COLUMBIA LIBRARIES OFFSITE HEALTH SCIENCES STANDARD HX64090108 QP971 .K23 1909 The harmful effects RECAP Kebler ...The harmful effects of acetanilid, antipyrin and Dhenacetin. QP971 K23 1909 THE LIBRARIES iHetrical Hihvavv Digitized by tine Internet Arciiive in 2010 witii funding from Open Knowledge Commons (for the Medical Heritage Library project) http://www.archive.org/details/harmfuleffectsofOOkebl Issued July :i, lleased to publish your letter in the forthcoming bulletin of the Department of Agriculture if it can be used to advantage and if you have no objection. We agree with you that the barm done by acetanilid does not result from its proper use under the direction of the pliysician, but is mainly the result of the i)romiscuous and indiscriminate use of the product by the laity. The (tbject of our investigation is not to conduct a war against acetanilid and similar drugs, as you suggest, but rather to throw safeguards around the public and (bus prevent, as far as possible, a repetition of the many unfortunate accidents wliicli are reported to have resulted from the ill-advised use of these remedies in the past. Much has already been accomplished along this line through the agency of the food and drugs act, which requires that the label of medicinal preparations shall contain information relative to the quantity or proportion of certain ingredients, Avhicli are entmierated in the law, and their derivatives and preparations. By far the greater number of manufacturers have shown a disposition to com- pl}' with the law in declaring the prescribed drugs, but an investi- gation shows that many preparations containing these or other dan- gerous agents Ijear statements which transgress the section of the law on misbranding. The misrepresentation in many instances takes the form of assertions to the effect that the remedy is harmless or tliat it contains no poisonous or harmful ingredients. Again, the public is given to understand in many cases that the medicine can be taken practically ad libitum until the desired effect is obtained. Some of the manufacturers of acetanilid preparations, not content with claiming that their products contain no poisonous or harmful ingredients, go even further and assert that the medicine, in addition to being an efficient remedy, acts as food or nourishment for the up- building of some particular part of the body; that it is, in short, a " nerve food " or a " brain food." With regard to this use of the word " food " the judgt; in the case above referred to in his charge to the jury spoke; as follows: If that word ["itrain food"!, spelled in llie two differeni ways (bat it Is spelled, would fonvey 'o lli<' ordinary citizen llic idea thai it was a food for 8 ACETANILID, ANTIPYRIN, AND PHENACETIN. the brain as contradistinguished from the idea of a food for the whole body, then it is — and I so charge you in this tirst prayer — misleading, and therefore a violation of the law. The information submitted in the following pages with regard to the nmnber of instances quoted in the literature of the subject in which poisoning, death, or habitual use has been known to result from the administration of acetanilid, antipyrin, and acetphenetidin is summarized in section A of the table following. The information as tabulated in section B was furnished by 400 physicians, in reply to letters of inquiry issued by the Department. Nine hundred and twenty-five of these letters were sent out, and 400 replies were received. Granting that the 525 physicians who did not reply had no cases to report, the question may profitably be asked, if 925 physicians have observed 814 cases of poisoning by these drugs, 28 deaths which were attributed to their use, and 136 instances of habitual use, how many such cases have in all probability been ob- served by the 125,000 physicians scattered throughout the United States? The first summary, C, includes both the number of cases recorded in medical literature and those reported by physicians. Cases in which deleterious or fatal effects have been produced by acetanilid, antipyrin, and acetphenetidin. A. CASES RECORDED IN MEDICAL LITERATURE, 1884-1907. Substance. Poison- ing. Deaths. 13 10 3 Habitual use. Acetanilid 297 488 70 32 Antipyrin Acetphenetidin 1 Total 855 26 33 B. DATA REPORTED BY PHYSICIANS. Acetan ilid 014 105 95 16 5 7 112 Antipyrin 7 Acetphenetidin 17 Total 814 28 l;6 C. TOTAL OF COLLATED CASES (A AND B). Acetanilid 911 .593 165 29 15 10 144 7 18 Antipyrin Acetphenetidin General total 1,669 54 169 REPORTS OF PHYSICIANS. 9 REPORTS OF PHYSICIANS WITH REGARD TO PERSONAL EXPERI- ENCE IN THE USE OF ACETANILID, ANTIPYRIN, AND ACET- PHENETIDIN (PHENACETIN). For the purpose of obtaining information with regard to the poisonous eli'ects of acetanilid, antipyrin, and phenacetin from the viewpoint of personal experience and observation, the following letter of inquiry was addressed by the Department of Agriculture to medical practitioners in the United States: United States Department of Agriculture, Bureau of Chemistry, Washington, D. C, June 1, 1908. Dear Sir: We are collecting inforuiatiou relative to the poisonous nature of acetanilid, antipyrin, and phenacetin, and in order to make the data as com- plete as possible I am sendinij; you a number of questions and would ask that you supi)ly the information requested at your earliest convenience. If there is not sutticient space allowed to give all the data you may possess it is expected that you will use the blank pages of the folder, making the statement as concise as possible. The information requested is for the use of the Department in comi)iling a bulletin, and general cretllt will be given for all data supplied. An early reply will be much appreciated. Respectfully, H. W. Wiley, Chief. Following ar*e the questions referred to in this communication, tlie inquiries relating in each instance to the three drugs— acetanilid, antipyrin, and phenacetin: 1. To what extent do you use these drugs in your ])ractice? 2. What dose do you ordinarily i)rescribe for adultsV 3. Do you prescribe them more or less freipiently than formerly? Why? 4. What is your (»i)inion with regard to the relative safety of these three drugs V f). Have you observed instances of acute or chronic poisoning or cyanosis caused by these drugs? How many of each? 0. In what form was the drug administered? 7. About what dates did tiie poisoning occur? 5. Were the patients adults or children? 1>. For what ailment was the drug taken? 10. Was it ordered by a physician? 11. Was it used internally or externally? 12. Quantity taken? I.'J. Give brief history of cases observed by you, omitting details. 14. Have you ol).served any cases of habitual use of any of these drugs or of any jtrepiirations containing them? I.'J. In what form was the drug taken? 16. Were there any ill effects? (Jive? brief description. 17. Were there any protracted ill efl'e<"ts? 18. Give a brief clinical liistory of each case. This lettci' of inquiry was sent (o physicians (Inoughoiil the Fuitcd ►States, (he oljject bcurig to secure inroiinalion which woiihl represent 10 ACETANILID, ANTIPYRIN, AND PHENACETIN. as closely as possible the conditions existing among the people at large, so far as the harmful effects of acetanilid, antipyrin, and phenacetin are concerned. Much information relative to poisoning by these drugs could have been obtained from the records of hospitals, particularly those located in the larger cities, but it was thought that information from this source would not be of a strictly representative character. The conditions aifecting hospital patients differ from those surrounding patients in private homes, and this difference is particularly marked in the case of the drugs under consideration. For this reason it was deemed advisable to secure the desired informa- tion from physicians at large rather than from hospital records. Four hundred replies were received to the 925 letters sent out, and the information submitted is set forth in the following pages. Question 1. — To what Extent do you Use these Drugs (Acetanilid, Anti- pyrin, Phenacetin) in your Practice? Extent of use. Frequently Moderately Oceasionaily Rarely Only in pertussis . Externally Never Total number of observers Number of replies. Acetanilid. Antipyrin. Phenacetin, 90 30 62 100 6 112 9 11 61 99 14 8 208 109 38 73 94 400 From this it would appear that acetanilid is used frequently or moderately by 120, or 30 per cent, of the physicians; antipyrin by only 20, or 5 per cent; and phenacetin by 147, or 36.7 per cent. On the other hand, 112, or 28 per cent, of the physicians state that they do not use acetanilid at all ; and 100, or 25 per cent, use it but rarely ; 208, or 52 per cent, never use antipyrin, and 90, or 25 per cent, use it but rarely ; 94, or 23.5 per cent, of observers never use phenacetin ; and 8G, or' 21.5 per cent, employ it but rarely. Thus, of the three drugs phenacetin appears to be most used by physicians, with acetanilid second, while antipyrin is apparently used to a much less extent than either of the others, only 5 per cent of the physicians stating that they employ it frequently or moderately. The reason for the more extensive use of phenacetin is undoubtedly to be found in the fact that it is generally regarded as being the least harm- ful of these agents. This was indicated particularly in the answers to question No. 4. EEPORTS OF PHYSICIANS. 11 Question 2. — What Dose do you Ordinarily Prescribe for Adults? Acetanilid. Antipyrin. Phenacetin. Dose. Number of ob- .servers. Dose. Number of ob- servers. Dose. Number of ob- servers. Grains. 0.5 1 2 1 1 2 7 2 1 25 15 9 19 1 18 9 32 3 2 39 2 1 9 6 1 1 38 3 6 12 1 1 2 1 1 Grains. 0.5to2.5 1 1 2 1 1 1 2 3 5 4 3 15 1 1 1 1 1 1 25 8 26 5 5 8 2 1 ir, 1 2 2 1 1 1 1 Grains. 5 to 6 1 0.5 to 1 1 1 1 0.5 to 10 1 to2 1 to 2 1 I 1 to 10 1 to 2 5. . ] 1 to 2 1.5 1 to 6 •> 1 to 3 2 1.5 to 2.5 ■I 1 to 5 2 to 3 2 10 l.f) 2 to 4 2 to 3 13 2 to 5 2 to 4 2 to 3 2.5 3... . 2 to 6 :il 2 to 4 . 2 to 6 2 to 7 5 1 2 to 5 3 to 5 1 2 to 7. 5 3 to 10 2 to 10 . 1 2.5 3 to 15 2 to 20 1 2 5 to 3 3.5 4 2 5 ]('> 3 2 5 to 7 5 1 3to3.5 4 to 5 3 4 3 to 4 4 to 6 27 3 to 5 5 3 to 6 2 3to 6 5 to 7.5 3 to 8 3 3 to 7.5 5 to 10 . . 3 to 15 1 3.5 5 to 15 4 3 4 7.5 4 to 5 2 4 to 8 4 4t<^)12 S 5 S7 5 8 to 10 . . 5 to 6 ... 6 to 7 5 1 10 14 5 to 8 10 to 12 5 5 to S . . 2 5 to 10 ... 10 to 15 . 6tol0 5 to 15 G 7 to 8 35 fi tolO 10 to 20 12 to 15 . 3 7 2 7 5 12 5 1 7.5 to 10. 15 7 to 10 2 10 Up to 20 7.5 1 s 2 8 to 10 1 10 10 to 12 7 1 10 to 20 2 SUMMARY. .NiiiiilMT statinp dose .. .Number wbo 94 From this it would appear that out of 274 observers who stated that they use aeetauilid IT, or 0.2 j)er cent, empk)y less than 2 f^rains as a mininiiiin dose for adults; 113, or 41.2 per cent, employ 2.5 j^ains or less as a minimum dose; and 155, or 5(5.5 per cent, employ from 3 to 5 grains as a minimum dose. Two hundred and forty, or a little over 87.5 per cent, never exceed a dose of 5 grains, and 34, or not quite 12.5 per cent, employ doses exceeding 5 grains. With regard to antipyrin only 23, or 15.3 per cent of the 150 .l>s("rvers who stated that they use this di-ug, exceed a dose of 10 grains, while 00, or 44 per cent, never exceed a dose of 5 grains; 12 ACETANILID, ANTIPYEIN, AND PHENACETIN. and 109, or 72.6 per cent, employ 5 grains or less as a minimum dose. Out of 297 observers using phenacetin 10, or 3.3 per cent, employ less than 2 grains as a minimum dose; 90, or 30.3 per cent, employ 2.5 grains or less as a minimum dose; 188, or 63.3 per cent, employ from 3 to 5 grains as a minimum dose ; 89, or 29.9 per cent, use doses exceeding 5 grains; while 208, or 70 per cent, never exceed a dose of 5 grains. From this it seems reasonable to conclude that the doses of these remedies which are prescribed to-day are much smaller than those which were formerly employed. The report of the therapeutic committee of the British Medical Association with regard to the ill effects of acetanilid, antipyrin, and phenacetin, published in 1891, a summarj^ of which appears on page 20, made a deep impression on the medical mind, and undoubtedly did much to bring about a more conservative use of these drugs, particularly so far as dosage is concerned. The committee concluded from its investigation that the ill effects which had been ascribed to these remedies were very largely the direct result of injudicious and excessive dosage, and in harmony with this conclusion they suggested that they should be used with greater caution in the future. Since that time the doses employed have been smaller than before, and it has been noted that coincidentally with this change the number of accidents resulting from the ingestion of these remedies has fallen off to a remarkable extent. A point of interest in connection with the subject of dosage and frequency of administration was brought out in a recent trial, wliich involved the misbranding of a certain headache remedy con- taining among other ingredients acetanilid and antipyrin. The evi- dence presented showed that the directions for use accompanying many of these acetanilid preparations are not sufficiently definite to safeguard the consumer against a too frequent repetition of the dose, and, in fact, that manj^ of them advised a rejDetition of the dose until the desired result should be obtained. An examination of a number of prescriptions for adults on file in various pharmacies in Wash- ington, D. C, brought into court as evidence, supplied the following- information on these points: (1) The average dose of acetanilid pre- scribed was 2.43 gTains, and of phenacetin 1.92 grains; (2) the average interval between doses was, in case of the two remedies, 3.03 hours. REPORTS OF PHYSICIANS. 13 Question 3. — Do you ruKscKiiiE Thkm moke ou j.kss FKiXiUKNTLV than Fok- merlyV WhyV Less frequently More frecuR'iitly To sjime i-xtent Totiil iitimber answering this tiiicstioii Total number not answering this (jiiestion Number of observers for — Acetanilid. 179 13 79 271 129 Antipyrin. 135 265 Phenace- tin. 143 4(i 90 279 121 From these fi<2:iu-es it -woiikl app-^^ar that acetanilid is used less frequently than formerly by OG per cent of the observers, antipyrin by G5.9 per cent, and phenacetin by 51.2 per cent. Acetanilid is emj^loyed to about the same extent as formerly by 21). 1 per cent, antipyrin by 31.1 per cent, and phenacetin by 32.2 per cent of ob- servers. Only 4.7 per cent use acetanilid and 1(').4 per cent use phenacetin more frecpiently than formerly. The reasons given for the less frequent use of these drugs are in most instances their toxicity and particularly their depressing effects. (H'KSTioN 4. — What i.s Your Otinion with Rkgakd to thk Kklative Safety of THESE DUUGSV P'ifty-eight observers replied that acetanilid was the least danger- ous, 18 named antipyrin, and 231 named phenacetin. Thirty-seven, or over 10 per cent, stated that in their opinion there is but little differ- ence between the tliree as far as toxicity is concerned, one being about as powerful a depressant as the others. P"ifty-six did not reply to this (jiiestion. The figures indicate that phenacetin is regarded as the least dangerous of these three agents l)y 231 out of 344 observers, or G7.4 per cent; acetanilid by 58 observers, or 1G.8 per cent; and antipyrin l)y 18, or 5.2 per cent. Question 5. — Have you Observed Instances of Acute or Chronic I'oisonin*; OK Cyanosis Caused by these Drugs? How Many of EachV EflectH profliiccd. ADULTS. A<-Mtoi>onin)f (■yaniwis Acute, fatal Total number of cwwn reported r IIII.DKKS. Acute |>oi.>4onin(; ( 'yHiioHix Acute, fatal Total number of caMcw reported Total number of cattes, udultji und cliildren 7 Number of cases. Aeetjinilid. 