion.
In mo l' te do e am 1 ne h drute chi fl aff ct he
c rebrum j in 1 rger do e it ff ct h pinal cord a well.
fle cit bili i 10 , he re 'piration become le fre-quen
and la t cea ,complet paral of the heart
m anwhile bing gradually de eloped.
ULPHO AL.
my1 ne h'dr te wa introduced into medical practice in
7.1 inc that time it qualities have been much dis-n
, and in all e ential points the original estimate of
h m ha been confirmed.
Th employment of ULPHO L a a ubstitute for morphia
i of more rec nt da e: it n e wa sugge ted by . Ka t,2
i mode of production by chemical proce e having been
pr ViOll ly di covered by E. Baumann. The German Pharmacoprei
thu de cribe it:-colourle ,odourles, and ta tele s
pri matic cr tal, which are entirely di ipated by heat; one
par of it form neutr 1 olution with 500 parts of cold and 15
part of boiling wattlr, with 65 of cold and 2 part of boiling
alcohol, al 0 rvith 135 parts of ether. It melt at 1250 to
J26° O.
ulphonal, (02H5 °)...0.( HS)2' is an oxidation product
r uiting from he combination of ethyl mercaptan with
ac t ne, and con equently may be regarded as methane (OH4)
in which two atom of H are replaced by two molecules
of di-e h I. ulphonic acid, and the two other atom of H
b two mol cule of methyl. The empirical formula i
7 16 20. It i l' garded much in the ame light as
tIl lene h dr te, but a a rule leep is not induced until
e 1'801 hour after i e hihition. It Ie er olubility in
h in e tin 1 canal i probably the explanation of thi ,
hich i di inct drs. hack to it u e. leep ha ome-im
not foll ~ e he do e for ten hour ; when it did
t ke pI c i ch rac er w perf ctl n tural. The variabl
ff c hi h iv u do e produc s upon th ame individual
m be ociat d wi h thi unc rtainty with l' gard to it
b rp ion· n ime 5 gr mme (75 grain) may be
in ff ctu 1, anoth round Ie p m rtl ult from
·5 r mm (TS r in ).
ulphonal do not pro uc the di O'ree hI after-effect
which folIo he mini r tion of morphin ; on he 0 her
h n ,in be 1 pI n cau ed b p in it i powerle to
pI' uc b 0 hin ff ct on he br in , hich i induced
morphine. nlike chI l' 1, ulphonc 1 ha n irrita ing
ct on h u, nor 0 i e en in large do e affect
rin , Th rap u i h ona h fte, 18 7 8.249.
t, ' .B rlin. lin. ochenschr/ 18 , . 309.
TRIO L. 85
he circulator sy t m. A transitory cutaneou ruption
ometim follow it u e.1
om time after its administration, e pecially in women,
b matoporphyrin, a derivative of hremoglobin which contains
no iron, appear in considerable quanti tiE', in the urine, and
give it a dark red tinge.2 ephriti may 0.1 0 follow the
longo-continued u e of this remedy.
It i be t admini tered as a powder, in do e for adult of
I to 3 goramme (15 to 45 grain). The German Pharmacopooia
fixe the maximum do e at 2 grammes.
TRIO AL i. the name of a new preparation which may be
reg-arded a ulphooal modified by the ub titution of a
molecule of ethyl for one of the molecule of methyl in the
compo ition of the latter. It occurs in colourless, glittering
tabular cry t 1 , wbich have a omewhat bitter ta teo It di -
olve in 320 part of cold water, and more readil in warm
water. It i ea il oluble in alcohol and ether. leep is
induced more quickly aft l' tl'ional than after sulphonal,
and unplea ant after-effect are so rarely produced that at
pre ent it i regarded as the b t hypnotic. Hrematoporph
rin, however, appe rs 'ometime in the urine after its
admini tration. an hypnotic it may be given a a powder
in ingl do e of I to 2 gramme. (IS to 30 grain ), bu t like
other narcotic it i injuriou if taken 00 frequen ly.
T TRO L i a ulphonal which contain four molecule of
eth 1, and act in a imilar fa hion. It i , however, Ie
oluble th n trional, and h a more uoplea ant ta e. Its
u e, therefore, rna be dispen ed wi h.
1 G. rkel, I lincb. m d. Wochen cbr.,' 1889 o. 26.
2 koi I ederl. Tyd chr. von Gen e k 18 9, ii, 413. Ranking
nd Tardin ton I Lane t I 90, ii p. 607. lk w ky, I Z it chr. f.
physiol. Ch mie' I 91, Bd. xv . 286. Garrod, I J urn. of P tboI. and
Bac r., I 93, vol. i, pI. ii. In thi paper it i d nied thnt sulphonal
i erie to tb pl'esen of brematoporphyrin in th urin.
FRO RPHI E D HLOR L HIDR T.I!J.
DIAG 0 IS OF MORPHI E POI 0 I G. 87
took tho fir t powder, became speedily comatose and
cyanotic, and in a short time expired.
A young physician prepared a olution of I gramme of
morphia in 20 C.C. of water, to be used for ubcutaneou
injection, and had it labelled (( suo nomine." His yringe
h Id about I c.c., and he intended to inject one tenth 01'
one fifth only of its conten 5, 0 as to admini tel' 0'005 or
0'01 gramme of morphine. But the first time he u ed the
ring he forgot, after filling it, to fix he check-screw, and
on pI' inD' down the pi ton injected the whole con ent ,
0'05 (1 of a grain) of morphine, under the patient' kin.
