Phenazon (Phenyl – dimethyl – pyrazolon), C11H12N2O. A product of coal – tar through toluidine.
1 a. Two years ago I made a communication to the Academy of Medicine based upon a case occurring in my practice, where most disagreeable effects had followed the administration of A. I quoted two other unpublished cases that had been related to me, and three published cases from English and American periodicals. In the 6 cases the symptoms noted from English and American periodicals. In other 6 cases the symptoms noted were: Three times swelling of eyelids to such an extent that eyes were almost closed, and of face so that features were scarcely recognisable. Once swelling was chiefly located in throat, and threatened asphyxia. Five times there was a rash of some kind, generally erythema or urticaria, with troublesome itching. In one case where there was urticaria there was loss of consciousness, which was immediately restored by the hypodermic injection of atropia. In two cases buzzing of ears was noticed. In two also there was violent gastric pain, followed by gastro – enteritis lasting six weeks, it being several more. before patient entirely recovered. Once there was profound mental disturbance, patient being afraid of becoming insane; and the mental equilibrium did not return entirely for some one. 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.
1 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 f 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; swelling of the eyelids, which were reduced to a mere slit; and fear of impending insanity. Antipyrin had been taken for about 10 day 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 day later. (JENNINGS, Lancet, Jan. 11, 1890.)
2. Two patients, a boy and a woman, aet. 10 and 67 respectively, suffered from an eruption after the internal administration of A. The eruption consisted of little irregularly rounded pimples lying 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 day 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 in the extremities; the extensor were more covered than the flexor surfaces. In the boy there was some oedema 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. (Pract., Feb., 1885.)
3. A woman, aet. 35, was suffering from blood – poisoning simulating typhoid fever. On the 3rd day of her being in the hospital, temp. being 103.6 (the highest point it had reached), 35 gr. of A. were administered at 3 p. m., followed 3 hours later by half the quantity. At 6 p. m. temp. was 98.4, patient pale and still, pulse feeble and rapid. she passed a restless n., had diarrhoea and vomiting, skin cool and perspiring. Temp. next m. was 98. she died in collapse at 11 p. m. In the last 1/2 hours of her life temp. rose again to 100.6. (Lancet, Feb. 28, 1885.)
4. TUCZEK reports the case of a strong healthy boy, aet. 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 day 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; 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 day. there was no return. The A. was of course discontinued at the outset of the seizure. ( Practitioner, July, 1889.)
5. 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, aet. 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.)
6. Two 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 right chest and abdomen, was particularly severe in right side of scrotum and r testicle, and was also felt in legs and feet – severely in right and slightly in I. 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 runk,” and, being no longer able to stand, fell on the floor. He trembled violently all over, and had cramp in his right 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; his nose, lips and eyelids were so swollen as to render his features quite unrecognizable; he was trembling violently all over, and fingers of right hand were clenched in the form of a claw. Pulse scarcely perceptible. The symptoms gradually subsided; and next day, save for slight headache and loss of appetite, he had completely recovered. (Brit. Medorrhinum Journ., June 15th, 1889.)
7. A lady, sensitive even to homoeopathic medicines, took 10 gr. for headache at 6 p. m. In 5m.. she was seized with tingling burning sensation round upper part of mouth, inside nostrils, and in palate, just like cayenne pepper; this was immediately followed by inefficient 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 left side of throat, with instantaneous swelling there, and for a few movements 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 in left cheek, just below level of upper teeth. Head perfectly clear but great nervous anxiety; trembling of limbs and weakness in walking. These symptoms continued till 10 p;. m., when swelling in throat was 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 ringing 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 little brandy and water, she slept again, and at 7 a. m. all symptoms had gone save the hoarseness, with weakness. Lump in mouth passed away in 1/2 h. During the first symptoms, Il corner of mouth showed a tendency to draw down. During day hoarseness continued, with faintness; frequent passage f clear urine, copious, all the time; tongue white. Had a little delirium during sleep last n., seeing face. Yesterday she looked at her throat in a mirror, and found it white, with left tonsil inflamed and swollen. (Belladonna soon removed remaining symptoms, though weakness persisted some days.). (BERRIDGE, Hom. Phys., Feb., 1890, p.89.).
