REMARKS ON THE THERAPEUTIC USES AND EFFECTS OF ANTI PYRIN. By Surgeon PATRICK
IIEHIR,
m.d., f.r.c.s.e.
Antipyrin,
known to pharmocologists by overwhelming and impracticable name of Dimethyloxyquinizine, is the term originally
the
the proprietors and discoverers to one of the most popular antithermic remedies that have been introduced into our pharmacopoeia within recent years. It is an alkaloid, synthetically prepared from chinolin, Although the name given to this drug expresses the most significant of its therapeutic properties, it is now a well-known fact that to limit its employment to the reduction of febrile temperature would be considerably curtailing its sphere of usefulness. Whilst we cannot be too lavish in our praises of those excellent workers by whose indefatigable efforts our defensive agents against disease are being constantly enriched, we cannot lose sight of the fact that it frequently happens that in the original announcement of the discovery and description of a new drug, the enthusiasm of the discoverer often leads him to over-estimate the therapeutic properties of the new-born remedy, and thereby tends to cast discredit on those virtues which the drug actually possesses, or the drug rapidly rises in popularity on account of the eulogistic terms in which it is represented to the profession. So it was with antipyrin, early after its discovery by Knorr, and the first inquiry as to its uses in clinical medicine by Filchne (who rather under-rated or at least limited its therapeutic value), the number of investigations rapidly increased, and within a few years the published literature on the subject of its therapeutic applicability became enormous. It was considered by some to be a sort of panacea, a universal specific. But happily for the profession we have other diligent labourers constantly engaged in rectifying such discrepancies as these, men whom experience has taught to sift the wheat from the chaff, and who soon advise us as to the special benefits to be derived from all newly discovered remedies,and cautiou us where care and discretion are demanded. But antipyrin is not accepted by all as an unalloyed boon. From many quarters one finds attempts made to depreciate its use, and I am convinced that amongst certain physicians at least, and these men of high standing in the profession, there is at the present day a prejudice against the use of all the more receutly discovered antipyretics, especially those of the
given by
0
?
t
Oct.
1891.]
HEHIR ON ANTIPYRIN.
coal-tar derivatives, claiming that the depressant action of such drugs in the febrile state is
for alarm than the condition they intended to antagonise. But in the case of antipyrin this is an extreme view, and holds good only with regard to what might be considered poisonous doses. There is now overwhelming evidence to the effect that the practitioner who entirely sets his face against the use of antipyrin robs himself of one of his most powerful auxiliaries in many cases, and he does so to the detriment of his patients. In antipyrin we, doubtless, have a potent agency, but there is no more reason that we should use it without care and discretion than that we should use morphine in toxic doses where smaller ones will effect the desired end. It has surely never been conceived that because a one-grain dose of morphine or strychnine frequently repeated would quickly prove fatal, therefore lesser doses are not to be used in any case. If it be contended that the smaller doses of antipyrin frequently repeated do not act so efficiently as the larger doses given at longer intervals, I, with all due deference, express a contrary view, and have many high authorities to support me in this opinion. Notwithstanding the volumes of adverse criticism to which this drug has been subjected it has gained ground, and as far as its use in the treatment of certain diseases and symptoms are concerned, its position has been established. The differences of opinion expressed by different authorities regarding the drug are in a measure explained by the difference in the quantity administered at each dose, or over a given time. In a number of standard works, "we find doses of 20, 30, and even 60 grains advocated, the dose differing, of course, in accordance with the reason for which it is administered. The dose advised in pyrexia! states by Lauder Brunton is 30 grains repeated three times, by Ringer 20 to 60 grains, by Barthelow 10 to 60 grains, and by Waring 20 to 30 grains every hour, for four doses. The use of such large doses as an orthodox practice would, I think, in India be fraught with the utmost danWe are acquainted with one case, at least, ger. in which an aggregate of 80 grains taken in three hours proved fatal. Personally I am convinced that in this climate as a rule the maximum dose of 10 to 15 grains should not be exceeded, and that even this quantity should not be frequently repeated except under extreme circumstances, e. g., when the antipyretic action of the drug is demanded without delay. I usually give it in hourly doses of 10 grains repeiited for 5 or 6 doses according to the effect required, or half hourly doses of 5 grains to reach the same quantity. In children, when necessary, f of a grain for every year of age is prescribed hourly. I have prescribed it successfully in more a cause are
293
accordance with this method in pyrexial states in in all ages, even in the case of a new-born infant; and I have never witnessed any of the serious effects described by some authorities, although we sometimes have been obliged to discontinue its use, especially in the case of children. In prescribing it for these latter, it is necessary to watch the effects carefully. It is a very convenient remedy, and has some general advantages appertaining to its use, amongst which are, its ready solubility iu water; it is not unpleasant to the taste, rarely irritates the stomach, and it rapidly diffuses into the blood. It occasionally produces an eruption like that of measles, which appears on the trunk chiefly, but never on the face. We have frequently seen it produce a passing erythematous blush. On two occasions it produced a large vesiculo-pustular eruption, and on one an urticarial rash without the irritation, however, of ordinary urticaria. It is said that large It doses sometimes cause hasmoglobinuria. may be given in various ways?in solution, in tabloids, cachets, wafer enclosed in paper,
hypodermically,
or
as a
deep-seated injection.
