Antipyrinum

Volume IV — Appendix

1 II. Poiimings.—i. a. Two years ago 1 made a communication to Sie Academy of Medicine based upon a case occurring in my practice, irfaere most disagreeable effects had followed the administration of A. '. quoted two other unpublished cases that had been related to me, and hree published cases from English and American periodicals. In the > cases the symptoms noted were : Three times swelling of eyelids to luch an extent that eyes were almost closed, and of face so that 'eatures were scarcely recognisable. Once swelling was chiefly located

throat, and threatened asphyxia. Five times there was a rash of • Accidentally misplaced, — Eds.

ANTIPYRINUM.

lenazon (PhenyWimethyl-pyrazoIon"), C^,HuN,0. A product of coaUtar

throueh toluidm.

some kind, generally erythema or urticaria, with troublesome itching. In one case where there was urticaria there was loss of consciouinesi, which was immediately restored by the hypodermic injection of atropii. In two cases buzzing of ears was noticed. In two also diere «ts violent gastric pain, followed by gastro-enteritis lasting six weeks, it being several mos. before patient entirely recovered. Once there w» profound mental disturbance, patient being afraid of becoming insane; and the mental equilibrium did not return entirely for some mos. Hypersecretion, in the shape of running from nose and eyes and excessive perspiration, was noted several times ; and once patient felt as though she was stuffed with ice.

b^ What I wish to point out now is that I find the symptoms put down to the prevailing influenza are in many cases those described in my paper as due to overdoses of antipyrin, particularly swelling of the eyes, urticaria, and watery discharges. The extensive use of the drug In its treatment is well known. In one case which has come to my knowledge I have no doubt of its having caused death. The patient, an elderly lady, had been treating herself. The symptoms had consisted of cough } a dusky eruption on the body, which appeared swollen; profuse perspiration ; troublesome itching and urticaria, chiefly between the fingers j swelling of the eyelids, which were reduced to a mere slit; and fear of impending insanity. Antipyrin had been taken for about 10 d. and persisted in because of the gravity of the symptoms, which, including pains in the limbs and prostration, seemed to point to the necessity of active treatment. Finally a medical man was called in and the drug stopped : but the patient never rallied and died 2 d. kter. ( (Jennings, Lancet^ Jan. ii, 1890.) (

1. Two patients, a boy and a woman, aet. 10 and 67 respectively, sufl^ered from an eruption after the internal administration of A. The eruption consisted of little irregularly rounded pimples Ipng close together, and in some places confluent, so as to form patches of greater or less extent, between which the skin was normal, thus giving a marbled appearance to the surface. After about 5 d. the eruption began to fade, and to assume the character of a brownish pigmentation ; in the old woman there were some faint evidences of desquamation. Traces of the eruption were still visible at the end of 2 weeks. The eruption was thickest over the body and on the extremities ; the extensor were more covered than the flexor surfaces. In the boy there was some cedema of the face, but in neither case was there any eruption on head or neck ; the palms and soles were not spared. There was some itching in the case of the woman, but the boy did not complain of this. The eruption ran its course and disappeared, although the administration of the A. was not interrupted.* {Praet., Feb., 1885.)

2. A woman, xt. 35, was suffering from blood-poisoning simulating typhoid fever. On the 3rd d. of her being in the hospital, temp, being I03'6° (the highest point it had reached), 35 gr. of A. were administered at 3 p.m., followed 3 h. later by half the quantity. At 6 p.m. temp, was 98*4°, patient pale and still, pulse feeble and rapid. She passed a

• Reporter, Dr. Paul Ernst, states that he has obserred three other cases of exactly

similar nature.

^

restless n., had diarrhcsa and vomiting, skin cool and perspiring. Temp, next m. was 98°. She died in collapse at 1 1 p.m. In the last ^ h. of her life temp, rose again to ioo'6''. {Lancet, Feb, 28, 1885.)