2«4 12 213 10 Antipyrin. I'henaer •tin. 69 4H 2 14 4 • 28 .519 H7 H 54 4 7 17 10 1 1 Ofi IH 11 fil4 lO,') n 14 ACETANILID, ANTIPYRIN, AND PHENACETIN. Out of 288 i:)ractitioners who submitted an answer to this question in regard to acetanilid, 219, or 76 per cent, stated that they had ob- served instances of poisoning following the use of this drug. These 219 observers report 614 cases of poisoning, including 17 deaths. Eighty-nine, or 46.3 per cent, of the 192 physicians who submitted similar information with regard to antipyrin stated that they had observed toxic effects and reported 105 cases, including 5 deaths. Of 306 physicians who submitted data on phenacetin, 66, or 21.5 per cent, reported 95 cases of poisoning, including 7 deaths. Of the 614 cases of poisoning which are said to have resulted from the ingestion of acetanilid, 17, or 2.7 per cent, terminated fatally; of the 105 cases of antipyrin poisoning, 5, or 4.7 per cent, resulted fa- tally; and of the 95 cases of poisoning by phenacetin, 7, or 7.3 per cent, terminated fatally. Additional information with regard to the fatal cases follows : ACETANILID. Pueumonia (child) One-lialf grain every two lionrs until 2 grains were taken. Capillary broncliitis (child)-- Small doses frequently repeated. Capillary bronchitis (child) Small doses frequently repeated. Typhoid Five grains every four hours. Headache About 20 grains. Headache Thirty grains (?) Headache "Orangeine" taken freely. Headache Thirteen or fourteen 5-grain doses in twelve hours. Headache Bromo-seltzer. Neuralgia Dose not given. Neuralgia of heart Five 5-grain doses in five hours. Burn Boroacetanilid applied freely. Burn (infant) Acetanilid applied freely to umbilical cord. Headache Excessive dose of " bromo-seltzer." Typhoid (child) Five grains. Typhoid (child) Doseuot given. Malaria (child) One and one-half grains. ANTIPYRIN. Pneumonia Ten grains every two to three hours. Death on third day. Fever (child) Twenty grains. Death in two hours. Acute rheumatism Antipyrin dispensed instead of "Aspirin." Quan- tity not stated. Patient died suddenly. Headache- Ten grains, followed by 15 grains in an hour. Neuralgia Five grains every three to four hours. One drachm taken in two days. REPORTS OF PHYSICIANS. 15 PHENACETIN. I'ueniuouia Seventy grains daily for two days; died suddenly. Influenza Five grains every three liours; not over G doses. Broucliitis (1 year) Two grains every three hours; five doses; died twelve hours after last dose. Typhoid Two and one-half grains every two hours until 1 scruple was taken. Headache. Ten grains. Headache (cerebral tumor) Fifteen grains in twelve liours. Woman, aged TO Two 3-grain doses two hours apart. Question G. — In What Form was the Drug Administered? [In cases of poisoniug.] Form. Powder Tablets EiJls In solution Form not stated Number of cases. Acetanilid. 425 1(;3 6 4 ii; Antipyrin. I'henace- tiu. The form in which the drug was administered in the cases of i)ois- oning above mentioned is set forth in the accompanying table. Pro- prietary preparations containing acetanilid were reported to have been used in 77 or 12.5 per cent of the cases. Question 7.-^xVbout What Dates did the I'oisonino Occur? Number of cases. Year. Number of cases. Year. Acet2 2 2 1905 5 IS93 1906 1 3 1 1S94 3 7 3 f) 3 2 1907 7 1S93 2 1 1908 3 1896 No dalt! fe'iveii Total... 55 1897 52 1X98 5 Gil 105 lM'.t9 95 1900 1 Question 8. — WEKE the I'AliKNTS ADI'I. IS ou ( 'lIll.ltltKN? Af,"- if |pali<-iil. Number of cfwes. Ae«s than 10 . . . Kxt«Tnal ca>es Fatal cases".. . DoM: not stated Total . . . . 5 1 3to6 1 5 1 8 to 10 3 10 1 1 Dose not stated 10 Total 18 ' See pnge 14. 82.'il0— P.iill. 120— (»;» 18 ACETANILID, ANTIPYRIN, AND PHENACETIN. Out of the 368 cases in which the dose of acetanilid administered to adults was stated, the poisoning was caused by doses of 5 grains or more in 331, or 89.9 per cent; with antipyrin the ill effects were caused by doses of 10 grains or more in 89.T per cent of the cases. while with phenacetin the toxic effects were caused by doses of 10 grains or more in G7.8 per cent of the cases, and by doses of 5 grains or more in 93.2 per cent of the cases. In 85.7 per cent of the cases the poisonous effects of acetanilid ad- ministered to children were caused by doses of 2 grains or more ; with antipyrin the ill effects were due to doses of 3 grains or more in 85.7 per cent of the cases, while with phenacetin no ill effects were re- ported to have resulted from doses under 2 grains. Question 13. — Give Brief History of Cases Observed by You, Omitting Details. The information submitted in answer to this inquiry is given in connection with the replies to the remaining questions. Question 14. — Have You Observed Any Cases of Habitual Use of Any of These Drugs or of Any Preparation Containing Them? An endeavor was made to obtain information with regard to the extent to which these drugs are used habitually, as it has long been known that acetanilid, antipyrin, and phenacetin are habit-forming drugs, particularly acetanilid. The habit is acquired in most in- stances through the use of the remedy without the supervision of the physician for the relief of minor aches and pains, especially headache. These affections are usually of a recurrent character and, the remedy exerting but a palliative effect, the dose after a time must be repeated and in time the patient may become dependent on the drug. Further- more, the prolonged or habitual use of these agents tends to produce an impaired condition of the general health w^hich, as in all such cases, is accompanied by a lessened resistance on the part of the body to disease. Under these circumstances the affection for which the remedy was originally taken assumes greater proportions than ever, and as a result there is additional call for the drug. Thus a vicious circle is established — more drug, imj^aired bodily health, lessened resistance, more pain, more drug. It has been said that in its baneful effects on the system and in the difficulty which is experienced in giving up the use of these drugs in many instances, the habit ranks as an evil with the opium habit. Whether this is true or not, there can be no reasonable doubt that their prolonged or habitual use is decidedly harmful to the sys- tem. In spite of this fact, the habitual use of these agents is spread- ing among the people and it is becoming more and more apparent EEPORTS OF PHYSICIANS. 19 that an eH'ort should be made to acquaint the general public with the ill effects which may reasonably be expected to follow such use. In rei)ly to the inquiry by the Department, 112 instances of the acetanilid habit were reported, 7 of the antipyrin habit, and 17 of the phenacetin habit. It should be remembered, however, that neither these cases nor those which are recorded in medical literature give an adecpiate indication of the extent to which these drugs are used habitually, inasmuch as onl}' those cases have been reported in which the ill effects were so marked as to call for the services of a ph^'sician. Interesting information with regard to the habitual use of these drugs can be obtained, by consulting the original reports of the cases re- corded in medical literature. Question 15. — In what Form was thic Drug Taken"? llu tilt' case of habitual users.] « Number of cases. Form— Acetani- lid. Anti- pyrin. I'heiiac- etin. I'owdcrs . 29 25 7 12 Tablets 4 In solution 1 50 8 Fonn not stated Total 112 1 7 17 From this it appears that proprietary preparations were used in at least 50, or 14.G per cent, of the 112 instances of the habitual use of acetanilid. Question l(i. — Were Thp:re Any III Effects V (Jive Description. The number of cases in which ill effects were observed from the use of acetanilid was 8'), from antij)vrin 2, and from ])heiiacetin 7. The chief symptoms observed from the habitual use of these drugs may be briefly classified as follows: Nervous depression, 44 cases; cyanosis, 27 cases; anemia, 15 cases; cardiac depression, 18 cases; dyspnea on exertion, 8 cases; insouinia, 4 cases; constipation, 3 cases; loss of memory, 3 cases; icterus, 1 case; muscular twitchings, 1 case; loss of sexual power, 1 case; edema, 2 cases, and increased headache, 2 ca.ses. Question 17. — Were There Any I'rotracted Ile EfkecisV The replies submitted in answer to tliis question show (hat ]iro- tracted ill effects were ob.served in the case of acetanilid in 38 in- stances, with antipyrin in 2 instances, and with |)henacetin in 5 in- .stances. The (rhroni(; symptoms most often nolecl were anemia, gen- eral debility, nervousness, and weak and irregular heart action. 20 ACETANILID, ANTIPYKIN, AND PHENACETIN. Question IS. — Give a Bkief Clinical History of Each Case. The information submitted in answer to this question is embodied in the data presented in tlie preceding pages. AN INQUIRY REGARDING THE IMPORTANCE OF ILL EFFECTS OF THESE AGENTS, CONDUCTED BY THE BRITISH MEDICAL ASSO- CIATION. In 1894 a committee of the British Medical Association known as the " therapeutic committee," of which Dr. D. J. Leech was chair- man and Dr. William Hunter honorary secretary, conducted an in- quiry with regard to " The importance of the ill effects which occa- sionally attend the use of the three chief antipyretic and analgesic agents, phenazone (antipyrine), acetanilide (antifebrin) and phen- acetin." For the purpose of this investigation a letter of inquiry was sent to medical practitioners in Great Britain requesting infor- mation based on j^ersonal experience with these drugs. The replies received in answer to this letter furnished much valuable information and the report of the committee * contained descriptions of a number of cases of poisoning. The following summaries are taken from the report of the committee, and contain information with regard to the principal effects noted by the different observers. Ill effects from the administration of acetanilid, antipyrin, and phenacetin, as observed in Great Britain. [When the actual dose which occasioned the ill effect is not stated, employed by the observer is given within parentheses.] the usual dose Nature of ill effects. Grains administered. ACETANILID. Alarming collapse more than once Excessive sweating, cyanosis, feebleness of pulse, and partial collapse, comparatively frequent Cyanosis after repeated doses Cyanosis on two occasions Cyanosis and collapse, once after a double dose Collapse in two children Cyanosis and collapse In one or two cases Cyanosis and depression Do Cyanosis Collapse and death Collapse after continuous doses of 7^ grains Collapse after 10 grains ^ Undue perspiration and depression Do Collapse Depression Palpitation and collapse Severe cyanosis after 2 doses of 10 grains each Cyanosis once Cyanosis, profuse perspiration, and partial collapse. Cyanosis and collapse Do Do ; Do Collapse in phthisis even after 2 grains Alarming collapse in a child by a second dose (4). (2 to 5). (5 to 10). 7 every 4 hours. (10). (6 to 10). Not stated. {^). (10). 7i. Not stated. (5 to 10). (2 to 3). (5). (8). (8 to 10). (6 to 8). (2 to 20). (5 to 8). (4 to 8). (10). (8 to 10). (3 to 10). (5 to 10). (8 to 10). 2. 3. "Brit. Med. J., London, 1894, 1: 85. LITERATURE ON ACETANILID POISONING. 21 III effects from the administration of acetanilid, etc. — Continued. Nature of ill effects. Grains administered. ANTIFVRIN. Weakness and shakiness Serious collapse in a case of typhoid fever Syncopal attack on one occasion Symptoms of collapse Enfeebling in its action Depres.san t Do Cardiac weakness and Irregularity Great dejjression Great depression and exhaustion Alarming depression Cyanosis and dangerous cardiac depres-sion Do Depressant on heart E.xcessive sweating, cyanosis, and partial collapse Vasomotor pains, lividity. jirofnse perspiration, tendency to collapse and to pnenmiinic congestion Cdllnpse and death in a case of rheumatic fever Ahirmiiig faintiiess in anemic individuals Languor and depression Weakening effect in 10 fier cent of ca.ses Serious cdllapse in a case of typhoid Los-sof speech, lasting 24 hours, in a case of commencing meningitis which subsenuently proved fatal .\. condition of mania from long-continued use of the drug, recovered from when drug was withheld Dyspnea and much nervous excitement once out of many hundreds of <-ases Salivation with urticarial rash twice in same patient Dizziness and loss of power in legs PHENACETIN. Collapse on one occa.«ion Extreme weakness, cyano.sis, and feebleness of pulse Cyanosis once Slight giddiness once Depression, although not often Lividity and diaphoresis Subnormal temperature, coldness, shivering (20 to 40). 30 twice. 1.5. '20. (.5 to 20). (12 to 20). (20). 1^ every 4 hours. 30 at hourly intervals. 1.5 every 4 hours. 4.5 in 8 hours. 20. 20. (15 to 20). (20). (30). KO in 5 hours. (15 to 20). (15). 20. repeated in an hour. 2 (loses of 30. 7. 5, repeated in an hour. 5 every 3 hours for 3 days. (10 to 15 every 4 hours.) 7 every 4 hours for 3 days. (5 to 10). (5 to 10). (10 to 20). (5 every 4 hours). LITERATURE ON POISONING BY ACETANILID, ANTIPYRIN, AND ACETPHENETIDIN (PHENACETIN). ACETANILID. I NTRODITC'TOR V R KSIT M E, The' followinfj l>il)liograpliy contains references to the rocorderl cases of poisoning by acetanilid and preparations containing it, from the date of its introthiction as a medicine in 1880 to the end of the year 1007, together with a brief abstract of each case. It was found (o be diflicult in some cases to draw the line between cases of actual j)oisoning and cases in which the symptoms were hardly severe enough to justify the use of the word "toxic" in describing them. The word " poisoning" as used in the subsequent pages is inleiuled to include all cases in which unexpected, undesired, and deleterious ef- fects resulted from the ingestion of acetanilid. Thus (he recorded eases in which cyanosis was the only untoward symptom observed were included in this report, inasmuch as the cyanosis was an iine.K- jH'cted and undesired efl'eel of (he ingest ion of (he diiig in each case and u manifestation of its harmful n. ''A CISC of ;i(<-l:iiiiiid poisoning. I'Jiil.idclplii.i I'olyi-lynic, 1S!)7, <>: IWl. 24 ACETANILID, ANTIPYRIN, AND PHENACETIN. of collapse appeared. The ointuieot was discontinued and the symptoms gradu- ally disappeared. The symptom which appears most frequently in the recorded cases of poisoning by acetanilid is cyanosis. With but very few exceptions it is a constant symptom, the depth of the discoloration ranging from a mere dusky hue of the skin or mucous membrane to a color which is described as " blackish-blue " or even " black." This symptom was observed from the first and even in Cahn and Hepp's original article, which marked the advent of acetanilid in the world of medicine, cyanosis is casually mentioned as a side effect of the administration of the drug. At that time but little significance was attached to its occurrence. We now know, however, that it is an exceedingly un- desirable symptom, inasmuch as it is due to a deterioration in the quality of the blood caused directly by the presence of decomposition products of acetanilid. Accompanying the cyanosis there was ob- served in most of the cases prostration, which varied in degree from mere depression of the bodily functions to actual collapse. In addition to these symptoms there w^ere obserA^ed in many instances vertigo, faintness, liviclity of the face, a pinched and anxious expression, dyspnea, excessive restlessness, increased perspi- ration, coldness of the extremities, rapid and feeble heart action, and in severe cases, stupor or coma. The occurrence of an eruption on the skin is mentioned in only a very few of the recorded cases. This is also true of disturbances of vision and of the functions of the kidneys. The habitual use of acetanilid is specifically mentioned in 32, or 10.7 per cent, of the recorded cases of poisoning. This gives no conclu- sive information, however, as to the actual extent of the acetanilid habit, inasmuch as only those instances of habitual use are recorded in which the ill effects were probably so severe as to cause the patient to seek the advice of a physician. A consideration of the relative number of cases occurring in different years is of value, however, and shows a marked increase in the number of cases of habitual use during recent years, as indicated in the following table : Cases- of hahitual use of acetanilid reported, 1800-1907. [No cases roported for the years omitted.] Year. 1890 1S94 1896 1899 1900 1902 Percent- age of to- Number tal num- of cases ber of reported. cases of habitual use. 1 3.12 2 6.24 2 6.24 1 3.12 1 3.12 1 3.12 Year. 1903 1905 1906 1907 Total Number of cases reported. Percent- age of to- tal num- ber of cases of habitual 12.50 15.60 40.62 6.24 LITERATURE ON ACETANILID POISONING. 25 The increasing u.se of proprietary remedies containing acetanilid since the year 1001 is indicated in the published reports, as follows: Cases in irhicli the patient is reported to have taken a proprietary preparation, 1891-1907. [No cases reported for the years omitted.] Year. Number of cases reported. 1 1 3 Percent- age for each year. Year. Number of cases reported. Percent- age for each year. 1891 3.7 3.4 10.3 17.2 1906 12 7 41.3 1895 1907 24.1 1896 Total 1905 29 ' The use of proprietary preparations containing acetanilid is not mentioned in the reports of cases published during the eight years preceding the year 1905, but in the reports published during 1905 the use of these preparations is indicated in 55.5 per cent of cases. In 1906 the use of these preparations is indicated in 63.1 per cent of the recorded cases, and in 1907 in 87.5 per cent. It is interesting to note that accompanying this rapid increase in the use of proprietary acetanilid preparations during recent years, which indicates a more indiscriminate use of acetanilid by the general public, there has been an increase in the total number of cases of poisoning reported, in the number of fatalities, and in the number of instances of habitual use. In this connection a comparison of the four preceding tables is of interest. ABSTRACTS OF ACETANILID CASES. 