He had carcely left the hou e when he wa hurriedly
'ummoneu back, to find hi patient unconsciou , with feeble
re piratiou and small pulse. The mi take wa. imm diately
recogui. ed, and fortunately was not followed by any injnriou'
effect upon he patient, though it wa not without
detriment to the phy ician's reputation.
Th DIAG 0 IS of morphine poi oning is ea y if the
corpus delicti happens to he di cov red. reparation of
opium are recogni ed by their characteri tic ouour, if this
ha not been de troyed by the addition of 0 her sub tance .
'I he meconic acid reaction al 0, to which I have already
r ferr d, may b employed to detect the pre ence of opium
in an 'olution that may be left or in any matter that ha
been vomited. In such a ca e the vomited matter bonld
be filtered, th fil rate concentrated if nece ary, and tben
fe, drop of a olution of the percblol'ide of iron added.
11 tbi can be done vel' quickl, but the ca e may run too
cute a cour e to allow time for the inv stigation.
F iliug a ru~twor hy account of the preceding hi tory
of th pa in, and in th ab ence of the corpu delictI:,
poi oning b morphine ma be mi -taken for that which
1'e ul from larg do e of alcohol, of cbloral, carbonic
o ide, or coal ga . e' rly 11 the mptom ,hich ha e
b en de crib d ar pre ent in poi oning from th e ub-t
nc : one onl i u ually ab nt-the strongly 1nark d
m.yo i, or con raction of the pupil, hi h i in ariably
pI' en in morphine poi onin , nd which pa e off only in
he la t aD'. It i probably due to condi ion in the
btain, and not dep ndent on local cion uch a i produced
by ph
poi 0 ing
bre th b
Dr OF MORPHI E POlO I G.
are-In
be
.35°.
TREATMENT OF CA~E OF MORPHINE EOI I G. 8D
fatal, an average lowering of the blood-pre sure from 129 to
91 mm. of mercury has been noted.1 And my a i tant, H.
Heubach, under the ame conditions, in ix experiments on
dogs, noticed that the pul e ank from 120 or 130 to 42.2
It ha been further urged again t m view that the diminution
of the blood-pressure arose from he animal being
bound down for hours, but I could easily prove that, by tying
an animal down for a given period, the blood-pre ure is only
slightly affected, and in tead of being dimini hed i inc1·eased.
In the TREATMENT of cases of poisoning our fir t bu iness
is to remove any poison that may be pre ent in the tomach.
In .lighter cases vomiting may take place spontaneously,
and may be promoted by tickling the fauces. In more severe
ca es morphine very soon completely suspend the excitability
of the nerve-centres in the medulla oblongata, and
even metics produce no effect. It i better not to waste
time with them, but at once to wash out the stomach. 0
other proceeding is of any u e in these ca e .
If strong emetics, especially the mineral one , remain in
the stomach and become gradually ab orbed, they help to
Ie en the strength of the patient by still further lowering
the activity of the already enfeebled heart. Many of the
unsucce sful ca es which have be n recorded give the
impre ion that the powerful emetic employed had ouly
int n ified the poi onous action of the morphine. The
injection of apomorphine, which has be n recommended as
an emetic, and which even in mall do e act ry
energetically, ma still cause vomi lng, but it i a eriou
que tion whether he combined effect of two such extr mely
low ring agen s does not render he patient's condi ion
more critical than before.
In ca e of poi oning by other officinal alkaloid TANNIC
ACID m y be admini ered for he purpo e of rendering th
poi on still in the tomach less oluble, but it i of little
ervice in morphine poi oning.
I C. Binz, "U b r den arteri lien Druck b i Morpbinvergif un "
'Deut cbe moo. ochen chr.,' 1879, s .613 und 627; und 1880, . 149.
S Reub ch ' rchiv f. exp r. Pathol. und Pharmak., 1877, Bd. viii,
.38; . Fick,' erbandl de Congre e fur inn. Med.,' ie baden,
1 86 s.92.
90 D~ OF RTIFIOIAL RE PIRATIO •
If, for
pump mu
a h d ou
paD'
pIne
ch. . mmluD
hUll r • Eine
del' 'in tlich n
,319.
of
how iO'n of failing, imRTIFICI
L RE PIRATIO •
hould only be attempted
it, In a ea e of poison-
ARTIFICIAL RE PIL{ATIO • 91
b ck) and an as i tant should bend tbe thigh firmly upwards
o a", to relax the abdominal parietes.
h11 t adopting the e variou mea ure for producing artificial
I' piration) the maintenance of a free opening for the
pa age of air to the lungs mu t not be forgotten. Draw the
tongue forward as far a po ible) fi it in thi po ition)
p-ither with the foreep ) or in default of the e, b a thick
thread pas ed through it; pa s the index finger into he
phar nx, feel for the epiglotti ) and pll h it a high up as po -
1 Ie. 'J'he following method (Heiburg) i generally to be
r commended:- n a i tant stand in front of he patient,
lac bis thumb on the upper jaw close to tbe no e) and
curving hi finger. on both ide behind the angle of the
low I' jaw) pull it vigorously forward. By pulling the jaw
f rward in thi way he tongue and hyoid bone are al 0
thrown forward; the epiglotti , owing to the ligament
b tw en it and the hyoid bone being put on the tretch) is
aLo drawn forward, and the pa age to the laryn i
k pt free. Thi ha been proved by experiment on dead
b die.