1. TuczEK reports the case of a strong healthy boy, set. 4, who had never had convulsions, rickets, or worms. He had been suffering from whooping-cough, and had taken for three weeks, with marked benefit, 18 gr. of A. daily, when he fell into a condition of somnolence, which had been preceded by lassitude and vomiting, and passed next d, into sopor. In this condition he showed grave motor symptoms — paroxysmal epileptic attacks, some of which were complete, with general convulsions following in regular order, others incomplete, with partial unilateral twitching ; contraction of muscles ; chattering of teeth j jactitation; a peculiar type of breathing somewhat resembling that known as " Cheyne-Stokes' " ; cardiac irregularity, and dilatation of pupils. At the same time a macular eruption of scarlet red colour made its appearance, with sub-normal temp, and slow tense pulse. On 3rd d. consciousness returned, the attacks lessened, and from the 4th d. there was no return. The A. was of coune discontinued at the outset of the seizure, {Practitioner^ Ju'Xi 1889.)

2. In an extensive use of A. in the treatment of whooping-cough, LOEWE met with 3 cases where the action was injurious and attended by alarming symptoms. In one child of 14 mos. a state of great excitement set in after the first dose. The attacks were increased and accompanied by vomiting, the child crying continually, and being thought to be dying. Hydropathic treatment relieved the condition. A second infant, 6 mos. old, after the 2nd or 3rd dose showed cyanosis and collapse, which the same treatment removed. To satisfy himself as to the drug being the cause of these symptoms, Loewe administered a dose himself, when they shortly set in again. In a third child, zt. 2, the attacks appeared to be increased by A., so that besides laryngeal spasm and vomiting general convulsions of marked severity followed the use of the drug, {Ibid.)

3. To a man of 50, suffering from sciatica, 5 gr. were prescribed ter die. The first (and only) dose was taken at 11.30 a.m. He instantly experienced a sensation of tingling and burning in his gums^ which rapidly extended to throat and nose, accompanied by sneezing, running from eyes and nostrils, dizziness, complete loss of vision, a feeling as of numberless pins pricking him down each side of the neck, tightness in throat, and dyspnoea. The pin-pricking sensation extended rapidly down the r. chest and abdomen, was particularly severe in r. side of scrotum and r. testicle, and was also felt in legs and feet— severely in r. and slightly in 1. He next experienced a sensation as if contents of thorax and abdomen were being forcibly drawn upwards toward throat, and r. testicle toward abdomen ; so that, he said, he was "drawn in a ruck," and, being no longer able to stand, fell on the floor. He trembled violently all over, and had cramp in his r. arm and hand. His physician arrived 15 m. after he had taken dose, and found him sitting in a chair, declaring that he was unable to remain recumbent. His face was of a dusky red colour j his nose, lips and

:lids were so swollen as to render his features quite unrecognisable ;

he was trembling violently all over, and fingers of r. hand were clenched in the form of a claw. Pulse scarcely perceptible. The symptoms gradually subsided ; and next d., save for slight headache and loss of appetite, he had completely recovered. {Brit. Med, Jaum.^ Juoe 15th, 1889.)

1. A lady, sensitive even to homoeopathic medicines, took lOgr. for headache at 6 p.m. In 5 m. she was seized with tingling burning sensation round upper part of mouth, inside nostrils, and in palatejuit like cayenne pepper ; this was immediately followed by ineffectual desire to sneeze ; thin clear water poured from both nostrils. These symptoms ceased as suddenly as they had begun, and were immediately followed by sensation of dryness and burning in 1. side of throaty with instantaneous swelling there, and for a few moments absolute loss of voice. The aphonia soon gave way to hoarseness, with much coughing and expectoration which seemed to come from back of throat and nose. With these symptoms there was a lump about an inch thick ia 1. cheek, just below level of upper teeth. Head perfiK:t]y clear, but great nervous anxiety ; trembling of limbs and weakness in walking. These symptoms continued till! 10 p.m., when swelling in throat wa$ relieved by sleep and hot drinks ; but hoarseness was unchanged. At 3 a.m., after further sleep, swelling in throat had almost entirely gone, but same burning tingling sensation was felt in vagina, also nervous pains all over body, She now also had two fainting-spells, with sensation of heart stopping ; also throbbing all over body, coldness of hands and feet, and nervous shuddering without chill. After taking a litde brandy and water, she slept again, and at 7 a.m. all symptoms had gone save the hoarseness, with weakness. Lump in mouth pasted away in J h. During the first symptoms, 1. corner of mouth showed a tendency to draw down. During d. hoarseness continued, with faintness ; frequent passage of clear urine, copious, all the time ; tongue white. Had a little delirium during sleep last n., seeing faces. Yesterday she looked at her throat in a mirror, and found it white, with 1. tonsil inflamed and swollen. (Bell, soon removed remaining symptoms, though weakness persisted some d.) (Berridgb, //<«• Phys.^ Feb., 1890, p. 89.)