188G. Bebnheim. L'antifi'brini'. Kov. iiu'-d. de Test, Nancy, ISSG, 18: 099. Oiic-lialf of the patients takinfx acetanilid liad cyanosis of the face and extremities; .'j.Tn j^raius ^civen to a child prodnced chills and collapse. Three patients had a chill when the tcniporatnre he^'an to rise a.i,'aiii. Cahn, a., nnd IIum'. ]'. Das Antifclirin, ein nenes Fichci-iiiillcl. Centrlil. kiln. .Med., Leipzif,', ISSO, 7: HCl. Cyanosis of the face and extremities, varying; in intensity, was tiie only perplexing; symptoiu observed dnrin^x tlie adniinisti'al ion r)f acetanilid. i:iSKMi,\i!T. n. I',eohii(litnn;.'cii iiher das Antifclirin. .Miincli. mod. Wdclicnsclir., ISSO, »:{: S.-.I. Itifreslion of acetanilid was followed by the ;ippear:ince of a paiinlar ernption coverinK tlie etitin; l)ody. Kkik<.i,I'.. ('•. Antifebrin ( Acelanilin ) als Antifebrile nnd Aid iseptii-nni. Cen- trl»l. lilin. M(!d., Leip/JK, bSStJ, 7: 7<;]. Cyanosis of tlje dieeivS and visible inncons nicinbranes was the only ill effect obHerved durhig the administratir)n of acetanilid. 26 ACETANILID, ANTIPYRIN, AND PHENACETIN. Lepine, R. Sur I'action cle I'acetanilide (autifebrine). Semaine nied., Paris, 1886,' 6: 473. Doses of more than 7.5 grains of acetanilicl, continued for several days, caused cyanosis of tlie face and extremities. MouissET. Note sur Temploi de I'acetanilide dans le traitement de la fievre typhoide. Lyon med., 1886, 53: 309. Three out of seven cases of typhoid, treated with acetanilid in doses of 7.5 grains, presented symptoms of cyanosis. RiESE, H. Zur Wirkung des Antifebrin. Deutsche med. Wochenschr., Berlin, 1886, 12: 835. Cyanosis of the face and extremities appeared in several cases, particu- larly in phthisis, following the use of acetanilid. In two cases of pneu- monia and one of typhoid the pulse became weak and irregular. Collapse occurred after a single dose of 11.5 grains of acetanilid in a case of phthisis. 1887'. Bauer, F. M. The dangers of antifebrin. Therap. Gaz., Detroit, 1887 (3), 3: 788. Author had several times seen cyanosis produced in women by three or four doses of 3.75 grains of acetanilid. Biro, E. Az acetanilid (antifebrin) hatasarol. Gyogyaszat, Budapest, 1887, 27: 217. (Transl. Abs., Pest, med.-chir. Presse, Budapest, 1887, 23: 446.) (1) Ingestion of 7.5 grains of acetanilid was followed by a severe rigor and an irregular, small pulse. (2) After 'taking acetanilid for eleven days the patient presented the same symptoms as in case 1, and, in addition, clonic convulsions of the lower extremities. BoROSNYoi, L. Az antifebrin mint eskorellenes szer. Orvosi hetil., Budapest, 1887, 31: 1663. (Transl. Abs., Pest, med.-chir, Presse, Budapest, 1888, 24: 103.) Author observed cyanosis in all cases of epilepsy treated with large doses of acetanilid. BouLTON, p. Antifebrin. Brit. Med. J., London, 1887, 1 : 761. On two occasions marked prostration followed the administration of 15- grain doses of acetanilid to feeble patients. Cauldwell, C. M. Antifebrin in the treatment of phthisis. Med. Rec. New York, 1887, 31: 426. Cyanosis of the lips and finger nails was noted in 2 cases out of 30 treated with acetanilid, in 7 to ]0-grain doses. Demikville, p. De I'antifebrine comme nervin. Rev. med. de la Suisse Rom Geneve, 1887, 7: 305. (1) In an alcoholic epileptic, 51 years of age, 7.5 grains of acetanilid three or four times a day caused delirium and hallucinations. (2) Several 15-grain doses of acetanilid caused lachrymation and a prickling sensation about the eyes. Doll. Mittheilungen aus der Praxis. Deutsche Med.-Ztg., Berlin, 1887, 8: 817. Ingestion of 25 pfennigs' worth of acetanilid, about 1.5 tablespoonfnls, in two portions in close succession was followed in about three hours by vomiting, syncope, and collapse. LITERATURE ON ACETANILID POISONING, 27 DrJARDiN-REArMETZ. De racvtanilide conime niMicniiuMit sedatif (In systOine nerveiix. Bill. gen. tberai). (etc.), Paris, 1887, 112: 241. Antlior had observed cyanosis following the administration of doses of 7.5 grains of acetauilid in febrile cases, particularly in typhoid. DuLACSKA, G. Az acetanilid hatasarol. Gyogytiszat, Budapest, 1887, 27: 103. Transl. Abs., Pest, med.-chir. Presse, Budapest, 1887, 23: 444. Two .3-grain doses of acetanilid at two-hour intervals caused epistaxis in one case and profuse uterine hemorrhage in another. After taking acetanilid a phthisic:)] patient became drowsy and the lips showed moderate cyanosis. In all cases the ingestion of the drug was followed by marked prostration. Editorial. Antipyrin and antifebrin. New Orleans Med. and Surg. J., 1887, 15 (1) : 50. A patient with remittent fever took 7.5 grains of acetanilid every hour until 0.5 drachm was taken. The temjierature fell to 95° and the patient became almost pulseless. EiSExnART. II. Beoliachtungen fiber das Antifebrin. Miinch. mod. Wochenschr., 1887, U: 448. A 1.5-grain dose of acetanilid produced cyanosis, and smaller doses caused a mild bluish discoloration of the face. The ingestion of 4 drachms of acet- anilid within six days in a case of rheumatism was followed by the develop- ment of a morbilliform eruption. Faube, .J. L. Notes sur les effets de Tacetanilide dans le traitement de "epilepsia. Compt. rend. soc. biol., Paris, 1887 (8), 4: 401. The administration of from 7.5 to 37.5 grains of acetanilid daily caused well-marked cyanosis. Fattst, W. rel)er Antifebrin. Deutsche med. Wochenschr., IjCipzig and Ber- lin, 18S7, 13: 358. Two doses of 7.5 grains of acetanilid reduced the temi^erature to 94.2° without'symptoms of collapse. Fischer, (i. Antifebrin gegen lancinirende Schmerzen. IMiinch. med. Wochenschr., 1SS7, 34: 42.'"). In 2 c.-ises out of 10 cyanosis followed the admiMislraUon of 7.5 to 22.5 grains of acetanilid. (Jor.orsriiEW. Discussion of paper liy Ansserow on "Antifebrin. Antipyrin, mid 'I'liallin a is Mittel ziir Keguiining des Wiii-iiievcilnstt's lie! Fiebernden." Deuts<-be med.-Ztg.. P.erlin, 1.S.S7. H: 2;{4. Ingestion of 4.5 grains of acetiiiiilid caused collaijse. GiTTMANN. (i. Antifebrin. in seine?' iiiannigfaltigen \VirI. I'.ei'l. kiin. Wochenschr., 1SS7. 24: 942. Ill 4 nut of 248 cases lln' ingcslioii of acetanilid was fr)llowed by cyanosis of the lips and cheeks, (lis.ippe.iriiig within an Iioiir. IIaims. C. Antifebrin. P.rit. Med. .]., [.oiidon, 1.SS7. 1: 12.5.3. The adiiiiiiistr'atioii (if I grains of .'icet;milld (o :i sen riel- fever palieiil S years of age was followed by a rapid fall nf lem|ier;it iire and coll.ipse. 28 ACETANILID, ANTIPYEIN, AND PHENACETIN. Heinzelmann, H. Zur Casiiistik der Antifebrinbehandlung, Munch, med. Wocheusclir., 1SS7, 34: 36. Ingestion of 3.75 grains of acetanilid was followed in one case by dilation of tlie pupils, in another by chilliness and profuse perspiration, and in still another by weakness of the pulse. In a fourth case partial deafness and headache followed the ingestion of 7.5 grains of the drug. Heusler, E. Das Antifebrin. Allg. med. Centr.-Ztg., Berlin, 1887, 56:1074. In 50 cases of typhoid and pneumonia treated with acetanilid, cyanosis occurred in one instance. Average dose, 3.75 grains every six hours. HuBER, A. Ueber Antifebrin. Cor.-Bl. f. schweiz. Aerzte, Basel, 1887, 17:2. Typhoid. Ingestion of 7.5 grains of acetanilid daily for two days was followed by a papular rash especially marked on the forehead, forearms, and hands. Author had also observed instances in which cyanosis and col- lapse followed the ingestion of acetanilid. Jacob, A. Etude cliuique sur I'antifebrine on acetanilide. Nancy, 1887. In 72 cases, cyanosis was observed in 12 instances following the ingestion of 3.75 to 7.5 grains of acetanilid. Collapse occurred in 2 instances after the ingestion of acetanilid by typhoid-fever patieuts ; once after the ad- ministration of 7.5 grains, and again after 3.75 grains. In a case of hemi- plegia, a dose of half a drachm was followed by intoxication and nausea lasting four hours. Three and three-fourths grains produced syncope in case of a tubercular patient. JuNKERMANN, F. A. Antifebrin als Febrifugum und Nervinum. Wiirzburg, 1887. In erysipelas, cyanosis was observed to follow the ingestion of doses of 7.5 grains of acetanilid. MacMullen. J. C. On the action of acetanilide. Australas. INIed. Gaz., Sydney, 1886-7, 6:269. In at least three cases, a condition closely resembling collapse followed the ingestion of acetanilid. Matusofszky, A. ITeber den Heilwert des Antifebrin. Orvos-termeszettud. Ertesito. Kolozsvar, 1887. No. 1. (Transl. Abs., Pest, med.-chir. Presse, Budapest, 1887, 23: 466.) (1) Cyanosis occurred in a case of phthisis after the ingestion of 0.75 grain of acetanilid four to five times a day. (2) Typhoid. Four doses of acetanilid, 6 grains each, every half hour causes cyanosis and collapse. MiJLLER, J. Meeting of Soc. de med. de Strasbourg, Jan. 0, 1887. Gaz. med. de Strasbourg, 1887, 46: 35. Administration of 7.5 grains of acetanilid to a patient with erysipelas 9 years of age caused intense cyanosis of the face. Pavai-Vajna, G. Ueber die Wirkung des Acetanilid Oder Antifebrin. Centrbl. gesam. Therap., Wien, 1887, 5: 481. (1) Man, 25, phthisis: Fifteen grains of acetanilid caused cyanosis and collapse. (2) Man, 28, typhoid: Three and three-fourths grains caused cyanosis. (3) Man, 27, pneumonia : Three doses of 3.75 grains at hourly intervals caused profuse perspiration and cyanosis. LITERATURE ON ACETANILID POISONING. 29 Salm, a. I'eber Autifebriu a Is Antiepilepticum. Neurol. Ceutrbl. Leipzig, 1887, 6: 241. Nearly all of 11 epileptic patients treated with acetanilid, 15 to 45 grains a day, presented cyanosis and a dark discoloration of the urine. ScHTscHERBAKow. I'ebcr den Gebranch von Antifebrin und Naphtha bei Schwindsiichtigen. Deutsche med. Ztg., Berlin, 1887, 8: 234. Acetanilid given by inhalation produced collapse in several cases. Secbetan, L. Note sur I'antifebrine. Rev. med. de la Suisse Rom., Geneve, 1887, 7: 36. (1) Rheumatism: Collapse followed the second dose of 7.5 grains of acetanilid. (2) Tuberculosis: Collapse followed a single dose of 7.5 grains of acetanilid. Seiffp^jt. E. V. A. leiter Antifebrin und seine Anwendung beim akuten Gelenk- rheumatisnui.s. Berlin, 1887. Youth. IS: Ingestion of 7.5 grains of acetanilid four times a day for two days was followed by cyanosis. Sexton. J. C. Acetanilid "Antifebrine." Cincinnati, Lancet Clinic, 1887 (n. s.), 19: 184. Acute miliary tul)erculosis. The ingestion of 15 grains of acetanilid was followed by cyanosis and collapse. SipPEL. H. I'eber Antifebrinboliandlnng. Miinch. med. Wochenschr., 1887, 3-t: 215. (1) Three and three-fourths grains of acetanilid caused severe itching •»f skin. (2) Ingestion of about TOO grains of acetanilid within five days by a phthisical patient was followed by nausea, dizziness, buzzing in the ears, and cyanosis. In one patient 3.75 grains produced partial deafness. 'I'RosT, J. A. Antifebrin. Kansas City Med. Index, 1887, 8: 228. Remittent fever. Acetanilid, 8 grains every six hours, at end of third day caused cyanosis and collapse. Trussewitsch. Discus, of Ansserow : Vergleicluing der, die Wiirmeverluste ausgleiclicndtMi. Wii'kung des Antifebrin in riehernden Organisnien mil der des Antiityrin und Tluillin. Congress russ. Aerzte zu .Moskau. Therap. Mouatsh., Berlin, 1887, 1: 107. Seven and one-half grains of acetanilid caused collapse in a typhoid fever patient 13 years of age. ViNEfsERc;, II. .\. A caution in regard to acetanilide. New York Med. J., 1887, 40: 21 !i. A tji)hoid fever jtatient was given 10 grains of acetanilid every four hours. After doses marked cyanosis. api)eared, with symptoms of collaj)s('. \o.N QuAST, E. A death frrtm antifebrin. (Note by editor of Index.) Kansas ( Ity Med. Index, 1887, 8: 229. The administration of 4 grains of acetanilid every two hours . KIne Antifebriu vc-rgifluug. Tliei'ap. .Monatsh., Berlin, 1889, 3: .381. Tatient took 15 grains of acetauilid, and in an hour 7.5 grains m<»re. 'I'his was followr'd by vomiting, deep cyanosis, twitching of the mu.scles, and double vision. 32 ACETANILID, ANTIPYRIN, AND PHENACETIN. Chakanow. Ein Fall von Vergiftnng mittelst Antifebriu. St. Petersb. med. Wochensclir., 1889, 14 (N. F., 6) : 369. A dose of 15 grains of acetanilid night and morning was followed by cyanosis, nausea, wealvuess, shivering, and irregular heart action. FiJRTH, E. Eine Antifebrinvergiftung. Wien. med. Presse, 1SS9, 30: 652. Sixty-two grains of acetanilid in one dose caused persistent vomiting, cyanosis, shallow and slow breathing, dilation of the pupils, great restless- ness, muscular twitching, delirium, and coma. Gibbons, J. E.. Poisoning by antifebrin. Maryland Med. J., 1889, 21: 183. A drachm of acetanilid taken in one dose caused cyanosis and mild col- lapse. Greene, W. S. Failure of antifebrin as an antipyretic. Univ. Med. Mag., Philadelphia, 1888-9, 1: 228. Ten grains of acetanilid seriously affected the heart iu the case of a well- nourished adult. Haigh, J. Effects of antifebrine upon memory. Med. World, Philadelphia, 1889, 7: 423. Report of two cases in which gradual loss of memory was caused by the long continued administration of acetanilid. Haley, R. A ca.se of antifebrine poisoning. Weekly Med. Rev., 1889, 20: 371. Young woman took 4-grain doses of acetanilid frequently for three days. On the third day she suddenly fell from the chair unconscious. Could not talk at first, and later only with difiiculty. The face was blue, skin cold, and there was much dyspnea. Henschen, S. E. Om s. k. kontrar verkan af febermedel. TJpsala Lakaref. Forh., 1888-9 (4 s.), 24:263. Transl. Abs. Schmidt's Juhrb., Leipzig, 1889, 223: 241. Two cases in which the administration of acetanilid in doses of 11.25 and 3.75 grains, respectively, was followed by a rise of temperature in typhoid fever patients. Mahnert, F. Ueber Intoxicationen mit Antifebrin. Memorabilien Heilbronn, 1889 (N. F.), 9: 321. (1) Girl, tuberculosis: Ingestion of 6 grains acetanilid was followed by profuse perspiration, lividity, and cyanosis. (2) Youth, 16, headache: In- gestion of 15 grains acetanilid in 2 doses with a half-hour interval was fol- lowed by cyanosis, clammy perspiration, accelerated respiration, and rapid heart action. MaeIiichaux. Ein Fall von acuter Antifebrinvergiftung. Deutsche med. Woch- enschr., Leipzig, 1889, 15: 845. Child, 5 months old, was given 3.75 grains of acetanilid. In two and a half hours there was unconsciousness, cyanosis, and collapse. Meyer. Fall von Antifebrin-Intoxication. Allg. Med. Centr.-Ztg., Berlin, 1889, 58: 805. Girl, 13, headache: Ingestion of less than 15 grains of acetanilid was followed by cyanosis and palpitation of the heart. On another occasion 10 grains in 2 doses, with an interval of one hour, caused similar symptoms. LITERATURE ON ACETAXILID POISONING. 33 Pauschingek. Eiu Fall von Antifebrin-Vergiftung. Miinch. med. Wochensclir., 1SS9. 36: 332. Man, 34 : The ingestion of five 15-grain powders of acetauilid at hourly intervals caused vertigo, chilliness, diarrhea, and cyanosis. Penney, E. W. Antifebrin. Times and Register. Philadelphia, 1889, 20 (1) : 1.S3. Two 5-grain doses of acetanilid one hour apart caused collapse in a typhoid-fever patient. Saylob, a. L. Is antifebrin dangerous? Times and Register, Philadelphia, 1889, 20 (1) : 134. A dose of 4 grains of acetanilid to a child 3 years old produced symptoms of collapse. Sembkitzki. Zur Wirkung des Antifebrin. Therap. Monatsh., Berlin, 1889, 3: 267. Woman. 28, typhoid fever : Administration of 4.5 grains of acetanilid caused severe symptoms of collapse. Stein, J. Zur Kenutniss des Antifebrins und seiner Dosirung. Prag. med. Wochenschr.. 1889. 14: 559. Author observed that a dose of 1.5 grains of acetanilid produced halluci- nations in the weak and aged. Wilding. J. Toxic effects of 10 grains of antifebrin. Brit. Med. J., London, 1889, 2: 600. Young man, pulmonary tuberculosis: Ten grains of acetanilid caused collapse. 1890. Armstrong, S. T. A case of acetanilide poisoning. Therap., Gaz., Detroit. 1890 (3). 6: 245. Man. 28: Took 2 drachms of acetanilid in 8 powders at one-half hour intervals for pain. Although he vomited freely, there followed cyanosis, coma, and symptoms of collapse. BoKENHAM. T. .7.. and Jones, E. L. On two cases of poisoning by anilides (Ex- algine and Antifebrin). Brit. Med. J.. London, 1890. 