It ha been found that artificial re piration i not ufficient
0 effect the re-establi hment of the HEART'S ACTIO
when its impul e i no longer perceptible.l on equently
in all ca of poi oning of hi character pre ure Olu t
appli d to the h art in uch a wa that it may be
alternatel rnp ied and again fiUe wi h blood. In this
w y th circulation 1 tarted: the heart begin one more
o contract, and th l' pirator c ntr which wa almo t
mpl ly paraly d) receiv fr b timulu froUl the
bio that p ~e to it.
In the v l·iou. treati d aling with rnorpl1ine poi oning
the pplication of all ort of count r-ir1'i an 0 the kin is
r commend a an importan p rt of he rea m n ) but
It count r-ir1'it nt are of doubtful value when he
pa j n) cond i ion i 0 critical.
hi brin me to a point in the rea ment hi h i carcely
r refer1' d 0 in l' a i e on poi omn ,name]', the value
8 a re orati e, of AR'I'lYleJ L W R TH co '1'1..: 00 LY APPLI D
to he pa ient' body.
1 Bobm,' reb. f. exp 1'. Path. u. Pbarmak.• I 77. Bd. viii B.6 .
E F THE W H.I B. TH
n inquir
D OLD DOUOHE.
ar
he
m a
appli d
bon i
f'cam in uffich
ime.2
EFFECT OF TROPI E I ORPHI 93
The action of the central n rvou tern mu be main-tained
by th internal Admini tration of '1'1 ULA T
I refer in he fir t place to trong hot infu ion of tea
and coffe. They contain two timulant, caffeine and an
t romatic ub tance.1 If caffeine in MODI~RATR do e ubcutaneou
ly injected into animal it produce a gen ral and
active re Ie ne. , a more rapid and deep l' re piration,
increa ed pul a ion of the heart, increa ed blood-pre ure,
and a ri e of temperature. 'I'he e effects were rikiDgly
manife ted on doO' suffering from poi oning of a imilar
natur , namely, that cau~ed by alcoho1.2
hould there be danger in delay we mu t uot he itate to
mploy the most powerful of all internal timulantsA'I'ROP]
E.
If a mall do e of atropine, a few milliO'ramme ,be ubcutaneou
I injected into a dog in which, amonO' t other
ymptoms following a large dose of morphine, there is
greatly dimini hed blood-pre ure, the pl' ure will be increa
ed wofold or more within a few minute. Thi i due
to the greatl increa ed number of pul ation ; the beat of
the heart are trebled or quadrupled, owing to a temporary
paraly is of the cardiac branche of the vagi.
The e branche of the vagi are the inhibitory nerv of
th heart; they serve principall 0 reli ve he br in. If,
in con equence of any timul tion, th h ar drive the
lood too largel and too violently into the unyi lding cavity
of the kull, the whole brain i hereby imulated. ut by
TJ ULA'fl G he va i a slower movement of th hart'
ac ion i produced, and one cau e of the exc of blood in
h brain i removed. By PAR LY I G he va i ju he
oppo ite eff c i produced; a quick l' mo emen , wi hout
d fective contrac ion of th hear, take place, and the
rt 1'ie become filled wi h blood.
If the agu i. po ed nd divided, nnd i p ripheral
lld timulat d with n induced curl' nt of 1m: po er, the
he. r i immedi ely brought 0 a ,tand ill, or at Ie ·t th
numb r of pul a ion icon iderabl dimini b d. If orne
. Binz • B i di e zw' Kenntni del' Kaffeeh ndteil" 'ch.
f. xp r. Path. u. Pbal'm~ k. 1 7 Bd. i , .31 .
. Binz ibid" . 3 -3 .
T PI E TIDOTE.
In
ha
previoll 1y b n admini ter d to the animal, the
CUlT llt on h ,O'u i nil. The atropine ha
o p ra1 ed he end of th aO'u that it is
o conduct, any timulu to tbe mu cular i. ue
1 nr ther fore, why atropin increa e he bloodnorm
I condi ion, or les ened
not overpower or re train
pre ure, a i he cave with oth r
0·01 gramme
oon we notice
ATROPI E A A A 'rlDO'l'E. 95
ing the hremodynamometer it can be easily shown from the
tracing on the kymograph that the increased number of
pulsations corre ponds to a doubled arterial pressure.
Here is such a tracing from a young dog weighing
2580 grammes.1 Its blood-pressure was, by the injection
FIG. 2.
A.tropine injected------- <::> r-of
O' I 5 gramme of morphine lowered to 60- 0 mm., the
pul e wa 40 a minute, n irregular. eventy cond
. Heubach " nta ni rnu zwi chen orphin und tropin,
, rcbiv f. expel'. Pa h. u. Pharm., 1877, Bd. viii, 8. 40, Pharmakol.
In t. Bonn.
LUE F E PERI E T
racin commenc done
£tel' for
STEYOR I E A A A TIDOTE. 97
were fully dilated, the heart-sounds normal, the pul e 80,
but the patient was still comato e. Afterward the nervou
sy tem gradually recovered its sensibility to external impressions.