ni. Experiments on animals.— i , Experiments were made with A. by R. D, Batten, M.D. and E. G. Bokenham, L.S.A. The drugwtl dissolved in a saline solution and injected into the dorsal lymph uc, or peritoneal cavity, and also administered by the stomach.

a. In the frog, a stage ofdulnessand quiet was followed by inabiL'tj to direct its movements — i.e. after hopping it frequently fell on ia back. Later, when laid on its back, it remained quite still in that petition, making no attempt to regain its normal sitting posture. It would respond to slight stimuli, not by effort to escape, but by an apparently purposeless extension of the legs.

b. In guinea-pigs and rats the onset was usually marked by in impairment of voluntary movement and increasing unsteadiness, the animal standing still and swaying from side to side, often at same time shaking violently. This condition would proceed till the animal WS no longer able to maintain its balance and fell on its side.

c. The most marked early symptom, common to all classes of sub* jtcts, was rigidity of certain sets of muscles. In frogs this usually began in the fore limbs^ and extended to the muscles of the back or ibdomen ; while in the guinea-pig the hind limbs would become suditn\y extended and rigid, so that the animal, on attempting to walk, did JO only with its fore limbs. The rigidity afterwards extended to (he other limbs, the head being drawn back into extreme extension. This rigidity was followed in mammals by peculiar rhythmic move, ments, the limbs moving very rapidly backwards and forwards, as if the animal were running (although it was on its side). If the use of the fore legs were regained, it performed circus movements by their means, alwavt in same direction, round the hinder legs as a centre. The rbycbmic movements alternated with rigidity. Still later the rigidity was less, and extreme irritability came on, a slight tap causing spasm. In severe cases a draught of air or vibration of walking in the room would produce a scries of general convulsions. These symptoms appeared both before and behind a lesion dividing the spinal cord, whence it was concluded that the convulsions (in the frog) are of spinal origin. The rigidity and irritability were entirely abolished, ^ra tem.y by administration of an anaesthetic. Respiration was slowed, shallow, vregular, and with frequent stoppages until death finally ensued. At times the rhythm was that of Cheyne-Stokes* breathing.

d. Summary. — Antipyrin appears to act chiefly on spinal cord, and to a less extent on brain and motor nerves. Analogy leads to the inference that the lateral columns are affected, shown by spastic rigidity 01 using limbs, excessive myotatic irritability, and in one experiment pbenomena exactly resembling ankie-donus. Response to slight stimuli much more marked (viz. in excess) than that to painful stimuli (which *« lessened). {Brit. Med. Joum.y 1889, i, 1222.)

Volume IV — Supplement

ANTIPYRINUM.

(Sec vol. i», p. 487.)

II. 8. In a case of articular rheumatism in which salicylate of soda was not well borne, Brandenberg prescribed i grm. of A. In 5 m. a general toothache set in, together with headache ; pain behind both ears of a tearing character. Symptoms gradually decreased, but toothache lasted 4 h. Patient then took \ grm,, when all the above symptoms returned. {Ailg. h. Zti't.y 1889, No. I2.)