1: 288. Woman, 43, headache : Ingestion of 0.5 drachm of acetanilid in divided doses within two and one-half hours was followed by headache, symptoms of intoxication, cj-anosis, and unconsciousness. Favrat, A. Ueber die Anwendung des Antifebrins in refracto dosi beim Ty- phus Abdominalis und beim Fieber der Phthisiker. (Bern) Leipzig, 189i0. Doses of from 0.75 grain to 1.5 grains of acetanilid given every hour produced chills and cyanosis in 2 cases of typhoid fever. f-ERBis. A. W. Poisoning with acetanilid. Med. Record, New York, 1890, 87: 587. . Woman. 45: Ingestion of 15 grains of acetanilid at 8 and 10..30 a. m. was followed by deep cyanosis, a r)inclied expression, depressed temi)erature, and marked prostration. 82319— Bull. 126—09 3 34 ACETANILID, ANTIPYKIN, AND PHENACETIN. Hartge, A. Eine Antifebrinvergiftung. St. Petersb. med. Wocliensclir., 1890 (N. F.), 7: 69. Student who had been drinking heavily took for insomnia teaspoonful doses of acetanilid from an ounce box until all was taken. Symptoms re- sembled those of anilin poisoning. Recovery was probably due in part to the fact that the stomach contained so much liquid. HattoN, J. B. Some untoward effects from antifebrin. Med. Surg. Reporter, Philadelphia, 1890, 62: 372. (1) Boy, 16, typhoid: Administration of 4 grains of acetanilid was fol- lowed by cyanosis and collapse. (2) Man, 52, sciatica: Two 4-grain doses of acetanilid four hours apart caused cyanosis and collapse. Hermann, E. Beobachtungen liber die Wirkungen und die Anwendungsweise des Antifebrins. Deutsche Med.-Ztg., Berlin, 1890, 11 : 865, 875. (1) Young woman: Two doses of 15 grains of acetanilid with a half hour interval were followed by cyanosis. (2) Following the ingestion of 2 doses of 15 grains of acetanilid the patient felt very weak and was prone to fall asleep whether walking or standing. (3) Ingestion of 1 drachm of acetanilid with suicidal intent was followed by great w^eakness, cyanosis, and persistent vomiting. (4) Girl, 22, acute rheumatism: The ingestion of 7.5 grains of acetanilid 3 times daily until 5 doses had been taken was followed by the appearance of an urticarial eruption. MoLLOFF. Discussion of paper by Khakanoff, 1889. Trans. Med. Surg. Re- porter, Philadelphia, 1890, 62: 83. In two cases collapse followed the ingestion of one 7-grain dose of acetanilid. Morehouse, O. E. Antifebrin rash. Montreal Med. J., 1890-91, 19: 46. (1) Man, 45, pneumonia: Was given 8 grains of acetanilid, and four hours later 8 grains more. An erythematous rash appeared upon the entire body, lasting six days. (2) Girl, 19, typhoid: Six grains of acetanilid caused the appearance of a rash resembling urticaria on face and chest. Four hours later 5 grains more caused the rash to spread to the arms. Temperature fell, accompanied by sweating. Rash disappeared after five days. Preiningeb, v. Otrava antifebrinem. Casopis lekafu v ceskych, 1890, 29 : 225. Abs., Sajous, 1891, 5: A-2. Report of a case of poisoning in which acetanilid appears to have had a cumulative effect. Scott, J. T. Some peculiar results following the use of acetanilide in typhoid fever; report of three cases. Cincinnati Lancet-Clinic, 1890 (n. s.), 24: 65. (1) Child, 3 or 4 years old, typhoid: Six grains of acetanilid 3 times a day caused chills and cyanosis of the entire skin, lasting from one-half hour to one and one-half hours after each dose. Subsequently 3 grains caused a chill, and the administration of the drug was discontinued. (2) Youth, 24, typhoid: Acetanilid, 6 grains 3 times daily, caused on 2 occasions severe chills and profuse sweating. Drug discontinued. (3) Ty- phoid patient was given from 18 to 24 grains of acetanilid daily. Chills appeared and increased in number and se^'e^ity until the patient was having 4 or 5 a day. Acetanilid was discontinued and the rigors ceased. LITERATURE ON ACETANILID POISONING. 35 SuTTLE, I, N. Case of autifebriu habit. New Orleans, Med. and Sure J. 1889-90 (n. s.), 17 (2): 896. The case is reported to illustrate the insidious onset of the acetanilid habit and its pernicious effect on the blood. Man, with necrosis of the tibia, took acetanilid in large doses for pain. He became addicted to its use, and is said to have taken as much as a teaspoouful at a time. The evil effect on the blood was shown by the excessive pallor of the skin. Taylor. W. H. Report of toxic effect of acetanilid. Cincinnati Lancet-Clinic, 1890 (n. s.), 24: 683. (1) Woman, 26, advanced in pregnancy, urine contained albumin: At 5 p. m. and 7 p. m. she took 5-grain doses of acetanilid. At 10 p. m. her physician found her greatly prostrated with deep cyanosis, pinched features, subnormal temperature, cool moist skin, and headache. Her temperature remained subnormal for ten days. (2) Woman, 19, six mouths pregnant: Was given 10 grains of acetanilid for fever. Her temperature fell rapidly to 95°, pulse ran up to 120, and skin became moist and cool. There was slight cyanosis and some prostration. Thomas, W. H. Acetanilid. Report of a fatal case. Indiana Med. J., Indian- apolis, 1890, 9: 67. (1) Author expresses the opinion that 5 grains of acetanilid caused the death of a woman suffering from neuralgia of the head and stomach. May 1, at 4 p. m., the patient's temperature was 104 and her pulse 120, full and strong. She was sponged and given 5 grains of acetanilid. Her tempera- ture fell rapidly, accompanied by symptoms of collapse, and she died nine hours after taking the dose. No record of autopsy. (2) Ingestion of 10 grains of acetanilid was followed by symptoms of collapse. ViEBHUFF. J. I]in Fall von Antifebrinvergiftung. St. Petersb. med. Wochenschr., 1S90 (N. F.), 7: 1.39. Woman took two teaspoonfuls of acetanilid on an empty stomach. She vomited after drinking milk and then a solution of alum, but cyanosis appeared, and she went into a state of collapse which lasted three hours. Wolff, J. Ein Fall von Antifebrinvergiftung. Deutsche Med.-Ztg., Berlin, 1890, 11: .53.5. Woman, 40: Took 7.5 drachms of acetanilid with suicidal intent. This was followed by collapse and coma, and in addition hematuria. 1Q91. P.ROXNER, H. (,'ase of pus in the pericardium treated bv incision and drainage. Brit. Med. J., London, 1891, 1 : 350. Girl, 11: A single dose of 7.5 grains of acetanilid caused a raiiid fall in temperature and symptoms of collapse. " \KK. .1. R. Clinical observations of acetanilide. Med. Surg. Reportci-, I'liila delphia, 1891, 65: 729. Girl, 14: A 4-grain dose of acetanilid caused cyanosis and collapse. DuNAOAN, T. M. Subnormal tcmixTature from aniifchrin. Memphis Med. Month., 1891, 11 : 123. .Man, 10: The ingestion of 11 grains of acetanilid in 2 doses cau.sed cyanosis and subnormal fenijierature. 36 ACETANILID, ANTIPYEIN, AND PHENACETIN. Easley, E. p. Fatffl case of acetauilide poisoning. (Letter to editor.) Amer. Pi-act. and News, Louisville, 1891, 12 : 178. Woman, 22, took by mistake 24 grains of antikamnia, supposed to repre- sent 18 grains of acetanilid. In a few minutes she was wildly delirious. She then became unconscious. Death occurred about ten hours after ingestion of the drug. There was deep cyanosis of the entire body. Autopsy failed to show any lesion as a cause for death. Haee, H. a. Fever: Its pathology and treatment by antipyretics. Phila- delphia and London, 1891, p. 89. A dose of 5 grains of acetanilid caused collapse in a case of typhoid fever. Hawkins-Ambler, G. A. Antifebrin in typhoid fever. Brit. Med. J., London, 1891, 1: 172. (1) Woman, 49, typhoid: Four grains of acetanilid caused collapse. (2) Woman, 35, typhoid: A dose of 4 grains of acetanilid caused marked prostration. HoRTON, F. Prolonged subnormal temperature following the administration of antifebrin. Med. News, Philadelphia, 1891, 59: 712. A typhoid fever patient was given 4 grains of acetanilid and three- fourths of a grain of camphor at 10 a. m., and the same dose at 3 p. m. At 6 p. m. the temperature, which had been 104°, was 97°. It ran between this and 94.6° for forty-eight hours, when it rose rapidly to 104°. Spencer. Poisoning by antifebrin. Canad. Pract., Toronto, 1891, 16: 163. Child, 5, whooping cough : Ingestion of a drachm of acetanilid taken by mistake caused deep cyanosis and slowed respiration. 1892. Grier, W. F. The toxic effects of antifebrin complicated with alcoholism. Med. Rec, New York, 1892, 42: 511. Woman, 45 : Ingestion of 40 grains of acetanilid within eleven hours caused marked cyanosis, increasing rapidity of the pulse, swelling of the tongue, and great restlessness. J. W. C. Case of acetanilide poisoning. Med. Rev., St. Louis, 1892, 25 : 412. Woman, 36, influenza : Took about 40 grains of acetanilid in divided doses within four hours. There followed cyanosis of the face and lips, semi- consciousness, delirium, and symptoms of collapse. Kroneeld, a. Ueber Antifebrinvergiftung. Wien. med. Wochenschr., 1892, 42: 1457. Man, 24 : Took 3 drachms of acetanilid with suicidal intent. Within thirty minutes this was followed by dizziness, nausea, pain in the region of the stomach, unconsciousness, and slight cyanosis. Wakfvinge, F. W. Redogorelse for de forgiftningsfall som forekommit h Sabbatsbergs sjukhus under aren 1879-91. Antifebrin. Hygiea Stock- holm, 1892, 54 (1) : 238. Reports two cases of poisoning by acetanilid. Both patients recovered. LITERATURE ON ACETANILID POISONING. 37 1S93. Bell. G. Vier Falle von Antifebrinvergiftimg. Memorabilieu, Heilbroun. 1S93, 38 (N. F. 13) : 535. (1) Man, past 70: Ingestion of a heaping teaspoonfnl of acetanilid was followed by cyanosis and symptoms of depression. (2 and 3) Each patient took one-half teasijoonful of acetanilid. One complained of dizziness, weak- ness, shortness of breath, and cyanosis of the finger nails, and the other slept for two houi-s. (4) "Woman, 75: Ingestion of an ounce of acetanilid in five days, in teaspoonfnl doses, was followed by weakness, drowsiness, and dyspnea. KoKAWA. B. Antifebrin jutokusei Shiken (antifebrin poisoning). Tokujima Igakkwai Zashi., 1S93, No. 13, p. 8. 1894. Davis. .7. S. A report of three cases of addiction to the coal-tar derivatives. Amer. Med.-Snrg. Bui., 1894, 7: 1490. (1) Man, 63: Chronic bronchitis and cardiac palpitation for two years. Pulse 160 and weak, becoming irregular upon exertion. Anorexia, consti- pation, cyanosis, varying in degree at different times. Had been addicted to the use of acetanilid for a year, taking 40 to 60 grains daily. Last two months he had been running down until he was confined to bed. Dose of acetanilid was reduced to 10 grains daily. He gradually improved and at end of a year was in fairly good health. (2) Man, 32: Suffered from cyanosis, coldness of extremities, insomnia, anorexia, constipation, nervous- ness, and anemia. I'rine: Specific gravity 1.012, albuminous. Heart, rapid and feeble. Had been taking acetanilid for eight months, 12 to 40 grains daily, and his health had failed rapidly. The drug was entirely withdrawn and after a month he was in fairly good condition. After abstaining for eight months he again contracted the habit and his health again became impaired. HiLBEKT, R. Hochgradige Amblyopic nach Gebrauch von Acetanilid. Memora- bilieu, Heilbroun, 1894 (N. P.), 14: 65. Ingestion of three 15-grain doses of acetanilid at short intervals caused vertigo and dimness of visiou. After twenty-ifour hours the sight was again normal. Lynbomndkoff. p. F. Sluchai otravleniya antifebrinom (Antifebrin poisoning). Voyenno-Med. J., St. Petersburg, 1894, 181 (unofficial pt., sec. 2) : 29. Morton, T. S. K. Acetanilid as an antiseptic. Proc. of the Phila. Co. Med. See, 1894, 15: 469. (1) Infant, 14 months: Large wound in hip, packed willi 10 jicr cent acetanilid g.iuze. In four hours the temperature dropped 5°. with symi)- tonis of marked depression. (2) .Man, 57: Extensive sii])erficial scald. Two drachms of acetanilid dusted over the surface caused cyanosis, ex- ceHslve yawning, delirium, and synii>tonis of depression. \\'(>tn>s, (i. W. The use of ncelaiiilid in medicine and surgery. J. Amer. .Med. A8SOC., Chicago, 1894, 23: KKJ. The a[>[)!icali: 1767. Man, 22 : Habitual use of bromo-seltzer over a period of six months caused mental dullness and depression, general weakness and indisposition to exertion, and cyanosis. The expression was vacant, the breath fetid, pulse rapid on exertion. Cassady, D. Acetauilid poisoning by headache tablets. J. Amer. Med. Assoc, Chicago, 1906, 47: 2012. Woman, 45 : Accustomed to taking " Steam's Headache Cure." One wafer an hour for three hours caused cyanosis and symjitoms of collapse. (lOEPP, R. .M. A case of acetauilid poisoning from absorption. J. Amer. Med. Assoc, Chicago. 1906, 47: 359. Woman, 37: (1) For eleven months she had dressed an ulcer of the leg with acetauilid, aiul during this time she had run down in health and lost 70 pounds. Suffered from cyan-IM.~>. DK Gassicourt, C. Discussion of i)aper l)y Doscroizilles. L'emploi de I'anti- pyrine chez les enfants. .1. mC'd., Paris, 1885, 8: 91 L Two eases In which the ingestion of antipyrin was followed by the ap- pearance of an eruption of bright red spots. Dkai'kk, \V. II. Aniipyrin and its effects. .Med. liec, New York., 188.5, 27: 414. An erujition n'scnibling that of measles occurred in G out of 20 cases of typhoid tr('ale dans l;i (ir-vrc fypliuVdc. I'aris, 188.5. A roseola followed tli<- iHoiongcMl use of antipyrin in lyplioid fever. 82.310— Bull. i2*>—(y.) i 50 ACETANILID, ANTIPYEIN, AND PHENACETIN. GiORGiEKi, C. Suir eruzione cutanea per 1' uso dell' antlpirina. Gazz. med. ital. lomb., Milano, 1885 (8. s.), 7: 273. Two cases in which an eruption followed the ingestion of antipyrin. GuTTMANN, P. Ueber antipyretische Mittel. Berl. kiln. Wochenschr., 1885, 22 : 401. In 6 cases out of 297 an exanthematous eruption followed the ingestion of antipyrin. Kaatzer. p. Antipyrin bei Phthisis. Deutsche med. Wochenschr., Berlin, 1885, 11: 270. In 2 cases the ingestion of antipyrin was followed by the appearance of an exanthematous eruption. PtJSiNELLi. Ueber Antipyrin. Deutsche med. Wochenschr., Berlin, 1885, 11: 145. In 7 cases of typhoid the ingestion of antipyrin was followed by the ap- pearance of an exanthematous eruption. RoLLET, M. F. Note sur Tantipyrine chez les tuberculeux. Lyon med., 1885, 49: 453. An eruption appeared in 1 out of 5 cases of tuberculosis treated with antipyrin. Roux-Seignoret. Sur un cas de fievre typlioi'de, traite par Tantipyrine. Erup- tion rubeoliforme au dixieme jour. France med., Paris, 1885, 2 : 921. Typhoid : The ingestion of antipyrin was followed on the tenth day by the appearance of a morbilliform eruption, covering the entire body. Sartorius, E. Antipyrin in der Kinderpraxis. Erlaugen, 1885. Child, 6 : Ingestion of antipyrin was followed by the appearance of an exanthematous eruption. Secretan, L. Antipyrine et rhumatisme. Rev. med. Suisse Rom., Geneve, 1885, 5: 718. The ingestion of antipyrin was followed by the appearance of a morbilli- form eruption, covering the entire body. Shattuck. G. B. The results of the use of antipyrine at the Boston City Hospital. Boston Med. and Surg. J., 1885, 113: 78. In a small proportion of cases the exhibition of antipyrin was followed by the appearance of an eruption. Welt, S. Klinische Beobachtungen fiber die antifebrile Wirkung des Anti- pyrins und Thallin nebst Bemerkungen iiber individuelle Antipyrese. Deutsches Arch. klin. Med., Leipzig, 1885-6, 38: 81. Thirteen out of 122 patients treated with antipyrin developed an ery- thema. Ziteke, J. X. Antipyrine. Therap. Gaz., Detroit, 1885 (3. s.), 1: 517. Author observed cases in which exanthematous eruptions followed the prolonged use of antipyrin. 18S6. Blomfield, J. E. Two cases of antipyrin-rash. Practitioner, London, 1SS6, 36: 261. Two cases of acute phthisis in which the ingestion of from 7 to 12 grains of antipyrin 3 times daily was followed by the appearance of an eruption upon the skin. LITERATURE OX AXTIPYRIN POISONING. 