The following morning, twelve hours after the
administration of these large doses of atropine (altogether
21 times the German maximum dose I), the condition of the
pulse, pupils, and respiration was normal. There was no
mention of headache, but there was tingling in the finger
and toes. ome hours later the mydriasis reappeared and
10. ted for some days.
Thi is only one out of many cases recorded here and
abroad.l There are cases, too, that give a different record,
but they were improperly managed and have been obscurely
described.2
There is nothing specially characteristic in cases of
poisoning by any of the more recently introduced oporific ~
such a chloral hydrate, &c., with the exception perhaps of
paraldehyde. In these case it is only the previous history
which can help us to a diagnosis.
The same treatment must be adopted as in ca es of
poi oning by morphine. Luch inger has shown that 8>
heart, the action of which has been paralysed by any of the
ordinary cardiac poisons, can, in the early stage, be stimulated
by atropine to renewed and often to vigorous contrac
ion. This effect is not in his opinion dependent on the
removal of any ob truction to the action of the heart, but i
due to it direct stimulation.s
Liebreich has specially recommended STRyeR 1 E a an
an idote for chloral. The idea was suggested to him by
ob erving the beneficial effect of chloral in a ca e of
rheuma ic trismus and tetanu. He experimented upon a
rabbit and confirmed his hypo he i that the conver e would
prob bly hold good.'
1 John ton, U Cases showing the Effects of Atropine a an ntidote
o Opium,'" ed. Times a.nd Ga.z.,' 1872, p. 269; 1873 p. 175.
2 Compare C Archiv f. klin. ed.,' 1887, Bd. xli, s. 174.
I Luch inger, CArchiv f. exper. Path. und Pharmak.,' I I Bd.
iv, . 374.
• O. Liebreich, C on taber. d. Berl. kad. d. is en h. I 69~
.872 •
7
98 TRYOB I E A A A TIDOTE.
It may be O'ranted a theoretically possible that strychnine
can act ben fici lly in chloral poi oning. Chloral depresses
the vaso-motor centre in the brain j trychnine stimulates
it : 1 the former dilates the arteries, the latter contracts
them; th former lowers the blood-pressure, the latter
increa e it. In the narco is induced by chloral the
e citability of the respiratory centre is lowered in an extraordinary
de ree j in trychnine poi oning it i just as powerfnlly
timulated. The re ult la t mentioned can be seen in
any anim I previous to the appearance of the spasms; the
re piration become more frequent and more profound.
hat bearinO' the e f ct -gained from experiments on
animal -m y have on the point under di cus ion must be
d cided by furthet' ob ervations on the human subject.
hil t making such observations it hould never for So
moment be forgotten that powerful dose of strychnine are
uncontroll bl in their effects, as we shall learn more fully
1 er on. I, for my part, should only have recourse to
trychnine (0'002 gramme, i. e. -h of a grain, a few times
ubcutaneou ly) if, in a case of great danger, neither a hot
b th ith cold douche nor atropine was available.
yer, c tudien zur Physiologie des Herzens und del' Gefiisse,"
i zun richt d. k. k. d. d. i ensch,' 1 71, Bd. lxiv, s. 657.
2 .Ohri tiani, c onatsber. d. Berl. kad. d. Wissensch.,' Feb. 17th,
1 I.
VI.
Pota sium b1'omide-Its discovery and introduction into medicine-
Experiment with it on healthy individ1.lals- econdary
~Uects-Sodium b1·omide-.Ammoniurn bromideZinc
oxide-Its '/.tse in the1'apeutics-Poisonous actionExpe'riments
with it-Othe1' officinal prepa1'ations of zincHemlock-
Its prope1,ties-Death of Socrate from hemlock
- Jubsequent experience of its effect on man-Experiment
on animal -Therapeutic value of hem'zock-Oonium
hydrob1'omide-Hemlock sometimes mi taken f01' culinary
he1'bs-Water-hemlock (Cicuta virosa)-Ou1'a1'e-Its origin
- tatements ofHumboldt and of other travellers-nlu tration
of it general action on warm-blooded animals.
Analysi.~ ofit effects on the frog-Ou1'wrine- Variablene
of curare-Its therapeutic '/.t8e,
WE now come to a group of remedie differing entirely
as to their source and in their outward appearance from the
cerebral edative which we have previou ly con idered, but
agreeing with them in ome mea ure a to their effect .
The e are the bromide, of which POTAS IU BRO IDE i the
one mo t employed.
Its compo ition i KBr; it con i ts of colourle s, cubical,
hining cry tal, which are not decomposed on expo ure to
the air. It i oluble in 2 parts of water and in 200 part
of alcohol. ben a solution of it in water to which a little
chlorine ha been added, is agitated with ether or chloroform,
ei her of these will on epar tion exhibit a red colour,
hich i due to the liberated bromine. Tar aric acid added
o it in exce s give, after standing for ome time, a white
cr talline precipitate of acid tartrate of pota ium j the
, upernatant fluid contain h drobromic acid, he followin
decompo ition h vin taken place:
Br+C4,H60 6= C H50 6+HBr.