These latter we have found to give some pain as a rule, which might be relieved either by combining the solution with ? grain morphiue For hypoor a similar quantity of cocaine. dermic use 10 grains are dissolved in 10 minims of hot water, and allowed to cool before using. We may now pass on to consider its use iu certain diseases and symptoms beginning with those in which the drug is employed tor its
antipyretic properties.
few years ago our therapeutic resources the more severe forms of pyrexia were limited to quinine, salacin, aud its salts, and cold water, but at the present day we suffer from an embarras de richesses in relation to antipyretic remedies, the physician, if he is disposed to use such agents being sometimes puzzled as to which of the many fever-reducing drugs he will select to reduce the activity of the pyrogenetic processes at work. Amongst the almost numberless antipyretic medicines that have come into use during the last decade, there are but few except autipyriu that have stood the test of time without depreciation of their merits. Antipyrin is one of the most important, the most generally applicable, aud probably the safest antipyretic we possess. A few words regarding its effects iu pyrexial states may be interesting. Shortly after taking it there is slight stimulation, the pulse increases in frequency, and there is often a slight flushing of the face, occasionally followed by pallor. Till
a
against
Succeeding this, perspiration breaks out, varyThe pulse now becomes iu profuseuess. slower (but not altogether in ratio to the reduction of the temperature), and the tem-
ing
perature is lowered
to au extent
that 38
closely
*
294
INDIAN MEDICAL GAZETTE.
with the amount of the drug adIn some cases we have seen the temperature reduced below the normal. Associated with the fall of temperature is a general improvement of the patient, cessation of restlessness, and delirium, cleaning of tongue, where these signs and symptoms are present. In the more continuous forms of fever, however, this lowering of the temperature is not permanent, but in from two to six hours it begins to rise again. This rise is frequently ushered in by a chill where no such symptom was present in the previous exacerbation, that is, before the drug was given. In this connection its action is solely confined to the reduction of temperature. It has practically no effect whatever on the course of long-continued, especially, specific fevers. That it likewise reduces the normal temperature. Of this I have repeated personal proof whenever three 10-grain doses have been taken for trigeminal neuralgia. I have likewise noticed the same effect upon The temperature lowers about 1? F. others. With regard to the manner in which it reduces the temperature, Cappola quoted by *' Ringer, concludes that antipyrin lowers the body temperature by increasing radiation, and not by lessening the production of heat, for it increases the strength of the heart's contractions, and does not lower blood-pressure. The vascular dilatation does not depend on depression of the vaso-motor centre, but is peripheral, and it occurs in tissues separated from the central nervous system." It would be out of place here to introduce the question as to the somewhat complicated and elaborate speculations that have been made with regard to the essential causes of abnormal thermogenesis. Still we cannot consider that Cappola's explanation as to the action of antipyrin in reducing temperature is complete. The fact that many other drugs which increase radiation and effect dilatation of the arterioles such as pilocarpin, chloral hydrate, nitrate of amyl, &c., are not such valuable antipyretics, points to this conclusion. If we adopt the theory of some excellent authorities, antipyrin, in addition to increasing radiation of heat, antagonises the abnormal thermogenesis, by acting as a sedative to the heat generating centres. Those who oppose the use of antipyrin in pyrexial states do so chiefly on the grounds that its action is only temporary, and associated with depression. With regard to the repeated large-dose method of using it, I have no doubt but that such a contention would be justifiable. My experience and conclusions are mainly directed by supporting the frequently repeated small-dose plan of administering the drug. By it the temperature is certainly lowered more gradually, but when reduced, I believe (although I have not sufficient evidence at present to
corresponds
ministered.