51 Cattani. G. Deir esautema antipiriuico. Gior. ital. d. mal. ven., Milauo, Six cases in which an eruption followed the ingestion of antipyriu. DE Renzi. E. Eruzione cutanea prodotta dall' antipirino. Kiv. clin. e teran Xapoli, 1886, 8: 57. • Male, typhoid: Ingestion of 4.5 drachms of autipyrin within three days was followed by an erythematous eruption. Fraenkel. a. Ueber Antipyrinbehandlung des acuten Gelenkrheumatismus. Deutsche med. Wocheuschr., 188(5, 12: 772. Man, 39, articular rheumatism : The ingestion of 1.25 drachms of anti- pyriu daily for six days was followed by the appearance of an erythema covering the entire body. Fraxkenbehg, J. H. Antipyriue. Med. Rec, New York, 1886, 29: 585. Seven cases in which the ingestion of antipyriu was followed by an eruption on the skin. In one the quantity taken was 5 drachms within two weeks in 15-grain doses. In the other the quantity was 1 to 3 ounces in the same period of time. Fruitnight, J. H. Kairine and antipyrine. Med. Rec, New York, 1886, 29: 647. Acute phthisis : Five grains of autipyrin given every four hours pro- duced a bright red miliary eruption. GoLBiEwsKi. E. Feber die Wirkung von Antipvrin bei Gelenkrheumatismus. Berl. kliu. \Vochenschr., 1886, 23: 463. In about 70 cases there wore only 2 instances in which an exanthem re- sembling urticaria followed the use of antipyrin. Laache, S. Ein Fall von •' kontrJirer " Antipyrinwirkung. Centrbl. klin. Med., Leipzig, 1886, 7: .545. Man. phthisis: The ingestion of 0.5 drachm dose of autipyrin was fol- lowed by a chill and rise of temperature. On the next day a scarlatiniform eruption appeared upon the skin. Laube. l^ltude clinique sur la valeur de I'antipyriue specialement appliquee a, la therapeutique infantile. Rev. mens. mal. I'enf., Paris, 1886, 4: 57. On four occasions a morbilliform eruption was observed in children fol- lowing the ingestion of antipyrin. -Masius et Snyers, p. Contribution a I'etude do riintipyrin(>. Hul. Acad. roy. xnM. Relg., Bruxelle.s, 1886 (3. s.), 20: 547. Case in which an exanthematous eruption followed thi' ingestion of anti- pyrin. Dau.v. E. (). Rash produced by antipyrin. I'.rit. .Med. .1., London, 1887, 1: 111. Two cases in which a morbilliform eruption followed the ingestion of antiityrin. IIaykm. MfMles diKlniinistratioii df riiiitipyrine. J. nu'd. I'ai-is, 1S87, 12: 708. Ingestion of 0.5 «lra(lnii of anli|iyrin gave rise to an inlcnse crylliema. IIayh, .7. M. SIrtugbing following a liypodennie injefljoii of iintiiiyiin. .Med. Iter;., New York, 1887, «2: 486, Inje^'tion of 12 grains of antipyrin dissolved in water was followed by a severe urticarial eruption, and a slough the size of u silver quarter. 52 ACETANILID, ANTIPYEIN, AND PHENACETHST. JozEFOWicz. On the antipyrin rash. Proceedings of the Kovno Medical So- ciety, 1886, No. 2, p. 17 (Abs. Lond. Med. Record, 1887, 15: 264). Two cases of exanthem following the ingestion of antipyrin, one with and the other without severe itching. Leitzmann, G. Eine Nebenwirkung des Antipyrin. Berl. klin. Wochenschr., 1887, 24: 531. Woman, pneumonia : A dose of 15 grains of antipyrin was followed in four hours by a chill and vomiting, and later by an erythema. Martini, V. Orticaria per antipirina. Boll. d. sez. d. cult. d. sc. med. n. r. accad. d. flsiocrit. di Siena, 1887, 5: 114. Urticaria and intense itching followed the ingestion of antipyrin. Paget, W. S. Rash produced by antipyrin. Brit. Med. J., London, 18S7, 1 : 210. The ingestion of antipyrin for eight days on an average of 1 drachm daily was followed by the appearance of a bright red rash. SCHWARZ. Ein Fall von Antipyrinexanthem. Miinch. med. Wochenschr., 1887, 34: 59. Woman, 27, typhoid : Ingestion of 9 drachms of antipyrin in fourteen days was followed by a severe chill and then by a m'orbilliform rash with severe itching. StE, G. De I'antipyrine contre la douleur. Compt. rend. acad. sci., Paris, 1887, 104: 1085. Author had observed an eruption resembling that of scarlatina or urti- caria following the ingestion of antipyrin in doses of from 1 to 1.5 drachms daily. Spitz, B, Ein eigenthiimlicher Fall von Dermatitis hervorgerufen durch Anti- pyrinbehandlung. Therap. Monatsh., Berlin, 1887, 1 : 347. Girl, 20, typhoid : One-half drachm doses of antipyrin were followed by a morbilliform rash with subsequent desquamation. Victor, P. Antipyrin rash. Indian Med. Gaz., Calcutta, 1887, 22: 241. Boy, 14, typhoid : Between June 26 and July 6 received 300 grains of anti- pyrin. A vesicular and papular rash appeared over the whole body, and lasted six days. Whitehouse, J. S. A case of antipyrin poisoning. Med. Rec, New York, 1887, 32: 706. The ingestion of 7.5 grains of antipyrin was followed in two minutes by severe gastric pain and soon after by the appearance of an urticarial erup- tion and symptoms of collapse. ISSS. Barber, C. F. Some toxic effects of autipyrine. Med. Rec, New York, 1888, 33: 14. Ingestion of 15 grains of antipyrin was followed by the appearance of an urticarial eruption with intense itching. The face was much swollen, * features being obliterated. LITERATURE ON ANTIPYRIN POISONING. 53 BoKENHAM, T. J. Some therapeutic uses of antipyrin. Practitioner, London, 1888, 40: 266. (1) Ingestion of 20 grains of antipyrin 3 times a day for fourteen days by a child was followed bj- malaise and the appearance of an eruption resembling that of both urticaria and scarlatina. (2) Ingestion of an- tipyrin was followed by drowsiness, vertigo, delirium, and diarrhea. (3) The first dose of antipyrin was followed by symptoms of depression. (4) Antipyrin caused the appearance of a rash like that described in case 1. Cehak. Zur Wirkung des Antipyrins. AUg. Wien. med. Ztg., 1888, 33: 316. Ingestion of 15 grains of antipyrin was followed by severe sneezing, dyspnea, and swelling of the entire face and inside of the mouth. In 2 cases erythema followed the ingestion of antipyi'in. Clabemont, C. C. Antipyrin rashes. Brit. Med. J., London, 1888, 2 : 943. In 2 cases an eruption followed the ingestion of antipyrin in tj^phoid fever. DuRAND, .J. Eruption scarlatiniforme causee par I'antipyrine. Gaz. hop. Toulouse, 1888, 2: 225. Man, 55, neuralgia : A scarlatiniform eruption followed the ingestion of 0.5 drachm of antipyrin. DuTT, U. K. Idiosyncrasy with regard to antipyrin. Brit. Med. J., London, 1888, 1: 1147. Ingestion of antipyrin was followed by violent itching, tingling, and burning of the throat and skin, and sneezing. No eruption. Gbognot. Sur un cas d'oedeme oonseoutif a I'absorption de I'antipyrine. Bui. gen. therap. [etc.], Paris, 1888, 115: 134. Man, 35, facial neuralgia : Fifteen minutes after taking 15 grains of analgesin, edema of the face developed. Habdy. Sur I'emploi therapeutique de I'antipyrine et de I'acStanilide. Bui. Acad, med., Paris, 1888 (2. s.), 19: 245. Man, 30 : Developed a scarlatiniform eruption after taking antipyrin. Jennings, O. On poisoning by antipyrin. Lancet, London, 1888, 1: 3(54. (1) Ingestion of 2.5 grams of antipyrin daily for eight days was fol- lowed by the appearance of an eruption over the whole body, swelling of the face, symptoms of collapse and prostration. (2) Young woman took 5 grams of antipyrin a day for rheumatism. On the second day she was found .swaying back and forth, and repeatedly crying that she had lost her memory and was going mad. She subsequently had an attack of gastro- enteritis, (3) Woman. The ingestion of aiitii)yrln was followed by a swelling of the body, dysimea, and the appearance of an erniilion. Lanpheak, E. a pet-uliar effect of aiitii)yriM. KansMs City Med. Index, 1888, 9: 155. Woman, 52: Ingestion of 1.5 ounces of antiiiyrln in one week was on 2 occasions followed by deep cyanosis and swelling <>f th<> f>ici> and extremities. 54 ACETANILID, ANTIPYEIN, AND PHENACETIN. Macdonald, a. Antipyrin and idiosyncrasy. Brit. Med. J., London, 1888, 1: 296. Girl, typhoid : Ingestion of 3 doses of antipyrin daily for twelve days was followed by the appearance of an urticarial eruption over the entire body except the face. Mahnert, F. Studien und Erfahrungen iiber Antipyrin. Mittheil. Ver. Aerzte in Steiermark, 1888, 24: 62. Author states that he had seen but 1 case in which a morbilliform rash followed the ingestion of antipyrin. Mayet. Bui. mem. soc. de therap., Paris, 1888 (2. s.), 15: 33. Ingestion of 45 grains of antipyrin was followed by an intense urticarial eruption ; 7.5 grains taken later caused swelling of the eyelids and entire face. Mazzotti, L. Esantema antipirinico per iniezioni sottocutanee d "antipirina ed eruzione di herpes zoster sopra di esso. Gior. ital. mal. ven., Milano, 1888, 23: 210. An eruption followed the subcutaneous injection of antipyrin. Oliver, T. Clinical experience of some of the more I'ecently introduced drugs. Lancet, London, 1888, 1: 868. A herpetic eruption followed the ingestion of antipyrin taken for neu- ralgia. Ollivier, a. Bui. Acad, med., Paris, 1888 (2. s.), 19: 229. Child, chorea : Ingestion of antipyrin was followed by the appearance of an erythematous rash. Ory. Contre-indications de I'antipyrine, son emploi dans la polyurie. J. m^d. Paris, 1888, 14: 486. Forty-five grains of antipyrin taken during the day gave rise to a miliary eruption over the entire body. Stack, J. J. Antipyrin. Lancet, London, 1888, 2: 1112. On 3 occasions the ingestion of a 10-grain dose of antipyrin caused the appearance of an urticarial eruption over the entire body with itching and a disagreeable sense of uneasiness. TisNE. Eruption due a I'usage de I'antipyrine. J. med. Paris, 1888, 15: 327. The ingestion of antipyrin was followed by the appearance of a scarlatini- form eruption. Wilson, J. C. Note on antipyrin as an analgesic. J. Nerv. Ment. Dis., New York, 1888 (n. s.), 13: 42. In two or three instances a transient scarlatiniform eruption followed the use of antipyrin. WiNDELSCHMiDT. Ueber die Wirkung des Antipyrin bei der Menstruationscolik, Allg. med. Centr.-Ztg., Berlin, 1888, 57: 1029. Boy, 7 : A dose of 4.5 grains of antipyrin was followed by the appearance of an urticarial eruption and high fever. LITERATURE ON ANTIPYRIN POISONING. 55 1S89. Amon. H. Subkntane Antipyrin-Injektion bei akxitein (ielenksrheumatismus. Interuat. kliu. Kimdscliuvi, Wien, ISS9, 3: 123. A small superficial patch of gangrene of the skiu followed the subcutane- ous injection of antipyrin. Boucher. Eruption due a I'antipvrine. Bull. soc. med. Rouen, (1889) 1890 (2. s.), 3: 29. A morbilliform eruption followed the ingestion of antipyrin. Gkandclement. Indications et dangers de I'antipyrine. Lyon med., 1889, 60: 414. Man, G5 : One or 2 doses of antipyrin of 7.5 grains each were followed by the appearance of an eruption upon the skin. It reappeared every time the patient took antipyrin. Ferret. S.. and Devic, E. Des eruptions rubeoliformes dues h I'antipyrine. Province med., Lyon, 1889, 3: 301. Girl, 5: A morbilliform eruption follow^ed the ingestion of antipyrin. Watkins. W. Antipyrin ; results following its administration. Lancet, London, 1889, 2: 903. Woman. 37, headache : A dose of 10 grains of antipyrin was followed by great swelling of the upper lip. 1890. Dubousquet-Laborderie. Traitement de la coqueluehe par I'antipyrine. Se- maine med., Paris, 1890, 10: 154. Ill effects were noted in 15 out of 300 cases treated with antipyrin, prin- cipally a scarlatiniform eruption or gastric disturbance. Lewis. D. C. Five hours with 15 grains of antipyrine. Med. Brief, St. Louis, 1890, 18: 282. Half an hour -after taking 15 grains of antipyrin the patient's face be- came swollen, the sight blurred, the hearing indistinct, and an urticarial eruption made its appearance. 1891. de MOLfeNES, P. Ervthr-mc antipyrhiiquo. Ann. derniat. syph., Paris, 1891 (3. s.), 2: 384. An erythematous cruiitioii lasting aliout six days followed the ingestion of antipyrin. Gliazstein, I. K. Kazuist t. n. lekarst. sypei. (So-called drug exanthem). Meditsina, St. Petersburg, 1S91, 3: 405. Cited by Fournier, 1892, p. 490. (1) An erythematous eruption fcjllowed the ingestion of 7.5 grains of antipyrin. SubscnpuMitly another dose of the drug was followed l)y similar symptoms. (2) On 2 occasions an eruption ai)iieared after the ingestion of 3 doses of aii1ii»yrin. 2.5 grains eafli, in the case p»'arance of an erui)tion upon the skin. \VKCii8Er.MAN.N, W. I'eber .VnlipyriiicxiiMdiem. IxmiIscIk" med. Woohenschr., lA'ipzig and Berlin, 1898, 24: .335. Five caseH In which llif anlipyn'M w;is followi-d iiy mani- festations on the part of the skin. 62 ACETANILID, ANTIPYRIN, AND PHENACETIN. 1899. D'AuLNAY, G. R. Intoxication par la migraiuine. Bui. gen. de therap. [etc.] Paris, 1899, 137: 857. The ingestion of 7.5 grains of migrainine was followed by pain in the stomach, urticaria, diarrhea with tenesmus, burning on micturition, rapid pulse, and accelerated respiration. X901. Troisfontaines, p. Eruption pemphigoTde antipyrinique. Belgique mM., Gand. Haarlem, 1901, 8 (2) : 1. Man, 38, headache: Two 1.5-grain doses of antipyrin with a two-hour interval were followed by vomiting and diarrhea, and the appearance of an itching scarlatiniform eruption. 190S. Bernard, J. i*ccidents consecutifs a I'absorption d'antipyrine. Gaz. med. Pi- cardie, Amiens, 1902, 20: 407. A nervous patient, 35 years of age, took 10 grains of antipyrin and 3.75 grains of hydrobromate of quinine. Purpuric spots appeared upon the palm, sole, and fingers, followed by desquamation. There was also redness of the urethra and glans, with discharge. Cardoso, A. Um casa de idiosyncrasia para a antipyrina. Med. mod., Porto, 1902, 9: 250. Crouzel, E. Sur un case d'idiosyncrasie. J. med. Bordeaux, 1902, 32: 794. Every time that the author took antipyrin, 3.75 grains, there appeared on the dorsum of the left hand a red erythematous patch, painful on pressure. 1903. Claverie. Eruption, erythemato-bulleuse due a I'antipyrine. Rev. m§d. I'Afrique du nord, Alger, 1903, 6 : 2228. Man. 72, headache : Six hours after the ingestion of 15 grains of anti- pyrin erythematous spots appeared all over the body, with the subsequent development of vesicles and bullae. Danlos. Eruption a type d'erytheme polymorphe produite par I'antipyrine. Bui. soc. frang. dermat. syph., Paris, 1903, 14: 233. On two occasions the ingestion of antipyrin was followed by nervousness, insomnia, a skin eruption, and the development of blisters in the mouth and upon the genitals. Dariek. Antipyrinides. Rev. internat. med. chir., Paris, 1903, 14: 362. A bullous eruption upon the dorsum of the hands, and vesicles upou the auricle and knee followed the use of antipyrin. Nagatomi, J. (Antipyrin exanthemata.) Chingai Iji Shinpo, Tokio, 1903, p. 515. Roux. Un cas d'intoxication par I'antipyrine. Poitou med., Poitiers, 1903, 18: 18. Woman, 54, headache : Two 7.5-grain powders of antipyrin were followed by dyspnea, and great redness and swelling of the skin of the face and body. Shishido, S. (Antipyrin exanthemata.) Chingai Iji Shinpo, Tokio, 1903. p. 217. LITERATURE ON AXTIPYRIN POISONING. 63 1904. Behaegei.. Erytheme pigmente fixe dfl a I'antipj-riue. J. med. Bruxelles, 1904, 9: 420. An eruption of reddish-brown spots followed each dose of 22.5 grains of antipyrin. Di'bois-Havenith. Erytheme pigmente flxe dfl a I'administration de I'anti- pyrine. Presse med. beige, Bruxelles, 1904, 56: 731. An erythematous eruption followed the ingestion of 22.5 grains of auti- pyrin. LowY. K. I'eber zwei Falle von Autipvrin-Exanthem. Arch. Dermat. Syph., Wien, 1904, 68: 167. (1) The ingestion of a teaspoonful of headache powder was followed by general pruritus, an eruption upon the skin, and marked depression. (2) A dose of 15 grains of antipyrin was followed by a morbilliform eruption and great swelling of the face. Malherbe, H. Verge noire par eruption antipyrinique. J. mal. cutan. syph., Paris. 1904, 16: 499. The ingestion of 22.5 grains of antipyrin was followed by an almost black discoloration of the genital organs, which was slow in disappearing. 1905. Bruning. Zur Pathogenese der Antipyrinexantheme. Charite-Ann., Berlin, 190.5, 29: 787. Each time the patient took antipyrin he suffered from ulceration of the mucous membrane of the mouth and a vesicular eruption upon the body, including the genital organs. Yamada, K. Noch einmal fiber die Antipyrinexanthema. (Ausz., fac. 4.) Hifubyog. Kiu Hiniokibyog. Zasshi, Tokyo, 1905, 5: 423. 1906. Degle, II. Eiiie eigentiimliche Form einer toxischen Dermatose nach Antipy- ringebrauch. Wien. med. Presse, 1906, 47: 21.54. The ingestion of 15 grains of antipyrhi twice daily was followed by the appearance of an eruption resembling miliaria riii)ra. 1007. (iiLLES. Intoxication par rantipyrine choz une accouchee. Toulouse med., 1!M»7 (2 .s.), 9: 26. A doso of 7.5 grains of antipyrin was followc'd by tlie ajtpearance of an erytliematous eruption. f)n the next day there was edema of the lower extremities and profuse dijirrhcM. (A.SKS OK fOLLAPSK. In tlif! following: instances collapse formod the mo.st prominent . feature of the clinical history. The symptoms e.xhihiled were in most cases the usual ones of pallor of the skin, coldness of (he ex- treniilies. <■()](] ptrspiration. rapid and f('el)le pulse, and an anxious and jiinchcd (!\{jre>sion, the severity of the symptoms depending on 64 ACETAlSriLID, ANTIPYRIN, AND PHENACETIN. the intensity of the poisoning. In many of the cases the skin, diges- tive tract, or other parts of the body presented abnormal symptoms in addition to those of collapse. Cyanosis, however, appeared in only a very few instances. 