100 POT IU BRO IDE.
he phy ici n ha b en in a very different
pre iou 1y h c e ith regard to
pil ptic a t ck , for in former ime there
f w year after the di covery of bromine in 1826 by
BIard, n apoth car of Montpellier, the u e of the
pota ium It a medicine came into great vogue as a
remedy among rench phy ician. Being chemically similar
o iodine, the newly di covered element had a signed to it
he already well-known therapeutic properties of the former,
and it a u e in crofnla, syphilis, and for glandular
wellin , uch a goitre. On account of the corrosive
ffect of pure bromine, the potassium alt, corresponding
to that of iodine, was prescribed, and wa taken internally
in quantitie mounting to 30 grammes (460 grains) daily.
o improvement took place in the above-named diseases
under he admini tra ion of the bromide, but its effects in
the ell' e do e on the brain were recogni ed. tupefac-ion,
giddine ,heavin of expr sion, difficulty of speech,
ag ering g i, dimini hed sen ation in the extremi~ies,
boli ion of r flex c ivity in the phar nx, were the only
re nIt of he e herapeutic experiments, which, in I 50,
Pnche 1 in Pari ermed Cf ivre e bromurique." Huette
no ic d uch a ompl e abolition of reflex activity in the
ph l' n , ha h ugge ted that the dru might possibly be
of ervice in urgic 1 operation .
rly I 5, ir ocock recommended bromide
ium for epil p y ; 2 but for ten ears it a rarely
e, nd i a only after the 1 p e of another ten
and after car fnl tud of the records of it
er I r number of ca e of that di ease-a
o ari hIe, nd therefore therapeu ically so decep-i
h th u efulne of he l' medy as unqu tionably
emon tr ed.
h80 time
h
f
.24' Hue te)' az.
TRE TME TT OJ!' EPILEP Y B POT IU BROMIDE. 101
eemed to be little or no po ibility of mitigating this frightful
di ea e. In the institution at Stephan feld, in 1 ace, thirty
evere ca es of epilepsy were ystematically treated with
large doses of bromide of potassium with the following
result. In 23'3 per cent. the attacks entirely cea ed during
its use j in 40 per cent. the number of attack decrea ed by
at lea t one half, in the majority of the e cases by more
than Ol1e half j in 26'6 per cent. improvement was slight or
doubtful, and only in 10 per cent. could it be aid that no
effect at all was produced.l
.A further erie of twenty-two ca es wa divided into
two groups. To one half ODIUM BRO IDE only was given,
to the other half only POTAS IUM CHLORIDE. After ten week'
u e of the e medicines to the amount of 5 gramme
(75 grains) to each patient daily, the odium bromide had
very noticeably decreased the attacks in several of the
eleven patients, whilst no distinct effect wa observed in
the patient treated with potassium chloride.2 imilar
re ults were reported from the institution at Pforzheim.3
Bennett, of Edinburgh, reported hat in 2'3 per cent. of
the patients under treatment with pota ium bromide the
number of attacks increased j in 2·3 per cent. no change at
all could be perceived j in 3 per cent. the attacks greatly
decreased in number and in violence j in 12 per cent.
they entirely ceased as long as the pota sium bromide wa
tak n.
In addition to thi, the effect which pota sium bromide
ha in many ca e of disturbed sleep is ea ily e plicable.
enator informs u that ven he leeple ne and re tI
ne of fever are reliev d by it to a greater e tent
han by any other remedie. Its value ha been proved
aloin many form of rigeminal neuralgia. It hI! been
1 C. S rk, I All . Z it chI'. f. P ychiatri i, . 29i.
'E. . eguin records imilar tatistic, ~w York Therap utic 1
c., I 78, 8th February. In oppo ition to hi ee . ander Cen-b
·albl. fiir die m d. i.,' I 68, .817.
3 t, I rch. f. P ych. und ervenkrankheiten,' 1875 Bd. v •
. 24·
" H. Bennet, ' Edinb. ed. Journal,' 18 I, vol. vi, p. 706.
• enator, I Der fi berhafte Proce s • Berlin I 73, . 2 7.
102 ITH POT IU BRO IDE.
e crib pecific for the vomiting of preg-nancy.
I
Clinical ob rvation of the effects of potassium bromide
had, a i 0 often the ca e, outdi tanced and preceded
'ci ntific inve tiga ion, for the re ults of the latter remained
confu ed and contradictory. Thi wa due to various
'au e. In th periments the effect of the POTASSIUM
con tituent wa either not taken into account, or the result
weI' ntire1y attributed to it. The experiments were made
on lMALS which, in compari on with man, are in general
much I en itive to he action of narcotic, at lea t so far
he c I' bral hemi phere are concerned; the experiments,
mol' 0 er, re m de on HEALTHY animal , without reflecting
that a heal hy nervou sy tem may probably be Ie s in£
luenc d by ny edative remedy than one which is
morbidly xcited; and finally, in many ca es the dose
mplo ed in the experiments was far too mall. rather
length eri of experiment from Kiel-revi ing all the
previou inve igation in the light of the increa ed experim
nt 1 and clinical experience that had accumulated
in th meantim - howed, how what had been e tabli hed
in the di ea ed, applied to the healthy, and furni hed an expI
na ion of ome of the peculiaritie which had been ob erved
in he ca e of nimal.
rom 10 0 IS gramme (ISO to 225 O'rains) of potasium
bromide dminist red to healthy oung m n in a
1 do , or in the cour e of a fe minu e, gave
o oppre ion nd f eling of warmth in he tomach,
liv ion, ligh nau ,nd liquid evacu ion ; further,
o front 1 hache of a dull, he vy char ct 1', a though
th compre e ; the ment I facul ie w re con-d
n h po of thou h ob cure. Thi
d for e era1 hour . peech a low and
nd 11 ble 1'e mi plac d; la itude
I'd impre ion re ob r ed, but
h ordin r n rcotic. Th roo of
he throa ha 10 t heir reflex
EOO D RY EFFEOT OF po'r IU BRO IDE. 103
activity; irritation of any part of the fauces did not produce
the slightest tendency to vomit. The temperature was
lowered from 0'50 to 1'20 C. (0'90 to 2'1
0 F.), and the frequency
of the pul e, which was irregular, IS to 37 per cent. ;
the arterie were soft and ea ily compre ible. The effect on
the temperature and pulse was most marked in the second and
third hour after the dose had been taken.