*
[Oct.
1891.
the period of remission is longer. results equally efficacious to those appertaining to the large-dose system, and certainly less dangerous. Should any untoward results arise, the drug may be promptly stopped. We thus adequately secure its antipyretic action without enlisting its depressant properties, and this we may affirm notwithstanding Ringer's statement to the effect that " a single 30 grain dose appears to depress less than smaller doses more frequently repeated," and that "antipyrin like other antipyretics, causes so much distress and depression that in many cases it does more harm than good, though I think it is less depressing than other antipyretics." But elsewhere he remarks that it is " a safe and sure reducer of febrile temperature." It is quite conceivable that, in the case of all drugs, the use of which will effect the reduction of the temperature, say from 106? F. to 98? F. within a few hours, such a result will be followed by
prove These
this), are
-
depression. With regard to other antipyretics, such as kairin, thallin, chinoliu, phenacetin, &c., statements Hke the following are sufficient to put
end to one's use of them. " The actions of kairin, &c., have not proved satisfactory, and so much depression has been caused by them to be dangerous. The more recent and as remedies have now.displaced them manageable
an
entirely." (Barthelow.) Experiments on animals have proved antipyrin strengthens the contraction of
that both the auricles and ventricles. In this way it differs very much from its congeners kairin and thallin paralysing the ventricles; hydrochinon aud resorcin weaken the ventricles less, but greatly weaken the auricles and lower the tone of the vessels, causing depression by allowing of the accumulation of the blood in the veins, the animal depleting itself into its own veins. Nevertheless, it is a safe rule never to give it to patients suffering from the depressing effects of
prolonged pyrexia, except
as
a
desperate
mea-
We have always looked upon a weak first sound as a coutra-iudication to the use of the drug. Taking warning from the history of tiie many fatal cases reported from the use of antipyrin, we very rarely prescribe it, when there is any manifest cardiac weakness present. If in such an instance, the gravity and peculiar nature of the case leads to the use of antipyrin sure.
as an
it
exceptional
by stimulants. Antipyrin has
measure, we
invariably guard
an extensive field of usefulness in malarial fevers, especially those of the remittent type. Here the small-dose method systematically adopted, and combined with ordinary diaphoretics during each day's exacerbation will keep the pyrexia within bounds, will reduce tiie headache and pains in the bones as well as relieve to some extent the feelings of general
Oct.
discomfort, the
HEHIR ON ANTIPYRIN.
1891.] but it has
110
influence in
the remedies preventing replace familiar.
ensuing accession of temperature; it is
not
At the same in its properties. curious fact that the actively moving bannato-monads contained in the blood of malaI'ial patients, are rendered motionless by contact This with a 1 to 100 solution of antipyrin. was proved by irrigating the field of a prepared specimen and watching the effects microsdry immersion. This is copically with a readily understood if we remember that antipyIn ague it lias rin is a protoplasmic poison. similar effects. It lessens the length of the hot stage by from half to one-and-a-half hours. This we have proved by daily observation of patients admitted into the Staff Hospital. It produces a proneness to chill from free perspiration, sometimes tends to cause an apparent It occurred in second attack 011 the same day. the case of a sepoy now under treatment in the Staff Such an event, however, is
antiperiodic time it is
rare.
a
Hospital".
In enteric fever, the collected experience of various authors and published papers in medical journals warrants the assertion that it is the most trustworthy and safest antipyretic that can be used in this disease. BrigadeSu rgeon Hamilton, although he prefers the use of antifebrin to that of antipyrin, with regard to the latter remarks: "So long as the patient is in a fairly sthenic condition, I have never seen any ill-effects follow its use (in enteric fever*)". He gives it in 20-grain doses, combining its use with brandy after the first dose. Dr. Lauder Brunton states that it " seems especially useful in typhoid fever." The late Deputy Surgeon-General D. B. Smith, M.D., F.r.c.p., held a high opinion of antipyrin in this disease. " The published experience in the great journals of professional opinion, in respect to the utility of autipyriu in typhoid fever, now constitutes a vast literature in itself. That autipyriu is a safe and efficient antipyretic in typhoid is generally admitted. In the condition of hyperpyrexia its timely administration has
proved very beneficial." It has lately been advocated
as an efficient in the treatment of acute rheumatism. It is said to arrest the pains and discomfort, and to lower the temperature. There is, however, but limited support for the position assumed for antipyrin in comparison with salicylic acid and its soda salts, the latter being much superior.