Experiments on animals
1. Experiments were made with A. by R. D.Batten, M. D. and E. G.Bokenham, LSLAL The drug was dissolved in a saline solution and injected into the dorsal lymph sac., or peritoneal cavity, and also administered by the stomach. 1 a. In the frog, a stage of dulness and quiet was followed by inability to direct its movement – left evening, after hopping it frequently fell on its back. Later, when laid on its back, it remained quite still in that position, 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. 1 b. In guinea – pigs and rats the onset was usually marked by an 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 was no longer able to maintain its balance and fell on its side. 1 c. The most marked early symptom, common to all classes of subjects, was rigidity of certain sets of muscles. In frogs this usually began in th fore limbs, and extended to the muscles of the back of abdomen; while in the guineas – pig the hind limbs would become suddenly extended and rigid, so that the animal, on attempting to walk, did so only with its fore limbs. the rigidity afterwards extended to the other limbs, the head being drawn back into extreme extension. this rigidity was followed in mammals by peculiar rhythmic movements, 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, always in same direction, round the hinder legs as a centre. The thymic 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 series 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, protem., by administration of an anaesthetic. Respiration was slowed, shallow, irregular, and with frequent stoppages until death finally ensued. At times the rhythm was that of cheyne – Stokes breathing. 1 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 on using limbs, excessive myotactic irritability, and in one experiment phenomena exactly resembling ankle – -clonus. Response to slight stimuli much more marked (viz., in excess) than that to painful stimuli (which was lessened). (Brit. Medorrhinum Journ. 889, i, 1222.)
APIS (see vol. i, p. 310, 748; vol 2, p.725)
I. 14. A medical man took for an irritation of the throat 13 minims of Apis 0 in water, supposing it to be lachesis 6. He was then galvanising a patient. In about 3 m. he felt a violent blow in the occipital region, and began to feel very strange; the sensation so increased that he had to stop what he was doing. He then sat down and noted his symptoms as they arose, as follows: – Swimming sensation; sense of constriction in throat; twitching of muscles and slight trembling; general sensation of fulness and weakness of co – ordinating power, especially in hands; oppression at bottom of sternum; pain down l. ulnar nerve; weight and tension at back of neck; dimness of sight; sense of weakness in upper limbs; slight numbness of l. hand, particularly of ulnar fingers. (This subsequently increased very much, and amounted to complete anaesthesia of l. ulnar fingers, also want of power, with incomplete anaesthesia of both hands.) The sensation for which he took the dose (“pain as though an oat – husk had stuck in the hyoid fossa”) suddenly disappeared soon after its ingestion, and an habitual irritability of the bladder was diminished. (Monthly Hom. Rev., xxxii, 451.)
II. 19. In 1877 I was stung by a wasp on the r. cheek. Next day, about 4 a. m., I was suddenly awoke by a burning and stinging sensation in my cheek, and a great soreness and smarting along the course of the lymphatics down into my neck. I found my cheek much swollen and red, and there was a patch of redness about the size of a florin that felt as though it were being pierced with red – hot needles. The temporo – maxillary joint was stiff and painful, and a feeling of soreness ran along the gums to the tonsil on that side of my face. After bathing the affected parts for awhile, I got into bed again, feeling somewhat relieved, and fell asleep; but about 2 hours afterwards I was again suddenly roused, this time by a sense of suffocation and difficulty of swallowing, and a renewal of the former distress with intensified severity. Feeling alarmed, I obtained some hot water, to which I added a few dr. of ledum 0, and fomented the whole of the affected region until the severity of the symptoms abated. During the remainder of that day, and for 4 d. afterwards, the attacks continued to recur in paroxysms of more or less severity. The submaxillary and cervical glands on that side of my face became increasingly swollen and tender until the 4th d., when these conditions began gradually to abate, but in the immediate locality of the wound the pains assumed a more constant character, throbbing, smarting, and burning, with periodical stinging and lancinating, and lasting thus for more than a month, though the wound suppurated and discharged freely. The constitutional disturbance consisted of slight rigors and febrile movements, felt mostly in evening (ROWBOTHAM, The Organon, ii, 79.) 