Control experiments with potassium chloride howed that
the effect on the heart wa always largely due to the potasium.
Later on we shall have yet to consider in detail the
very marked effects which the salts of potassium exert upon
the heart's action.
ODIU BRO IDE, taken by the same individuals in the same
manner a the pota sium salt, produced the same effect on
the nervous sy tem, but not on the pulse and temperature.
On animal it was 801 0 distinctly proved that the sodium salt
dimini hes the reflex excitability by direct action on the
nervous centres. The administration of pota inm bromide
to dog Ie sened the electric excitability of the cortical
ub tance of the brain.l
Inconvenient SECONDARY EFFECTS ari e from the prolonged
u e of potassium bromide.
Foremo t among these are disturbances of the digestive
function, but they can be modified or prevented by giving
the medicine in a large amount of water, and not on an
empty tomach.
Catarrh of the re piratory pas ages is developed or intensified
by pota sium bromide, nd may a ume a serious
character, owing to the simnltaneou abolition of the reflex
activity; mucn accumulate, expectoration is impeded, and
the bre th becomes offen ive. The mucou membrane of the
eye, no e, bladder, and urinary pa age may 801 0 be affected.
In the majority of c ses cutaneou ruption appear j he
mo common i AC of the calp, which from bing punctiform
m y become pu ular.j The bromide ha been detected
in the ecretion of the pu tnle j 3 he produc ion of the e is
1 P. bertoni, reprinted from' Lo p rimentale,' I 81.
2 ViI ' ierteljahrscbr. f. Dermatol. u. yphilis' 1875, Bd. i, . 17.
Kapo i ha n acn in a child at the brea t, ho e mother a takin
o ium bromide, •Ther peu. onat heft ,. 18 9, s. 468.
3 Guttmann,' rch. f. p' thoI. Anat.,' 187 , Bd. lxxi, .541.
10 ETHOD OF D I I l'ERI G POTA IU BRO IDE.
. 3 und 6~.
die rheini ch· tf··
u to the bromine only, for th yare developed 801 0 by the
t 0 otb r officin I compound, odium bromide nd ammonium
bromide.1 The acne m y develop into boil. .L. ettIe-rash,
imple and nodular erythema occur j these all di appear on
di continuing the medicine.
neral c chena may be developed by an immoderate use
of he bromide. The symptoms a sociated with it are
atroph , a allo compIe ion, commencing paralysi of the
e trellitie, 10 s of e ual de ire, diarrhwa, trembling of
the limb, foul and coated tongue, want of appetite, mental
pathy, eakne of memor , dilatation of one pupil, lateral
deflection of the uvula, and even delirium and hallucinations.
Th mp oms are u ually pI' ceded by inten e headache.
There i gr t diver i y a to individual u ceptibility in the
d v lopment of unplea ant effects. Recovery, a a rule,
gen raIl t ke place, e en from evere form of bromism.
c of hi kind ha been reported 2 in which, after
Jar do e of pota ium bromide had been taken £01' about
hr e ear to relieve leeple ne , m rked cachexia was
de lop , hich, ho ever, di appeared after six mon h8'
m nt.
ith l' g I'd to he I T TIO of pota ium bromide
pilep y-the di ea e in hich it beneficial action i so
ur n 1 n d d-the folio .n method, b ed on the re ults
f it n in ry large number of ca e , may be recom-m
n ed for adoption: s_a 10 p r cent. olution of pota ium
1'0 i in l' m y b pre cribed a foUo B: during the
fir hI' e table- p onful d il , mornin , noon, and
bout half n hour before meal j in the
four ble- poonfnl , di tribu d equall over
er t k D imm di ely befor or £ er eating;
k fi 1 - po mul d ily, and 0 on from
h qu D i ein incr db on t ble- poonfnl
t bl - poonful d il ; 0 h durin he fir eek
bl - poonful m be giv TI, during he econd
-ei h , durin he bird hir -five: more han
EFFECT' RESULTI G FROM THE OTIO OF POT IU. 105
eight table-spoonfuls a day ought not to be given} and this
amount must be discontinued or diminished if it seems to
cau e drowsiness or mental dulne . Should such a condition
occur} as may be the case in isolated instances} even ith seven
or ix spoonfuls} the quantity must be reduced. But if the
attacks cea e when three table- poonfuls} for example} are
taken during the day} then the dose must not be increased in
sub equent weeks} but mu t remain at three table- poonful .
Only on the reappearance of an attack} or if there are
warnings or indications of one impending} hould the dose
be increased by one table-spoonful daily} until such a quantity
-it may be four} five} i} even} or eight table- poonfuls
daily-has been reached as put an end to their development.