IIEHIR,
m.d., f.r.c.s.e.
Antipyrin,
known to pharmocologists by overwhelming and impracticable name of Dimethyloxyquinizine, is the term originally
the
the proprietors and discoverers to one of the most popular antithermic remedies that have been introduced into our pharmacopoeia within recent years. It is an alkaloid, synthetically prepared from chinolin, Although the name given to this drug expresses the most significant of its therapeutic properties, it is now a well-known fact that to limit its employment to the reduction of febrile temperature would be considerably curtailing its sphere of usefulness. Whilst we cannot be too lavish in our praises of those excellent workers by whose indefatigable efforts our defensive agents against disease are being constantly enriched, we cannot lose sight of the fact that it frequently happens that in the original announcement of the discovery and description of a new drug, the enthusiasm of the discoverer often leads him to over-estimate the therapeutic properties of the new-born remedy, and thereby tends to cast discredit on those virtues which the drug actually possesses, or the drug rapidly rises in popularity on account of the eulogistic terms in which it is represented to the profession. So it was with antipyrin, early after its discovery by Knorr, and the first inquiry as to its uses in clinical medicine by Filchne (who rather under-rated or at least limited its therapeutic value), the number of investigations rapidly increased, and within a few years the published literature on the subject of its therapeutic applicability became enormous. It was considered by some to be a sort of panacea, a universal specific. But happily for the profession we have other diligent labourers constantly engaged in rectifying such discrepancies as these, men whom experience has taught to sift the wheat from the chaff, and who soon advise us as to the special benefits to be derived from all newly discovered remedies,and cautiou us where care and discretion are demanded. But antipyrin is not accepted by all as an unalloyed boon. From many quarters one finds attempts made to depreciate its use, and I am convinced that amongst certain physicians at least, and these men of high standing in the profession, there is at the present day a prejudice against the use of all the more receutly discovered antipyretics, especially those of the
given by
0
?
t
Oct.
1891.]
HEHIR ON ANTIPYRIN.
coal-tar derivatives, claiming that the depressant action of such drugs in the febrile state is
for alarm than the condition they intended to antagonise. But in the case of antipyrin this is an extreme view, and holds good only with regard to what might be considered poisonous doses. There is now overwhelming evidence to the effect that the practitioner who entirely sets his face against the use of antipyrin robs himself of one of his most powerful auxiliaries in many cases, and he does so to the detriment of his patients. In antipyrin we, doubtless, have a potent agency, but there is no more reason that we should use it without care and discretion than that we should use morphine in toxic doses where smaller ones will effect the desired end. It has surely never been conceived that because a one-grain dose of morphine or strychnine frequently repeated would quickly prove fatal, therefore lesser doses are not to be used in any case. If it be contended that the smaller doses of antipyrin frequently repeated do not act so efficiently as the larger doses given at longer intervals, I, with all due deference, express a contrary view, and have many high authorities to support me in this opinion. Notwithstanding the volumes of adverse criticism to which this drug has been subjected it has gained ground, and as far as its use in the treatment of certain diseases and symptoms are concerned, its position has been established. The differences of opinion expressed by different authorities regarding the drug are in a measure explained by the difference in the quantity administered at each dose, or over a given time. In a number of standard works, "we find doses of 20, 30, and even 60 grains advocated, the dose differing, of course, in accordance with the reason for which it is administered. The dose advised in pyrexia! states by Lauder Brunton is 30 grains repeated three times, by Ringer 20 to 60 grains, by Barthelow 10 to 60 grains, and by Waring 20 to 30 grains every hour, for four doses. The use of such large doses as an orthodox practice would, I think, in India be fraught with the utmost danWe are acquainted with one case, at least, ger. in which an aggregate of 80 grains taken in three hours proved fatal. Personally I am convinced that in this climate as a rule the maximum dose of 10 to 15 grains should not be exceeded, and that even this quantity should not be frequently repeated except under extreme circumstances, e. g., when the antipyretic action of the drug is demanded without delay. I usually give it in hourly doses of 10 grains repeiited for 5 or 6 doses according to the effect required, or half hourly doses of 5 grains to reach the same quantity. In children, when necessary, f of a grain for every year of age is prescribed hourly. I have prescribed it successfully in more a cause are
293
accordance with this method in pyrexial states in in all ages, even in the case of a new-born infant; and I have never witnessed any of the serious effects described by some authorities, although we sometimes have been obliged to discontinue its use, especially in the case of children. In prescribing it for these latter, it is necessary to watch the effects carefully. It is a very convenient remedy, and has some general advantages appertaining to its use, amongst which are, its ready solubility iu water; it is not unpleasant to the taste, rarely irritates the stomach, and it rapidly diffuses into the blood. It occasionally produces an eruption like that of measles, which appears on the trunk chiefly, but never on the face. We have frequently seen it produce a passing erythematous blush. On two occasions it produced a large vesiculo-pustular eruption, and on one an urticarial rash without the irritation, however, of ordinary urticaria. It is said that large It doses sometimes cause hasmoglobinuria. may be given in various ways?in solution, in tabloids, cachets, wafer enclosed in paper,
hypodermically,
or
as a
deep-seated injection.