1884. HucHAED. Nouveaux faits relatifs a Taction pbysiologique et therapeutique de I'antipyrine. Bui. mem. soc. therap., Paris, 1884 (2 s.), 11:205. Child, 7, typhoid: Collapse followed the ingestion of 12 grains of anti- pyrin. The case resembled one of carbolic-acid poisoning. Israel, E. Om Antipyrinet. Hosp.-Tid., Kjobenhavn, 1884 (3 s.), 2: 1129. Boy, 13, typhoid : Collapse followed the ingestion of antipyrin. May, F. Antipyrin, das neueste Antipyreticnm. Deutsche med. Wochenschr, 1884, 10: 390. Man, 25, pneumonia : One-half drachm of antipyrin at 7 and 8 p. m., and 15 grains at 9 p. m. were followed by severe collapse. 1885. Blore. Death after the use of antipyrin; necropsy. Lancet, London, 1885, 1: 882. Woman, 35: At 3 p. m., her temperature being 103° and pulse 132 and feeble, she was given 35 grains of antipyrin, and three hours later one- half of this quantity. By 11 p. m. her temperature was normal. She passed a restless night, with diarrhea and vomiting, fell into a condition of collapse, and died thirty-two hours after taking the antipyrin. BoLDT, see Draper, W. H. Med. Bee, New York, 1885, 27 : 414. In 2 cases of puerperal septicemia the ingestion of 1 drachm of anti- pyrin was followed by prostration and semicoma. The symptoms resem- bled those of carbolic-acid poisoning. CossMANN. Collaps nach Antipyrin. Prakt. Arzt, Wetzlar, 1885, 26: 106. Girl, 19, typhoid : Collapse followed the ingestion of 1 drachm of anti- pyrin in 2 doses, with a two-hour interval. Favre, C. De I'antipyrine dans la fievre hectique des tuberculeux. Lyon, 1885. Pulmonary tuberculosis. A dose of 22.5 grains of antipyrin was followed by nausea, chills, and coldness of the lower extremities. Later, a drachm administered within five hours produced a tendency to collapse. GoTZE. Einige Bemerkungen fiber die Wirkung des Antipyrin. Berl. klin. Wochenschr., 1885, 22: 145. (1) Five hours after taking 1.25 drachms of antipyrin in 3 doses the temperature fell to 96.6°, with cyanosis and symptoms of collapse. A similar result followed the ingestion of 1 drachm, and later 0.75 of a drachm. (2) Boy, 14: The ingestion of 37.5 grains of antipyrin in 3 doses was followed by symptoms of collapse and a fall in the temperature of 9°. HuMBERT-MoLLiERE. Discussion of paper by RoUet. Lyon med. 1885, 49: 472. Collapse followed the ingestion of antipyrin in the case of an old tuber- culous woman. LITERATURE ON ANTIPYRIIv POISONING. 65 Jaccoud. Sur les efl'ets antitberuiiqiies de l;i tlialliue. P>ul. acad. ined., Paris, 1SS5 (2. s.), 14: 1443. Phthisis: (1) lugestiou of 0.5 drachm of aiitipyrin daily caused, on the third day. a fall of 9° in the i>atieut's teniiterature within three hours. (2) Serious collai»se followed the ingestion of 7.5 grains. Mason, A. L. Typhoid fever at the Boston city hospital in 18S4-18S5; with remarks on the use of antipvrine. Boston Med. and Surg. J., 18S5, 113: 535. Out of KKt typhoid-fever patients treated with antipyrin, 6 showed symptoms of collapse within an hour after the ingestion of 20 or 30 grains of the drug. ScHtJLLER. <;. Collaps nach Antipyrin. Prakt. Arzt, Wetzlar, 1885, 26: 145. Youth, 21. typhoid: Severe collapse followed the use of antipyrin. ScHULZ, li. Rehandlung des Typhus abdominalis mit Antipyrin. Deutsche med. Wochen.schr., Berlin, 1885, 11 : 333. The ingestion of 1 drachm of antipyrin in 2 doses was followed by symp- toms of collapse. Stbauss. Zur Wirkuug des Antipyrius. Berl. klin. Wochenschr., 1885, 22: 5G2. Typhoid : The ingestion of 1.25 drachms of antipyrin in 3 doses was fol- lowed by collapse. 1886. SucHARi). Soc. vaudoise de med., Oct. 10, 1885, Rev. med. de la Suisse rom., Geneve, 1886, 6:56. Phthisis: Collapse, followed by death, resulted from the ingestion of about 12 grains of antipyrin during the night. BuNGEBOTii. Beobachtungen iiber das Antipyrin bei infecticisen Erkrankun- geu der Kinder. Charite-Ann., Berlin, 1886, 11:599. (1) In 22 cases of typhoid fever in children mild collapse followed the administration of antii)yrin in 3 cases; severe collapse in 3 cases; dan- gerous cardiac weakness in 2 cases; and a rubeola-like eruption in 1 case. I>EMi£:viLLK. Soc. vaudoise de med., Oct. 10, 1885. Kev. med. de la Suisse rom., Geneve, 1886, (>: 56. Serious collapse, with coma lasting three days, followed the ingestion of 45 grains ctf antipyrin in 2 doses within two hours. Gkaham, VV'. Unpleasant effects of antipyrin. Canada Lancet, Toronto, 1885- 1886, 18: 138. Twelve grains of antipyrin taken every three luairs produced severe col- lapse and an eruption of purpuric macuhe upon tlic back. PosAiJSKY, S. Antifiyrin bei crupiiser Pneumonic I »ciitsclie nicd. Woclieiiscbr., Berlin, 1886, 12": 636. Lobar pneumonia : In 5 cases out of 25 collapse followed the ingestion <»f a few doses of antipyrin. In 2 cases there was also an erythema. Rkiiii.kn, M. Ueber Antipyrin. Deutsches Arcli. kiln. .Med., Leipzig, l,s,s5-(5, :JS: 5;i4. Two cases of collapse in 89 cases treated witli antii»yriii; 1 in tubercular meningitis, the other in gangrene of the luug. 82:il9— P.ull. \2(i—ir.t 5 66 ACETANILID, AFTIPYEIN, AND PHENACETIN, Welch, W. M. Clinical note on the use of antipyrin, Med. News, Philadelphia, 1886, 48 : 10. A single dose of 10 grains of antipyrin administered in typhoid fever produced symptoms of collapse. 1887. Bebnotjlli, D. Zur Kenntniss der Nebenwirkungen des Antipyrin. Cor.-Bl. f. schweiz. Aerzte, Basel, 1887, 17: 357. Woman, 52, rheumatism : A dose of 15 grains of antipyrin was followed by mild collapse and vomiting. A month later a similar dose produced vomiting, cyanosis of lips, dyspnea, and a scarlatiniform eruption. Bbooks, L. J. Clinical value of antipyretics. Med. Times, Philadelphia, 1886-87, 17: 794. (1) Boy, 9: The ingestion of 10 grains of antipyrin was followed by cyanosis and symptoms of collapse. (2) Symptoms of collapse followed the ingestion of two 10-grain doses of the drug. (3) A morbilliform eruption appeared after the use of antipyrin. Cheron, p. Contribution a I'etude du danger de I'antipyrine. Union med., Paris, 1887 (3. s.), 43: 907. Typhoid : Collapse followed the ingestion of 15 grains of antipyrin in two doses with an interval of five hours. Hays, G. D. A caution as to the use of antipyrin. New York Med. J., 1887, 45: 100. Three cases of collapse following the ingestion of antipyrin. One was a case of acute rheumatism, and the other two of typhoid fever. Henderson, R. B. Two cases of poisoning from antipyrine and nux vomica. Med. Rec, New York, 1887, 31 : 95. Report of two cases of poisoning, in which both antipyrin and nux vomica were administered. Both were characterized by prostration, and in one death resulted. Note on collapse following antipyrin. Indian Med. J., Lahore, 1887 (n. s.), 1 : 273. The ingestion of 10 grains of antipyrin by a soldier to reduce temperature was followed by cyanosis and collapse. Jacoby, G. W. Med. Rec, New York, 1887, 32 : 581. Author had seen collapse follow a dose of 20 grains of antipyrin. LuTAUD. Contribution a I'etude des dangers de I'antipyrine. J. med., Paris, 1887, 12: 825. The ingestion of 15 grains of antipyrin in two doses, with a three-hour interval, was followed by collapse. Mendel. Die Anwendung des Antipyrin bel Nervenkrankheiten. Therap. Monatsh., Berlin, 1887, 1: 259. Author had observed collapse following the ingestion of antipyrin in two cases. Weill, E., and Chabannes. Observation de fievre typhoi'de traitee par I'anti- pyrine et terminee par la mort. Lyon med., 1887, 56: 426. Typhoid: The ingestion of 9.5 drachms of antipyrin was followed by a relapse, during which the patient received 6.25 drachms in seven days. This was followed by collapse and death. LITERATURE ON ANTIPYRIN POISONING. 67 Wilson. J. C. Note on antipyrin in the treatment of sciatica. Med. Times, Philadelphia, 1SS7-SS, 18: 4S. . Alarming prostration followed the administration of 5 grains of anti- pyrin to a very fat woman with weak heart walls. 188S. BiNET. P. Soc. med. de Geneve. 5 Sept., ISSS. Rev. med. de la Suisse rom., Geneve, 1SS8, 8: 635. Author cites a case in which a dose of 7.5 grains of antipyrin was fol- lowed hy swelling of the eyelids, an itching eruption, nausea, vertigo, pre- cordial pain, and loss of consciousness. D'EsPiNE, cited by Cordet in discussion of paper on " Des accidents produits par I'antipyriue." Rev. gen. cliu. therap., Paris, ISSS, 2: 709. Author states that he had seen collapse in children with pneumonia follow the ingestion of even small doses of antipyrin. Drasche. Ueber die Nebenwirkungen des Antipyrins. Wien. klin. Wochen- schr., ISSS, 1 : 571. Typhoid: An enema containing 0.5 drachm of antipyrin was followed by a copious hemorrhagic exanthem and collapse, which ended fatally. Hafftek, E. Cor.-Bl. f. schweiz. Aertze, Basel, 18SS, 18: 743. Man, Go, pneumonia : Fatal collapse occurred one hour after the inges- tion of 15 grains of antipyrin. MoLLiERE, H., cited by Peter in " Les traitements de typhoTdiques." Bui. med., Paris, ISSS, 2: 551. (1) Typhoid patient. 52 years of age, after taking antipyrin for fifteen days, died of cachectic purpurea and debility induced by the drug. (2) In- gestion of antipyrin by a typhoid-fever patient 2() years old caused uremic convulsions, which ended fatally. LoEBL, .J. M. Erfahrungen iiber Antipyrin. Wien. med. Presse, 1S8S, 29: 121. Child, 6, typhoid : Ingestion of four doses of antipyrin, 3.25 grains each, was followed by cyanosis and symptoms of collapse. MtJLLER, II. Ueber toxische Nebenwirkungen des Antipyrin. Cnr.-BI. f. Schweiz. Aerzte, Basel, 188S, 18: OSl. Girl, 10, acute articuhxr rheumatism : Each dose of 11 grains of anti- pyrin was followed by nausea, dizziness, itching, and a tendency to col- lapse. Payne. Discussion of paper by R. H. Lewis. North Carolina Med. J., Wil- mington, ISSS, 21: 297. Ingestion of 8 grains of antipyrin was followed by collapse. Rapin, E. Accidents dus tl rantii)yrine. Rev. med. de la Suisse rom., Gen&ve, 1888, 8: 687. Woman, 28, sciatica : Tlie ingestion of 1-grain doses of antli»yriii for six days was followed by cyanosis, symptoms of collapse, and the appearance of an Itching eruption. Rousseau. Des accidents causes par I'antipyrine. Rev. g^n. clin. llicrap., Paris, 1888, 2: 515. The ingestion of 7.5 grains of aiidpyrin was fnllowed by itching of tlie facr*, swelling of the eyelids, and synijitonis of collapse.'. 68 ACETANILID, AlS'TIPYKIX, AND PHENACETIN. Sykes. Discussion of paper by E. H. Lewis. North Carolina Med. J., Wil- mington, 1S8S. 21: 2.97. (1) Two doses of 10 grains each of antipyrin caused collapse and death in a girl of 10. (2) Typhoid : Ten grains of antipyrin caused coma and collapse. 1©89. Crombie, a. The comparative value of antipyrin. antifebriu, and phenacetin as antipyretics. Practitioner, London, 18S9, 43: 270. A case in which collapse followed the ingestion of antipyrin. V. KoGERER. Antipvrinbehandlung des hektischen Fiebers. Wieu. klin. Wochenschr., 1SS9, 2: 778; 802. Out of 100 cases of phthisis in which antipyrin was given, erythema was noted in 2 instances and collapse in 1. The administration of antipyrin to the same patient on two occasions was followed by collapse. PuRDON, C. S. Intolerance of antipyrin. Brit. Med. J., Loudon, 1889, 1 : 1345. Man, 50, sciatica : A 5-grain dose of antipyrin was followed by severe nervous symptoms, cyanosis, and collapse. WiNGEAVE, T. Ill effects of antipyrin. Lancet, London, 1889, 2: 313. Woman, 21 : A dose of 10 grains of antipyrin was followed by dyspnea, loss of power on the left side, the appearance of an eruption, and symptoms of collapse. 1890. ScHWABE. Fall von akuter Antipyrinvergiftung. Deutsche Mecl.-Ztg., Berlin, 1890, 11: 501. Woman, 22, neuralgia : A dose of 15 grains of antipyrin was followed by dyspnea, complete blindness lasting thirty minutes, and symptoms of collapse. Spitzer, F. Selbstmordversuch mit Antipvrin. C'entrbl. ges. Therap., Wien, 1890, 8: 134. The ingestion of 2 drachms of antipyrin within an hour was followed by swelling of the face and eyelids and symptoms of collapse. 1S91. Watkjns. Pl. L. A case of antipyrine poisoning. New York Med. J., 1891, 51: 314. Woman, 30 : A dose of about 20 grains of antipyrin was followed l)y symptoms of cyanosis, collapse, and an eruption of white blotches. Tlie after effects lasted two months, during which time she suffered from weak- ness, palpitation of the heart, and an occasional reappearance of the eruption. 1S9S. GuTTMANN, p. TJeber einen Fall von Antii)vrin-Vergiftung. Therap. Monatsh., Berlin, 1892, 6: .560. The ingestion of 2.5 drachms of antipyrin, in 15 doses, twice daily, was followed by transient blindness, the appearance of an eruption, and symp- toms of collapse. 1S93. Krysinski, St. Przypadek otrucia antvpiryna. Gaz. lek., Warszawa, 1893 (2 s.), 13: 10.31. (Abs. Sajous, 1895, 5: A-3.3.) Girl, 20 : Ingestion of 81 grains of antipyrin was followed by symptoms of collapse. LITERATURE ON ANTIPYRIN POISONING. 69 Paterson, D. R. The untoward effects of autipyrin, ac-etanilide, and phenacetin. Practitioner, London, 1893, 51: 241. Several cases of antipyrin poisoning in which the symptoms were mainly those of cyanosis and collapse. TuRNBULL, L. A. Case of collapse caused by antipyrin. Meuiphis Med. Month., 1893, 13: 313. (1) Man, 52, acute articular rheumatism: After the second dose of 10 grains of antipyrin the patient became unconscious and passed into a state of collapse. (2) Woman: A dose of 10 grains of antipj'rin was fol- lowed by symptoms of collapse. Melville, S. Domestic drugging; a case of antipyrin ])oisoning. Lancet, Lon- don, 1894, 2: 1515. Ingestion of 30 grains of antipyrin within a few hours l)y a young woman was followed by collapse. 1800. Hayes, H. W. McC. A case of poisoning by antipyrin. P.rit. Med. ,1., London, 1896, 1: 209. Following the ingestion of 10 grains of antipyrin. the patient became cyanosed and passed into a condition of collapse. 1S07. p]iSENMANN, A. Ein Fail von Antipyrinvergiftung. Tlierai). Monatsh., Berlin, 1897, II: 233. •Youth, 20, headache: Ingestion of 7.5 grains of antipyrin was followed by dyspnea, a scarlatiniforni eruiition, cyanosis, and symptoms of collapse. Newton. I>. O. Notes on (wo cases of poisoning from antii)yrin. Quart. Med. J., Sheffield, 1897-98, 0: 133. (1) Man, 32: Took 10 grains of antipyrin for headache. Within two minutes he was seized with alarming symptoms— a feeling of suffocation, swelling of the face so that the eyes were closed, lachrymation, and dyspnea. The tongue was much swollen and the speech thick. There was no eruption. He was at work the next day with a slight swelling of the face. He had l)reviously suffered from a similar attack, probably caused, as in this instance, by antipyrin. (2) Woman, 54: Ten grains of antipyrin caused temporary blindness, unconsciousness, convulsions, and synii)toms of col- lapse. CASKS OF I'HOSTHATION. Under this heading are grouped the cases in which the systemic depre.ssion was very marked, but the symptoms were hardly severe enough to warrant classifying them under the term " collapse." 1884. TiLMAN, O. Antipyrin das neucsle Antii»yreticuni. I'.erlin, 1884. In two cases, one of j)hthisis and the otlier of ty|)hoid fever, (lie adminis- tration of antipyrin was followed by symptoms of marked depression. 70 ACETANILID, ANTIPYRIN, AND PHENACETIN. 18S5. Baeie, E. Note sur la valeur comparative de Tantipyrine et du sulfate de quinine, dans le traitement de la fievre typhoide. France med., Paris, 1885, 2: 1727. Two cases of typhoid fever in vphich the administration of antipyrin was followed by mild symptoms of collapse. Fedeli, C. Di alcuni fenomeni susseguiti all' uso dell'antipirina in un caso di febbre etica. Raccoglitore Med., Forli, 1885 (s. 4), 24: 414. Following the ingestion of antipyrin the patient's temperature rose to 106.6°, accompanied by chills and syncope. 