If for about three month here have been no attacks} the
number of doses may then be as gradually diminished as they
were mcrea ed. After the daily amount ha been diminished
to hree table-spoonful} it will be prudent to con inue this
do e for two to three month longer j the quantity can then
be decrea ed to two table- poonful dail} giving his for
perhaps three month} after which the medicine can be left
off altogether.
If he attacks recur} he me plan of treatment must be
l' ne ed. In many ca e patient cannot dispen e with the
pot ium bromide at all} nd mu t for ear habitually take
a mall quantity-two} three} or four table-spoonfuls of the
olution j otherwise the attack oon return} and with ev n
greater severity than before.
In the ca e of children between ten and sixteen years of
age we m y commence wi h three table- poonful } but must
not go bond i table- poonful at the mo t in the twentyfour
hour . ith childr n under ten y ar we may begin
·th t 0 table- poonful } and ad ance to four or five tablespoonful
in he wen -four hour. In the c80 e of very
young childr n he amoun mu t be ill further dimini hed.
If pot ium bromide ba' b en taken for a con iderable
ime} or e en for a few donI } b u c p ible per ons, it
h be n ob erv d to affec he HEAR'r unplea antly} the
pul e becomin feebl} irr aular} nd in ermittent.
Thi i doub Ie du to th pota ium} \ bicb} con tituting
33 pre n . of the 801 J m y very l' adil , giv n in tb
106 ODru , 10 IU , D 0 LOIU BRO IDE •
large do above mentioned, and in a form 0 easily
b orbable, e rt it d pres ing influence upon the heart'
action. or thi l' a on omu BRO IDE i preferred by
many ph ician.1
According to the erman Pharmacopreia this is aBr,
containing no more than 5 per cent. of water of crystalIi
tion. It i a hite cry talline powder, undergoing no
change in dry air, but somewhat delique cent under ordinary
circum tance, olubl in one or two parts of water
and in fi prof lcoho1.
BRO IDE, H4Br, is also officinal. It is a white
cry tHine powder, readily oluble in water, less so in
alcohol, nd ublimes unchanged on he application of heat~
Thi pI' P l' tion contain a larger amount of bromide than
an of th other compound -namely, 81'6 per cent. It is,.
how 1', the mo t a ily decompo ed, for by mere exposure
to he ir it oon becomes acid and yellowi h-effects due
to the form tion of hydrobromic acid and bromine. There
i i to be one drawback 0 it-n mely, that it exerts an
injuriou influence on th dig tive function. nother point
to be borne in mind is the endenc, hich the ammonium
n tituen i aid to po e , to produce pa modic con-raction
. t no pI' ci e inve igation eem to have
been made 0 how f l' he pI' nee of 18'4 per cent. of
mm nium in bromide of ammonium may mo ify the effects
of bromid in h tr atm nt of di ea e.
LOlU BRO ID al 0 h been found to act a a edati e
Oll h m tor, n ory, an r fle cen l' in the br in and
pinal cord, bo h in h 0.1 h nd di ea ed condition .2
The lin er of un t r-on- he- tein, ne r Kreuz-n
ch, con in in 7'5 gr mme 0 line m tter, di oIved
in 10 Ii r f r, 0'75 r mm f odium romide nd
1 0 of m Q'lle lum bromid . I i oub ful he her 0 m 11
II m unt of bromi c n ha 1 effect hen th
£01' ba h. Th moun contain d in th
pring nJ in larO' r-th i to , of 292
I T. J. Btl on,' L ce
, Eul nbur u. ut m
. ' I 73 .436.
• I 1.
a. Phy iol. u. . ensch.
IMPURITIE • 107
grammes of saline matter contained in 10 litre of water,
more than 2 grammes consist of sodium bromide.
Intentional adulterations of these salts, lessening their
therapeutic value, are so improbable that we need not con-ider
them. The tests given in the Pharmacopooia are sufficient
to detect such impurities. On the other hand, the
bromides may, from being imperfectly prepared, contain ome
bromate, or even hypobromite-that is, compounds of bromic
or hypobromous acid, KBrOs or KBrO. In acid media,
and consequently in the stomach, bromine would thereby
be liberated-a result neither contemplated nor desirable.
These impurities, as I here show you, may, if present, be
detected by adding a drop of diluted sulphuric acid to some
powdered bromide on a white porcelain slab, when the salt
immediately becomes yellow. Hydrobromic acid, together
with bromic acid or hypobromous acid, as the case may be,
i liberated by the sulphuric acid. They act on each other,
and bromine is set free.
In the first case we have-sKBr+
KBrOs+6H2S04=6KH °4+3HzO+3Brz;
in the other-
KBr+KBrO+2HzS04=2KH 04+2HzO+Brz·
Pure bromide does not give this reaction, as the re ul ing
hydrobromic acid, which is alone formed, is devoid of
colour.
Zinc, in the form of ZlllC oxide, ZnO, and of zinc
ace ate ( ",HSOZ)2 + 3H20, i ub tance which ha been
emplo ed from a very arl period for much the ame purpo
e a pot sium bromide.