These latter we have found to give some pain as a rule, which might be relieved either by combining the solution with ? grain morphiue For hypoor a similar quantity of cocaine. dermic use 10 grains are dissolved in 10 minims of hot water, and allowed to cool before using. We may now pass on to consider its use iu certain diseases and symptoms beginning with those in which the drug is employed tor its
antipyretic properties.
few years ago our therapeutic resources the more severe forms of pyrexia were limited to quinine, salacin, aud its salts, and cold water, but at the present day we suffer from an embarras de richesses in relation to antipyretic remedies, the physician, if he is disposed to use such agents being sometimes puzzled as to which of the many fever-reducing drugs he will select to reduce the activity of the pyrogenetic processes at work. Amongst the almost numberless antipyretic medicines that have come into use during the last decade, there are but few except autipyriu that have stood the test of time without depreciation of their merits. Antipyrin is one of the most important, the most generally applicable, aud probably the safest antipyretic we possess. A few words regarding its effects iu pyrexial states may be interesting. Shortly after taking it there is slight stimulation, the pulse increases in frequency, and there is often a slight flushing of the face, occasionally followed by pallor. Till
a
against
Succeeding this, perspiration breaks out, varyThe pulse now becomes iu profuseuess. slower (but not altogether in ratio to the reduction of the temperature), and the tem-
ing
perature is lowered
to au extent
that 38
closely
*
294
INDIAN MEDICAL GAZETTE.
with the amount of the drug adIn some cases we have seen the temperature reduced below the normal. Associated with the fall of temperature is a general improvement of the patient, cessation of restlessness, and delirium, cleaning of tongue, where these signs and symptoms are present. In the more continuous forms of fever, however, this lowering of the temperature is not permanent, but in from two to six hours it begins to rise again. This rise is frequently ushered in by a chill where no such symptom was present in the previous exacerbation, that is, before the drug was given. In this connection its action is solely confined to the reduction of temperature. It has practically no effect whatever on the course of long-continued, especially, specific fevers. That it likewise reduces the normal temperature. Of this I have repeated personal proof whenever three 10-grain doses have been taken for trigeminal neuralgia. I have likewise noticed the same effect upon The temperature lowers about 1? F. others. With regard to the manner in which it reduces the temperature, Cappola quoted by *' Ringer, concludes that antipyrin lowers the body temperature by increasing radiation, and not by lessening the production of heat, for it increases the strength of the heart's contractions, and does not lower blood-pressure. The vascular dilatation does not depend on depression of the vaso-motor centre, but is peripheral, and it occurs in tissues separated from the central nervous system." It would be out of place here to introduce the question as to the somewhat complicated and elaborate speculations that have been made with regard to the essential causes of abnormal thermogenesis. Still we cannot consider that Cappola's explanation as to the action of antipyrin in reducing temperature is complete. The fact that many other drugs which increase radiation and effect dilatation of the arterioles such as pilocarpin, chloral hydrate, nitrate of amyl, &c., are not such valuable antipyretics, points to this conclusion. If we adopt the theory of some excellent authorities, antipyrin, in addition to increasing radiation of heat, antagonises the abnormal thermogenesis, by acting as a sedative to the heat generating centres. Those who oppose the use of antipyrin in pyrexial states do so chiefly on the grounds that its action is only temporary, and associated with depression. With regard to the repeated large-dose method of using it, I have no doubt but that such a contention would be justifiable. My experience and conclusions are mainly directed by supporting the frequently repeated small-dose plan of administering the drug. By it the temperature is certainly lowered more gradually, but when reduced, I believe (although I have not sufficient evidence at present to
corresponds
ministered.