1886. Johnson, R. Clinical observations on the action of antipyrin and thallin. Lancet, London, 1886, 2: 388. (1) Phthisis: Marked prostration followed the ingestion of antipyrin in three doses of 10, 20, and 20 grains, respectively. (2) Three 15-grain doses at intervals of one hour caused similar symptoms in a boy, with the addition of a scarlatiniform eruption. issr. GuTTMANN, P. Zwei Beobachtungen liber Nebenwirkungen des Antipyrin. Therap. Monatsh. Berlin, 1887, 1: 214. Report of two cases of antipyrin poisoning, one characterized by cyanosis and marked prostration, and the other by an itching eruption. Seifert, O. Ueber Antipyrin als Nervinum. Centrbl. kliu. Med., Leipzig, 1887, 8: 649. (1) Ingestion of 15 grains of antipyrin was followed by pains in the extremities, dizziness, and headache. (2) A dose of 15 grains of antipyrin given at 7 p. m. was followed by a severe buzzing in the ears, which prevented sleep for several hours. Weie, a. H. Dangers of antipyrin. Med. News, Philadelphia, 1887, 51 : 166. A dose of 7 grains of antipyrin was followed in five minutes by roaring in the ears, lachrymation, a burning sensation about the neck and face, precordial distress, and dyspnea. On another occasion 7 grains, and later, 3.5 grains, produced a similar train of symptoms, 18S8. Mayor, A. Abs., Brit. Med. J., London, 1888, 2: 787. Author states that he had repeatedly observed instances in which serious toxic symptoms followed the ingestion of antipyrin in doses as small as 7.5 grains. MoNOD, L. Accidents determines par I'absorption d'une faible dose d'antipyrine. Tribune med., Paris, 1888, 20: 113. A dose of 7.5 grains of antipyrin was followed by symptoms of coryza, dyspnea, aphonia, swelling of the eyelids, lachrymation, and general weak- ness, without fever or eruption. 1889. Beeger, H. Ueber einen Fall von Antipyrinintoxikation. Therap. Monatsh., Berlin, 1889, 3: 185. Ingestion of 15 grains of antipyrin by a patient 22 years of age was fol- lowed by dyspnea, palpitation, swelling of the face, profuse salivation, increased secretion of tears, and perspiration, and a feeling of paralysis which lasted for several days. LITERATURE ON ANTIPYRIN POISONING. 71 B.. H. The danger of antipyrin. Med. Rec, New York, ISS9, 36: 431. Woman, facial neuralgia : Thirty grains of antipyrin in three equal doses, six hours apart, caused marked prostration and convulsions. Feeny. M. H. Remarkable action of antipvrin in renal disease. Lancet, Lon- don, 1899, 2: 431. Two cases of renal disease in which antipyrin in 3-grain doses caused increased irregularity of heart and syncope. Hahn, F. Ein Fall von Antii>vrinexauthem. Centrlil. kiln. Med., Leipzig, 1880, 10: 849. Ingestion of 0.5 drachm of antipyrin was followed by dysphagia, cyanosis, and swelling of the lips. Erythema developed the next day. HucHABD, H. Contre-indications de Fantipyrine pendant la periode menstruelle. Rev. gen. clin. therap., Paris, 1SS9, 3: 52. Administration of 15 grains of antipyrin was followed by cyanosis and symptoms of depression. NoBTHRUP. W. P. A case of antipyrin poisoning. Med. News, Philadelphia, 18S9, 54: 4G1. The administration of 15 grains of antipyrin to a hysterical woman caused sneezing, vomiting, diarrhea, and marked prostration ; 5 grains caused sneezing, dyspnea, and an urticarial eruption. 1Q90. Mitchell, cited by Falk, E. Ueber Nebenwirknngen und Intoxicationen bei der Anwendung neuerer Arzneimittel. Therap. Monatsh., Berlin, 1890, 4: 97. The ingestion of 1 drachm of antipyrin in three doses at hourly intervals was followed by iiersistent vomiting and marked prostration. Young, E. W. Poisoning with antipyrin. Med. Rec. New York, 1890, 37: 409. Man, 43: A dose of grains of antipyrin with a teaspoonful of whisky aneech, and vomiting. lHf>.~i. LKwr.N. (;. I'.crl. kliii. VVochensciir., 1S!),5. 32: 727. (1) Antipyrin taken for beada<-h(! caus<'d cotivnlsioiis and (ii'lirinin. (2) 'I'lie iiigeHlion of antipyrin was followed by s»ivere dyspnea. 74 ACETANILTD, AFTIPYRIN, AND PHENACETIN. 1904. Dancourt, C. Un cas d'iutoxication profonde par ] 'usage immodere de Fanti- pyrine. Nord. med., Lille, 1904, 10: 89. Patient, 55 : Habitual use of 0.5 drachm of autipyrin daily liad a detri- mental effect upon the nervous system, causing abolition of the reflexes and slight paralysis. MOUTH SYMPTOMS. In these cases the toxic symptoms were exhibited chiefly by the mucous membrane of the mouth. There was, in most instances, a burning, prickling sensation, w^hich was followed by swelling and the development of small blisters upon the tongue, inside of the cheeks or gums, with subsequent ulceration. In most cases the ulcers healed kindly. In one of the cases a number of abscesses formed in the mouth. X8S9. Bourns, D. C. G. Unusual effects of antipyrin. Brit. Med. J., London, 1889, 2: 818. A dose of 20 grains of antipyrin was followed by cyanosis of the lips, swelling of the tongue, and the development of small ulcers within the mouth. X890. Salingkr, .J. L. A case of antipyrine poisoning, with the formation of mem- branes in the mouth, and symptoms of Laryngismus stridulus. Amer. J. Med. Sci., Philadelphia, 1890 (n. s.), 99: 489. Woman, 53 : A dose of 5 grains of antipyrin was followed by dyspnea, an urticarial eruption, swelling of the lips and tongue, coma, and symptoms of collapse. On the third day a white membrane formed upon the tongue, lips, and pharynx, and soon after 13 abscesses the size of a chestnut or smaller developed in the mouth. Ou two subsequent occasions the ingestion of 5 grains of the drug was followed by similar symptoms. 1S91. Veiel. Ein seltener Fall von Blasenausschlag in Folge von Antipyrin. Arch. Dermat. Syph., Wien, 1891, 23: 33. Man, 33, headache: Ingestion of 15 grains of antipyrin was followed by itching of the palms and soles, swelling of the lips, and the formation of blisters in the mouth. Similar symptoms appeared whenever the patient took antipyrin. 1893. GouKiN, E. Des accidents dus a I'antipyrine. Paris, 1893, p. 59. Ingestion of 15 grains of antipyrin was followed by swelling and ulcera- tion within the mouth. 1894. Beasch, M. Zum Capitel der Antipyrinexantheme. Therap, Monatsh., Berlin, 1894, 8: 565. Ingestion of 30 grains of antipyrin was on four occasions followed by swelling of the lip with the formation of blisters and the appearance of white plaques on the tongue. LITERATURE ON ANTIPYRIN POISONING. 75 1895. Senator. Berl. klin. Wochenschr., 1895, 32: 727. Girl, 16 : Ingestion of 4.5 grains of antipyriu within three days was fol- lowed by a burning sensation in the eye, mouth, tongue, and pharynx, and the appearance of vesicles. At the Siiuie time au urticarial eruption de- veloped upon the body. IBOO. Dalciie. r. Accidents causes par I'antipyrine. Rtomatite ulcero-membraneuse. Bui. mem. soc. med. hop.. Paris, 1X90 (3 s.), 13: 704. Man, 26 : A dose of 15 grains of antipyriu resulted in the appearance of vesicles in the mouth followed by ulceration. Steinhardt. Idiosynkrasie gegen Antipvrin. Therap. Monatsh., Berlin, 1896, 10: 629. The ingestion of 15 grains of antipyriu was followed by swelling of the lower lip and the development of ulcers within the mouth. 1897-. Lyon. Dermatitis et stomatitis pemphigoides dues Ti I'antipvrine. Med. mod., Paris. 1897, 8: 167. Woman, .32 : The ingestion of 15 grains of antipyriu was followed by the appearance of a pemphigoid eruption around the knee and elbow. There was also an eruption upon the mucous membrane of the mouth. 189«. Immerwahr. R. Ein Fall von Antipyrinintoxication. Berl. klin. Wochenschr., 1898, 35: 751. On two occasions the ingestion of 0.5 grain of antipyriu was followed by the appearance of vesicles within the mouth. Martyn, G. K. Stomatitis following the administration of antipyriu. Brit. Med. J.. London, 1898, 2 : 807. Ingestion of antipyriu was followed by the appearance of patches of superficial stomatitis. 1899. Delobel. Stomato-GIossite herpetiforme consecutive a I'absorption d'anti- pyrine. J. sci. med. Lille, 1891>, 1 : 25. After taking .30 grains of antipyrin, and again after 15 grains, the patient suflfered from an eruption of herpetic vesicles in the mouth. lOO.'J. Leredde kt I'at'trier, L. I-^tude experinicntale d'une eruption medicamenteuse, due Jl raiitipyrine; existence de lesiims sanguines. Compt. rend. soc. l)iol., Paris, 1903. 55: 910. The ingestion of 3 grains of jiiilipyrin was followed by pruritus of the genital organs, an urticarial ('rui)tion. nasal catarrh, and patches in the mouth and upon the lips. lJ»r).'->. LOEBI,, II. Seltene Lokalisafion cines Aiitipyrincxantlieiiis. Med. Itl., WIen, 19(J.5, 28: 31.5. Following the Ingestion of anlipyrin tbf iiilcrior of tin- inoutli bt-came covered with small blisters, which burst, giving rise to coiilluent ulceratiou. 76 ACETANILID, ANTIPYRIN, AND PHENACETIN. 1906. Levin, E. Zur Kenntniss der Migrjininvergiftnng. Berl. kiln. Wochensclir., 1906, 43: 766. Ingestion of 15 grains of migrainine was followed by swelling and ulcera- tion of the mucous membranes of the mouth and profuse salivation. EYE SYMPTOMS. Under this heading are included the cases in which the acuity of vision was diminished or the sight temporarily lost, and also the cases characterized by the symptoms of coryza, with swelling of the lids,^ lachrymation, and, in some instances, photophobia. The symptoms in most cases appeared promptly, sometimes, it seemed, almost as soon as the drug reached the stomach. 1906. HoTz, F. C. A case of autipyrin amaurosis induced by one hundred and thirty grains taken in forty-eight hours. Arch. Ophth., New York, 1906, 35 : 160. Man, 33 : Had taken antipyretics for pain for three years. One hundred and thirty grains of antipyrin within forty-eight hours caused his sight to become dim, and within two days it was lost completely. It returned slowly and in two months he was practically well again. Inouye, M. Antipyrin keratitis. Ophthalmol., Milwaukee, 1905-6, 2: 618. Woman, 48 : Ingestion of 25 grains of antipyrin in 2 doses was followed by the development of 41 superficial infiltrations upon the cornea, 25 upon the right and 16 upon the left. The author also reviews a case reported by Mizno,* in which ulcers developed upon the cornea as a result of the ingestion of antipyrin. GENITO-URINARY SYMPTOMS. Under this head are grouped the cases in which the toxic effects of antipyrin were exhibited chiefly in some part of the genito-urinary tract. The symptoms presented were principally albuminuria, sup- pression or incontinence of urine, or symptoms of urethro- cystitis. 18S4. MtJLLER, F. Beobachtungen iiber Antipyrin. Centrbl. klin. Med.. Leipzig, 1884, 5: 569. Drowsiness and involuntary micturition appeared in two cases after the ingestion of antipyrin. 1S85. Haven, H. C. Discussion of Mason's paper. (1885.) p. 538. Infant : Ingestion of at least four 10-grain doses of antipyrin at inter- vals of half an hour caused vomiting and complete suppression of urine for over twenty-four hours. " Nihon-Gankwa-Gakkwai-Zasshi, 1904, vol. S, No. 11. LITERATURE ON ANTIPYRIX POISONING. 77 1887. DE TuLLio, P. L'antipiriiia iiel reuiiiatisiuo i;rticoIan> acuto. Prosresso iiied Napoli, 1887, 1 : 913. The ingestion uf antipyriii liy a juitieiit snflferiug from articular rheiinia- tisiu was followed by a Iransieiit alhmiiiiuiria. 1888. KouLiN, L. Observation d'accideuts febriles produits i)ar raiitii)yrine. liiil. mem. see. nied. prat., Paris, 1888, p. 478. Ingestion of 7.5 grains of antipyrin hourly for four hours was followed by a severe chill, delirium, vomiting, and suppression of the urine. 1801. Biggs. H. M. Notes on a case of poisoning l)v antipyriue. New York Med. J., 1891, 53 : 35. Man, 35, headache: Soon after the ingestion of 60 grains of antipyrin within thirty hours the urine became darii olive-green in color. It con- tained a small quantity of albumin and a few casts. Secretion scanty. Symptoms disappeared in the course of two or three days. No evidence of previous renal disease. Tompkins. E. I.. Albuminuria caused bv antipyriue. Virginia Med. Month., Richmond, 1S91-92, 18: 105. Man, locomotor ataxia : Took for pain each night about GO grains of antipyrin. Entered the hospital with edema of the legs and eyelids. Tlie urine was so full of albumin that it solidified on boiling. Albumin was abundant in the morning and scanty in the evening. When the drug was discontinued the albuminuria disappeared and the edema diminished. 1895. IvAMOs, D. All)uminui-ia produ/.ida por altas doses de autii)yrina. Hrazil-med., ' Kio de Janeiro, 189.5. »: 233. i8or. Spanoudls. .1 Dangers de ranliiiyriue dans Ferysipele. Seuiaiue uied., I'aris, 1SU7, 17- 42. Three cases in wliich the ingestion of antit)yrin was followed by anuria, with great restlessness and marlied depression. One case tcnuinated in death. 1808. " liKSMKK. liMl. soc. franc, dermat. syph., Paris, 1898, 0: 193. An lntens«' general urticaria followed the ingestion (tf anlipyriu, and an autifiyrin tampon inserted for er>istaxis caused vesication and symptoms of nrethn»-cystitis. SYMPTOMS OK COKYZA. 1888. 'J'avi.ok, II. c;. Idiosyncrasy to autipyriu. J'>rit. .Med. .1.. Loudon, 1S8S, 1 : (»9.5. Woman, lieadache: On two occasions the iugeslion of autipyriu was Col lowed by symi»tomH of coryza and severe paroxysms of cougiiiiig. 78 ACETAN'ILID, ANTIPYEIN, AND PHEN-ACETIN. 1897. Geoll et Meuniee. Intoxication par I'antiprine. Daupliine med., Grenoble, 1897, 21: 38. The ingestion of 22.5 grains of antipyrin was followed by symptoms of coryza. 1903. AxBABEL, Accidents dus a I'antipyrine. Rev. gen. clin. tlaerap., Paris, 1903, 17: 612. On two occasions tlie ingestion of a 7.5-grain dose of antipyrin was fol- lowed by coughing, burning, and dryness within the mouth, and symptoms of severe coryza. 3IISCELLANEOUS. 1888. Brandenberg, F. Nebenwirkung des Antipyrins. Cor.-Bl., f. schweiz. Aerzte, 1888, 18: 611. Man, acute articular rheumatism : Ingestion of 1.5 grains of antipyrin was almost immediately followed by odontalgia, severe otitis, and lachry- matiou. On another occasion one-half of the above dose produced similar symptoms. 1889. TiTCZEK, F. Schwere Antipvrinvergiftung bei einem Kinde. (Antipyrinepi- lepsie.) Berl. klin. Wochenschr., 1SS9, 26: 373. Boy, 4, whooping cough : Antipyrin, 18 grains in 3 doses daily for three weeks, was followed by vomiting, drowsiness passing into coma, convul- sions, and the appearance of a macular erj'thema. 1890. DuFFUs, J. C. G. Parotitis caused by antipvrin. Brit. Med. J., London, 1890, 2: 733. Young woman, influenza : A dose of 10 grains of antipyrin was followed by dyspnea and swelling of the parotid glands. 1891. CoMBEMALE. I'n cas d'autipvrinisme chronique. Bui. med. nord, Lille, 1891, 30: 304. A case of persistent use of antipyrin in which the patient took from 15 to 30 grains daily for four years. Verneuil. Gangrene partielle du pied, consecutive a des injections hypoder- miques d'antipyrine. Bui, acad. med., Paris, 1891 (3. s.), 26: 602. Man, 39. neuralgia : Gangrene followed the hypodermic injection of antipyrin. 1893. Cappelletti, L. Un caso di autipirinomania. Riv. sper. di freniat., Reggio- Emilia, 1893, 19: 100. Mania for antipyrin in a neurotic girl aged 23. Took small doses for headache, and gradually increased the amount up to 2 drachms daily, causing increase in the severity of the headach.es, anorexia, hysterical convulsions, and symptoms of depression. LITERATURE ON PHENACETIN POISONING. 79 1S95 . Gonzalez y Campo, J. Iiuoxicacion por la aiitipirina a tlosis terapeutica. Rev. de med. y cirug. pnict., Madrid, 1895, 36: 201). Case in wliicli the poisonous effects of antipyriii may have l)t'en brought about by a cumulative action due to impei-fect elimination. 