Zl eI ° JDU ,Zincum Oxidatum, oxide of zinc, i a whit ,
of ,amorphou powder, becoming pale ellow hen hea d,
in oluble in , ater, but oluble in dilute ace ic acid. It wa
108 Zl o IDE.
form r1y named a1 0 Flore zinc " 'hilum albtlm, Lana
ph'lo ophica. For when the metal is melted in open vessels
th 0 idi'e urfac take fire, burns with a dazzling white
fl m, nd ive off den e hite fume. Thi phenomenon
known long ago to Dioscorides, and compared by him to
the form tion of 001. 1
o i e of zinc wa largel u ed formerly in the treatment
of EPILEP y nd other di ea e of a imilar character, especiall
in oung children, in whom opium and morphia are
inadmi ible, It u to be called the br in opiate of
chil hood, Rufel nd reckoned it among the anti-epileptic
specific if given in large do e , and it continued to be used
for long p riod. t the pre ent day oxide of zinc ha
be n uper e d by newer remedie, especially by pota -
ium bromide; but ven at the pre ent time communication
occ ionally ppe r which e tol the effic cy of 0 ide of zinc
a en nti p modic,N t mpt have been made to
e tabli h thi heoretically from the ymptoms produced by
poi onou do ,and from perimental result ,
u tS
I' late that chemi t whil t preparing flowers of
zinc inc utiou ly filled he hole laboratory wi h the fume ,
an e.. perienc d, in con equence, difficulty in breathing,
l' i 0, be d che, leeple ne , p in in the abdomen,
vomi in cou hing, nd h avine of the limb. The
v l' iO'o 1 until he bird da ) and he general eakne
ill he third e k, h n compi te r covery took place.
ibm l' give n ccount of e er 1 e h u tive E PERI-o
H • BIG. The fir t made b Glauber in
I' 165-, he other chi fl b "\ rn ck in the ear
11 of h m e fin en i n the me mp om
ju de crib d. 1'fila a mini t red 0 ide of zinc
i 1
. Pick • Z
63·
im und n tieri ch en
ZI 0 0... IDE. 109
to small and feeble dogs in dose of from 9 to 18 grammes,
with no further result than painles vomiting.l
highly cultivated, powerful man of forty-three
years of age was seized every six or eight weeks
with a violent epileptic fit. The reading of a medical
treatise 51 led him to try oxide of zinc in gradually
increasing doses j he took altogether in five months
195 grammes (3000 grains). t he end of this time, he
wa pale, emaciated, and ment lly dull j he tongue
was heavily furred, the bowels constipated, the abdomen
distended, the legs redematous, the pulse thready and
infrequent, and there was great bodily weakness. There
was no vomiting throughout. During this period there had
been no epileptic attacks. The medicine which had caused
uch disastrous results was topped and the diet carefully
regulated. In a few week the pa ient recovered, but the
redema of the feet and the con tipation continued for some
time longer j the epileptic attacks again returned with the
arne intensity as before.s
This case would be more instructive if oxide of zinc only
had been taken, but being combined with extract of henbane
and oil of chamomile, it merely shows that the amount
mentioned could be taken in five month without producing
PRE T injury. How far this may be due to the other
t-v 0 drug cannot unfortunately be ascertained.
A. ichaelis specially investigated the action of zino
o ·de. He himself took while fa ting as large a dose as 0'36
gramme (5l grain ) j irritation of the tomach amounting to
violent vomiting, and a general en ation of wearine 5, were
he re ult. He admini tered ithin four months 72 gramme
(1000 grain ) of oxide of zinc to a trong dog in its food,
omiting, utter pro ration, trembling of the limb, and
dulne followed, and the animal wa attacked by convul
ion, which recurred daily for three month j it wa
then killed, and gastro-enteriti as found to be pre ent.
I Orfila, CL hrb. der Toxicologie' ueber on Krupp, 1853, Bd. ii,
. 37·
:I iedler, Hufeland' C Journal del' pra . Heilkunde,' I 31, . 65.
• Bu e, C per s C ochen chI'. f. d. e. Heilkunde,' I 37, S. 302.
4 'cha Ii , CArch. fiir physiol. Heilkunde,' I ""I, s. 109.
110 P I 0 OU E:Jj'FEOT OF ZI 0 OXIDE.
On e amin tion the metal wa found in all the organs, and
e pecially in he brain.
The following account i from Botkin's clinic1 at t. Petersbur
. young man had worked for twelve years in a
bronz fa ory, ·po ed to the fume of oxide of zinc;
he graduall dev loped general cachexia, which was characteri
by io] n irritation of the tomach and intestines,
he ache, rigor, and cramp in the leg ; pare i of the
ri ht ide of th face and of the corre ponding extremities
follo ed. The patient tated that he bad left the factory a
month b fore he came to the hospital; the urine, neverth
Ie , till contained zinc. He was afterwards discharged,
materially improved.
In tb zinc mine of ile ia the workmen suffer from
ob tinat catarrh of he air-pa sages and of the intestine,
in con equence of inh ling he fumes or he dust of zinc
o id , and thi i followed by general cachexia. fter
ha in orked in the mine for ten or twelve year they
of n pI' ent 11 the mptom of tabes dorsalis; pains in
the loin , tenderne of he sole of the feet, heat and
pricklin in he Ie , ith diminished en ibility nd nnmbne
in i ola ed po , increa ed excitability of the cutaneous
nd tendon refle e , fe tinating and c1um y gait due to
dimini b d u cuI I' en ibility without atrophy or 10 s of
e1e ric e ci bilit of he mu c1es, and finally a |
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