*
[Oct.
1891.
the period of remission is longer. results equally efficacious to those appertaining to the large-dose system, and certainly less dangerous. Should any untoward results arise, the drug may be promptly stopped. We thus adequately secure its antipyretic action without enlisting its depressant properties, and this we may affirm notwithstanding Ringer's statement to the effect that " a single 30 grain dose appears to depress less than smaller doses more frequently repeated," and that "antipyrin like other antipyretics, causes so much distress and depression that in many cases it does more harm than good, though I think it is less depressing than other antipyretics." But elsewhere he remarks that it is " a safe and sure reducer of febrile temperature." It is quite conceivable that, in the case of all drugs, the use of which will effect the reduction of the temperature, say from 106? F. to 98? F. within a few hours, such a result will be followed by
prove These
this), are
-
depression. With regard to other antipyretics, such as kairin, thallin, chinoliu, phenacetin, &c., statements Hke the following are sufficient to put
end to one's use of them. " The actions of kairin, &c., have not proved satisfactory, and so much depression has been caused by them to be dangerous. The more recent and as remedies have now.displaced them manageable
an
entirely." (Barthelow.) Experiments on animals have proved antipyrin strengthens the contraction of
that both the auricles and ventricles. In this way it differs very much from its congeners kairin and thallin paralysing the ventricles; hydrochinon aud resorcin weaken the ventricles less, but greatly weaken the auricles and lower the tone of the vessels, causing depression by allowing of the accumulation of the blood in the veins, the animal depleting itself into its own veins. Nevertheless, it is a safe rule never to give it to patients suffering from the depressing effects of
prolonged pyrexia, except
as
a
desperate
mea-
We have always looked upon a weak first sound as a coutra-iudication to the use of the drug. Taking warning from the history of tiie many fatal cases reported from the use of antipyrin, we very rarely prescribe it, when there is any manifest cardiac weakness present. If in such an instance, the gravity and peculiar nature of the case leads to the use of antipyrin sure.
as an
it
exceptional
by stimulants. Antipyrin has
measure, we
invariably guard
an extensive field of usefulness in malarial fevers, especially those of the remittent type. Here the small-dose method systematically adopted, and combined with ordinary diaphoretics during each day's exacerbation will keep the pyrexia within bounds, will reduce tiie headache and pains in the bones as well as relieve to some extent the feelings of general
Oct.
discomfort, the
HEHIR ON ANTIPYRIN.
1891.] but it has
110
influence in
the remedies preventing replace familiar.
ensuing accession of temperature; it is
not
At the same in its properties. curious fact that the actively moving bannato-monads contained in the blood of malaI'ial patients, are rendered motionless by contact This with a 1 to 100 solution of antipyrin. was proved by irrigating the field of a prepared specimen and watching the effects microsdry immersion. This is copically with a readily understood if we remember that antipyIn ague it lias rin is a protoplasmic poison. similar effects. It lessens the length of the hot stage by from half to one-and-a-half hours. This we have proved by daily observation of patients admitted into the Staff Hospital. It produces a proneness to chill from free perspiration, sometimes tends to cause an apparent It occurred in second attack 011 the same day. the case of a sepoy now under treatment in the Staff Such an event, however, is
antiperiodic time it is
rare.
a
Hospital".
In enteric fever, the collected experience of various authors and published papers in medical journals warrants the assertion that it is the most trustworthy and safest antipyretic that can be used in this disease. BrigadeSu rgeon Hamilton, although he prefers the use of antifebrin to that of antipyrin, with regard to the latter remarks: "So long as the patient is in a fairly sthenic condition, I have never seen any ill-effects follow its use (in enteric fever*)". He gives it in 20-grain doses, combining its use with brandy after the first dose. Dr. Lauder Brunton states that it " seems especially useful in typhoid fever." The late Deputy Surgeon-General D. B. Smith, M.D., F.r.c.p., held a high opinion of antipyrin in this disease. " The published experience in the great journals of professional opinion, in respect to the utility of autipyriu in typhoid fever, now constitutes a vast literature in itself. That autipyriu is a safe and efficient antipyretic in typhoid is generally admitted. In the condition of hyperpyrexia its timely administration has
proved very beneficial." It has lately been advocated
as an efficient in the treatment of acute rheumatism. It is said to arrest the pains and discomfort, and to lower the temperature. There is, however, but limited support for the position assumed for antipyrin in comparison with salicylic acid and its soda salts, the latter being much superior.