1S97-. Papillox, (;. E. Note sur iiii cas rare de dermatoneuroso consr^cutive i\ I'ingestiun d'antipyrine. Echo med. nord, Lille, 1S97, 1 : 97. Girl, 19: Habitual use of antipyrin. Gradually increased the amount until she was taking from 1 to 1.5 drachms daily. The symptoms resem- bled those of ulcer of the stomach. ACETPHENETIDIN (PHENACETINi. INTUODUCTOKY RESl MK. Following is a list of the recorded cases of poisoning by acetphe- netidin (phenacetin) from 1887 to the close of the year 1907, with a brief abstract of each case. During this period 70 or more cases were reported by 41 observers. As already stated, it is practically impossible to determine the number of the cases with accuracy, owing to the indefinite character of some of the reports. Of the total num- ber of cases, 3, or 4.2 per cent, are reported to have terminated fatally. This number, 70, is notably less than the reported number of cases of poisoning by either acetanilid or antipyrin, and this fact tends to sub- stantiate the common belief that of the three drugs acetphenetidin is, under ordinary circumstances, the least liable to produce ill effects. The number of cases of poisoning reported in each year since the introduction of acetphenetidin as a remedial agent, together with the number of observers, is shown in the following table: Caxr-f of tiff'tj/lif'nrtiilin (phenacetin) poi-sonhnj rcportrd 7.1 [)er cent, wei'c r('j)ort<'(l (hiring (he years 1888, 1889, and 1890. Tlie large proporlion of cases reported during this period was undoubtedly due in part, as in case of acetanilid aiul antipyrin, to the fart that at this time the depressing effect of ncvl- 80 ACETANILID, ANTIPYRIN, AND PHENACETIN. phenetidin was not fully appreciated, and it was administered more or less freely in asthenic as well as sthenic affections. This method of administration resulted in the production of ill effects in not a few cases. After the year 1890 the number of cases of poisoning reported annually was, upon the average, only two or three cases, and the number appears to have decreased rather than increased as the years passed. The ill effect which appears to occupy the place of greatest im- portance in the recorded cases is general systemic depression. This symptom appears to have been present in 27, or 38.5 per cent, of the cases. In 12 cases, or 17.1 per cent, it amounted to actual collapse, and in 15, or 21.4 per cent, it was present in a milder form. Cyanosis was reported in 34.3 per cent of the cases, and the comparatively^ fre- quent occurrence of this sjanptom indicates the close pharmacological relationship which exists between acetphenetidin and acetanilid. Skin affections of various kinds were noted in 30 per cent of the cases, dyspnea in 14.3 per cent, and disturbances of the functions of the kid- neys in 10 per cent. ABSTRACTS OF ACETPHENETIDIN (PHENACETIN) CASES. ISST". KoBLER, a. Das Acetphenetidin als Antipyretic-nm. Wien. uied. AVochensclir., 1887, 37: 868. In a pMhisica] patient two doses of phenacetin of 4.5 grains each within two hours caused the patient's temperature to fall rapidly to 95° in the rectum, with profuse perspiration and a feeling of chilliness. ISSS. Cakslaw, J. H. Phenacetine as an antipyretic. Glasgow Med. J., 1888, 30: 64. A single dose of 5 grains of phenacetin caused collapse in three out of five tubercular patients to whom the drug was administered. Cattani, G. La fenacetina. Gazz. med. ital. lomb., Milano, 1888, 48 (9 s. vol. 1) : 455. The author had twice observed hematuria and nephritis following the ingestion of phenacetin. Pie had also observed an acne-like eruption. HoppE, H. Ueber die Wirkung des Phenacetin. Therap. Monatsh., Berlin, 1888, 2: 160. (1) Anemic girl took 19 grains of phenacetin, and after four hours a second powder. This was followed bj' dizziness, shivering, yawning, chilli- ness, blueness of the nails, and some nausea. (2) Woman, 44: The in- gestion of 15 grains of phenacetin for headache was followed by chills and dizziness. (3) Thirty grains of the drug taken by a healthy student were followed by persistent yawning, nausea, insomnia, general weakness, feeble pulse, and inability to stand. The symptoms lasted for three hours. (4) Woman, 26: The ingestion »of 15 grains of phenacetin for headache was followed in fifteen minutes by chilliness, coldness of the extremities, severe palpitation, and a sensation of intense fear. The symptoms passed off after six hours. LITERATURE OX PHEXACETIX POISOXIXG. 81 V. Jaksch, R. Ueber die neiieivn Antipyretica und iiite Wiikun-r am Krar.kcn- bette. Tlierap. Mouatsh., Berliu, 1888, 2: 189. Author had observed that the adnimistration of 1.5 to 3 grains of phe- nacetiu to children iu a nuuiber of cases produced profuse sweating, severe cyanosis, and even symptoms of collapse. LiXDMAXX. T'nangenehnie, bedrohlicbe Xebenwirkuugen des Phenaoetiu. Therap. Monatsh. Berlin, 1888, 2: 3UT. Woman, .34 : Soon after taking l.^> grains of phenacetin she felt dizzy, cold, and nauseated. Her headache became worse, and after three hours she took another phenacetin powder. This was followed by an aggravation of the symptoms: the nausea and sensation of chilliness increased, the hands, lips, and cheek.s were deep blue, and there was cold perspiration and dyspnea. Mahxert, F. T'eber Phenacetin voni klinisrhen und physiologischen vStand- r>unkte. Deutsche med. Wochenschr., Leipzig, 1888, l4: 10.51. A nervous woman, after taking lo.o grains of phenacetin for headache, developed a well-marked urticaria on the face and chest. >L\sirs. Contribution tl Tetude de proprietes therapeutiques de la phenacetine. Bull. acad. roy. med. belg., Bruxelles, 18SS (4 s.). 2: 81.5. (1) Girl, 10, typhoid: Was given 7.5 grains of phenacetin at 3 and at 8 o'clock a. m. About an hour after the second dose she comi)lained of thor- acic oppression, a sensation of intense heat, marked prostration, and deep cyanosis. The cyanosis passed off on the following day. On the preceding day the patient had taken 30 grains of phenacetin without ill effect. (2) (iirl. 1.5. typhoid: Five hours after taking two doses of phenacetin of 3.75 grains each the patient's tenipei'ature rose raiiidly with a severe chill. There was also slight cyanosis of the extremities. (3) Woman, 24: The Ingestion of three doses of phenacetin of 7.5 grains each was followed after four hours by a severe chill and cyanosis of the lips and skin around the eyes. (4 and 5) In two instances the ingestion of phenacetin by tubercular patients produced ill effects, principally chills and cyanosis. In one case the dose was 15 grains, and in the other (j grains. MuxLEB, F. Ueber Acetphenetidiu. Therap. Monatsh., Berlin, 1888, 2: 355. Author observed cyanosis and methemoglobinuria in two patients who were taking from 1.5 to 2 drachms of phenacetin daily. RuMPF. Ueber das Phenacetin. Berl. klin. Wochenschr., 1888, 25: 45!» The ingestion of 15 grains of phenacetin was followed on several succes- sive days by a feeling of thoracic oppression and slight dyspnea. Valextix. a. Ein Fall von Phenacetinexanthem. Therap. Monatsli.. P.erliii. 1S88, 2: :j;jo. Two hours after taking a dose of 15 grains of phenacetin the patient felt a sensation of heat and i>y the next day the entire skin was covered witli red HiKjts. The eruption was especially markem s. k. konlriir vcrkan iif fcbfiiin-dcl. i psaia L;ik:n( .' Forh., 1S.H8-80, 24: 203. Author observed in a patient a rise nf tfinpi-i'atinc after llif adiiiiiiisi lii- tlon of phenacetin. 82.311)— P.ull. 12!V— 0!) 82 ■ ACETANILID, ANTIPYEIN, AND PHENACETIN. HiRSCHFELDER, L. Beiti'ag zur Wirkuug ties Plieuacetius. Deiitsches Arch, kliu. Med., Leipzig, 1S88-89, 44: 434. The ingestion of pheuacetin was followed by the appearance of red con- fluent macules, accompanied by a sensation of burning and prickling. The symptoms disappeared on the following day. HoLLOPETER. W. C. Phenacetiue poisoning. Med. News, Philadelphia, 1889, 55: 335. Woman, 30 : Took three doses of pheuacetin of 7.5 grains each within six hours. She passed into a state of collapse, with severe precordial pain, great dyspnea, lividity of the skin, and great restlessness. The cyanosis persisted for three days. HoRVATH, A. A'datok a pheuacetin hetasahoz. Orvosi hetil., Budapest. 1889, 33: 474. (Abs. Pest, med.-chir. Presse, Budapest, 1889, 25: 1134.) Report of two cases in which the use of pheuacetin was followea by an eruption upon the skin. Oeffinger. Eine eigenthiimliche Nebenwirkung des Pheuacetin. Aerztl. Mitth. Baden, Karlsruhe, 1889, 43: 110. The ingestion of 30 grains of pheuacetin in two doses with an interval of three hours caused edema of the lower eyelids. A few days later 45 grains in three doses caused edema of the face and fingers. Tripold, F. Ueber die therapeutische Wirkung des Pheuacetin und Thalliu. Wien. klin. Wochenschr., 1889, 2 : 151, 178. Author states that in his experience doses of 4.5 grains of pheuacetin had produced deep cyanosis of the face and hands and profuse perspiration in children suffering from tuberculosis. In a case of pneumonia a dose of 4.5 grains caused severe collapse, with cyanosis. Even 3 grains caused chills, collapse, and cyanosis in two cases in children. 1890. CoLLiscHONN. Pheuacetin als Antirheumaticum. Deutsche med. Wochenschr., Leipzig, 1890, 16: 97. The ingestion of phenacetiu was followed by repeated vomiting, so that the administration of the drug had to be stopped. RiFAT. Traitement du rhumatisme aigu et biennorrhagique par la phenac^tine k haute dose. Bui. gen. therap. (etc.), Paris, 1890, 118: 410. (1 and 2) In two cases pneumonia and tuberculosis, respectively, doses of 4.5 grains of pheuacetin caused profuse perspiration, a tendency to syncope, and great restlessness. (3) In a case of typhoid fever, cyanosis followed the administration of. large doses of pheuacetin. (4) Woman, 65, articular rheumatism, with arteriosclerosis : The ingestion of 75 grains of pheuacetin daily was followed on the fourth day by the appearance of uremic symptoms. There were vomiting, severe dyspnea, fear, and almost complete suppression of the urine. Ubaldi, a. Suir aumento dell'acido solforico accoppiato nelle urine in seguito alia somministrazione di fenacetina. Azione tossica della fenacetina. Riforma med., Napoli, 1890, 6 (1) : 752. 1891. Demme. Ueber die Wirkung und Dosirung der hauptsachlisten neueren Anti- pyretica, mit Beziehung auf das Kindesalter. Therap. Monatsh., Berlin, 1891, 5: 160. Author had observed an eruption resembling that of measles, and cya- nosis of the cheeks and mucous membranes in children after the use of pheuacetin. LITERATURE OX PHEXACETIX POISONING. 83 Hare. H. A. Fever: Its pathology and tie:ituient by .iiitiiiyretics. ISOI. Phila- delphia aud Loudou, p. 122. The author mentions two eases in which the ingestion of H-grain doses of phenacetin was followed by the aiipearante upon the skin of large wheals, like those observed in urticaria. Fernandez de Ibarra. A. M. In caso de envenenauiiento eon fenacetina ; curacion. Gao. uied. catal.. Barcelona, 1892, 15: 229. TiNGLEY. W. K. Peculiar vasomotor disturbance after the administration of phenacetlue. Med. Rec, New York. 1X92, 42: .341. The author had observed three cases with almost identical symptoms. In each of them phenacetin alone i»roduced no disturbance, but if champagne were taken in addition, even after the lapse of some hours, the patient's face became flushed, the eyes suffused, and the conjunctiva bright red. White spots appeared irregularly over the neck, face, and chest, and vertigo was present. Whisky, brandy, and claret alone did not produce these effects. 1893. Illoway, H. Does phenacetin possess convulsivant jiroperties? Meeen addicted to the phenacetin hai)it for about seven months, daily quantity being between lij and 20 grain.s. Addiction was discovered by her husband when her supply of the drug gave out and the local pharmacist also ran out of a su[iply temporarily. Violent convulsive and hysterical seizures followed and continued until phenacetin was secured for her. Pulse. 170, and very weak. Resjiiration, .30, spasmodic. Pnr)lls widely dilated; pallor, cold i»erspirafion. She had more than a dozen con- vulsions and vomit«'d freely. P.eforc beginning the habit she was "a healthy, buxom conniry girl." Kxaniination made after llic !i1ta<-k above dewribed showed some anemia, compl'-xioii bad. circulation weak, pulse 124, restlesH and ti'oublcd sleep, impaired digest ion. occasional vertigo. 84 ACETANILID, ANTIPYRIN, AND PHENACETHST. Cekna, D. Plienacetiu as a toxic agent. Tr. Texas Med. Assoc, Galveston, 1895, p. 126. Infant, 5 days old, was given seven 2-grain phenacetin powders witliin two days. It became fretful, weak, and eyanosed. On the next day the conjunctiva was jaundiced, the skin eyanosed, and the child very restless. On the day following there was extreme cyanosis, and bloody urine was passed in large quantity. Kronig, G. Phenacetin-Yergiftung mit todtlichem Ausgang. Berl. klin. Wochensehr., 1S95, 32: 99S. Boy, IT : After taking 15-grain doses of phenacetin for headache for three weeks, a dose caused vomiting, followed on the next day by prostra- tion, cyanosis of the face, weak pulse, and diarrhea. Jaundice followed, and the cyanosis spread to the extremities. The urine consisted of almost pure blood. Death occurred, after two days, from methemoglobinemia. Lackie, J. L. Note on phenacetin as causing dyspnoea and orthopucea. Med. Press and Circ, London, 1S95, 60 : 208. (1) Dyspnea and great restlessness followed the ingestion of phenacetin everj- two hours in 15-grain doses. (2) The ingestion of 20 grains of phenacetin every two hours caused marked dyspnea, which lasted for one hour. West, R. M. Two cases of phenacetin rash. Lancet, London, 1895, 1 : 91. (1) Ingestion of two 5-grain tabloids of phenacetin by a man 28 years of age was followed in three hours by the appearance of a scarlatiuiform rash upon the face, chest, and arms. It disappeared in two hours. (2) A young woman took phenacetin in doses of from 5 to 15 grains for neuralgia. On each occasion an urticarial rash appeared, chiefly upon the face and neck, after a lapse of one or two hours. 1896. Betts, W. a. a case of phenacetin idiosyncrasy. Brit. Med. .!., London, 1896, . 1: 146. Patient took 8 grains of phenacetin every three hours for headache. After the third dose he felt very ill, and his face became pale. This was followed by shivering, dyspnea, cold perspiration, and the development of wheals on the back of the hands and on the right shoulder. The face was of a mahogany color and swollen. Dread of death. Recovery. 1S99. Gtjleke, H. Taubheit in Folge von Phenaeetinmissbrauch. Zts. prakt. Aerzte, Frankfurt, 1899, 8: 765. Male, 48 : Ingestion of 10.5 grains of phenacetin every two hours until 10 doses had been taken caused cyanosis and complete deafness. 1901^ KiBBE, M. E. Ecchymotic spots and pruritus due to phenacetin. Occidental Med. Times, San Francisco, 1901, 15: 371. Woman, 50 : Ingestion of six 5-grain powders of phenacetin during the evening and morning caused itching of skin over abdomen and limbs. On the fourth day large areas of ecchymosis appeared on the inner surface of each thigh, and smaller ones on the abdomen and extensor surfaces. LITERATURE OX PHEXACETIN POISONING. 85 1903, White. A. T. A case of acute dysentery, in which deatii occurred from acute cardiac dilatation probably due to chronic phenacetin poisoning. J. Trop. Med.. London. 100.3. 6: 176. The increstion of about .3.000 grains of phenacetin in H-grain doses within sixty days for fever was accouii)anied by great depression and a rapid dihition of the heart followed by death. The result may fairly be attrib- uted to the inordinate use of the dru.g. 1004. Laurexce. S. M. Case of poisoning bv phenacetin and antikannrla. P.rit. Med. .J.. London. 1004. 1: 545. The ingestion of 75 grains each of phenacetin and antikanniia was fol- lowed by vomiting and malaise. The face became pinched and pale, and the expression anxious. The eyes were small and the lips and fingers purple, ^larked prostration with cold perspiration. LoBL, V. Aspirin-('-s phenacetinmergezesek. (Aspirin and phenacetin poison- ing.) Budapest! orv. u.isrig.. 1004. 2: 803. HiRSCHFELD, M. Eiu Fall von chronischer Phenacetin-Vergiftung. Deutsche med. Wocheuschr., Leipzig, 1005, 31: 66. The ingestion of phenacetin for headache was followed by the appearance of an eruption of petechial spots upon the legs, followed in the cour.se of a week by ulceration. The ulcers healed rapidly when the drug was dis- continued, and appeared again after another dose of 22.5 grains. Meurice, J. Contribution a I'etude de la toxicite de la phenacetine. Ann soc. de med. de Gaud., 1905, 85: 199. The ingestion of 15 grains of phenacetin every two hours for twenty-four hours was followed by great weakness and then symptoms of collapse, with tendency to syncope, vertigo, dyspnea, cyanosis of the extremities, precordial pain, nausea, and rapid and feeble pulse. The skin was of a yellowish-gray color, and on the next day there appeared a macular erythema. Recovery after five days. 10()7. ToBEV. rjEORfjE L. Fatal i)oisoiiing by pjienacetin in headache tablets. Monthly Bulletin of the State Board of Health of .Massachusetts, January. lOOS. On Friday. December 13. 1907. at 0.20 j). m., a girl of 16.5 years, in good general health, but having a headache and feeling that she had taken cold, tr)ok 2 headache tablets and went to bed. Later, her mother heard her coughing and went to her. There was nothing at this time to cause alarm, but a little before 11 o'clock the girl's lips and face began to become blue, and in consef^uence a physician was sent for. He resi)onded at once, and found the girl with great weakness of the heart and edema of the lungs. Before he could administer any remedy she was dead. 'I'he box with tin; remaining tablets was sent to the olfice of the state board of health fr)r examination. The tablets were found to contain phenacetin. The box was labeled " Daubury's Headache Tablets." o COLUMBIA UNIVERSITY LIBRARIES This book is due on the date indicated below, or at the expiration of a definite period after the date of borrowing, as provided by the library rules or by special arrangement with the Librarian in charge. DATE BORROWED DATE DUE DATE BORROWED DATE DUE ■, v -jvt ,_ »■ ■% '\ CZa( 10-53) lOOM PAM PHLET BINDER — •- Syracuse, N. Y. — ^;^ Sfockton, Calif. Kebler QP971 K23 1909 The harmful effects of acetanilid antipyrm, and phenacetin. 1 W 19 1955 C,U. Jil