20. Mrs. A., Aet. 40, not pregnant, for abdominal enlargement and cessation of menses took 15 dr. of tinct., and repeated dose every 3 h. The next m. her second r. finger began to swell (except the tip), the middle joint especially; it was red and hot; there were burning – stinging pains, with tingling extending up arm to body and down r. side and leg to foot; pains were worse from sundown (5 p. m.) to 6 – 8 a. m., preventing sleep; they were relieved by hot applications and gentle rubbing, or by pinching end of finger, but aggravated by cold applications Apis in high dilution aggravated; improvement under ledum. (TINKER, in Allen’s Encyclopaedia, x, 307.) 21. Mrs. H. was stung by a bee on l. forefinger. She immediately put her finger to her mouth to relieve pain by suction; but in a few moments felt a prickling sensation in lips and tongue. This sensation extended rapidly over face, temples, and head, and thence over entire body, – the sensation now resembling the pain in the finger from the sting. A few m. after the accident there was so much tumefaction of face that the eyes were nearly closed, and the lips and tongue were so much swollen as to interfere with speech. There was distressing sensation of fulness in head, patient declaring that her temples would hurt. She complained of oppression at chest, and inability to take a full inspiration. Skin was intensely red, and covered with an eruption over entire body except the feet, resembling urticaria, causing distressing itching and prickling. There had been severe rig. Pulse was 87 and full. The most prominent symptoms were promptly removed by an emetic, and convalescence ensued in a few day (SPALSBURY, Bost. Medorrhinum and Surg. Journ., liii, 285.)
22. Mr. Walker, a bee – keeper, sought to render himself proof against bee – stings, allowing himself to be well stung on the wrist. The whole forearm was affected with a cutaneous erysipelas, and there was disorder to the nerves, accompanied with heat, redness, swelling, and pain. The day after this attack was over he allowed himself to be stung 3 times more on same spot. The attack which followed was less severe, but, as before, he felt a stinging sensation as far up as the shoulder, and he noticed that a lymphatic gland behind his ear had increased considerably in size. By repeating experiment inflammation grew less and less each time, and at last he could undergo stinging with almost complete impunity. (Lancet, 1874, ii, 883.)
APOCYNUM CANNABINUM (see vol.1, p.
Experiments on animals
1. some experiments on animals have recently been made to ascertain the physiological action of A. by Dr. J. Rose Bradford, who has most kindly allowed me to quote some of the results he has obtained therefrom. In two of these experiments he used a tincture of the root, one in ten of proof spirit. Dr. Bradford finds that the principal action of A. is on the heart. By it the heart of a dog is slowed down to a very remarkable degree, for, when it is well under the influence of the drug, it beats as slowly as two beats to each respiration, or even three beats to every two respirations. This is a much more powerful effect than can be produced experimentally with digitalis; for before this amount of slowing is reached by the latter drug the vagus becomes paralysed, and the heart beats more rapidly and irregularly. A. strengthens the heart’s beat and increases the tonus, so that it stops the frog’s heart in systole. It generally stops the mammalian heart in diastole, but a sudden massive dose may stop the mammalian heart in systole. From this it is evident that the action of apocynum on the heart is similar to that of digitalis, strophanthus, adonidin. caffeine and sparteine, only its power of slowing the heart seems to be greater than in the other members of this group. Its action on the arteries, as shown by changes in the blood – pressure, differs from that of digitalis, for Dr. Bradford finds that apocynum causes no definite rise of blood – pressure, indicating that it does not cause contraction of the arteries.
ARGENTUM NITRICUM (see vol 1.
II. 10. On June 23rd a pharmacy boy was brought to the Hospital St. Louis at 1 a. m. in a state which seemed to indicate imminent death. He was completely unconscious, without sensation in any part of his body; upper limbs and muscles of face were agitated by convulsive movements; jaws were strongly clenched, eyes turned up, pupils very much dilated and insensible to light. Evidence showing that he had taken nitrate of silver, Zss of sea – salt was given in Zj of water every 15 m. After 1.1/2 hours there was sensible improvement; pupils were less dilated, convulsions and clenching of jaws had ceased. The saline solution was continued for 5 hours more. Sensibility was now less blunt, and patient had very severe epigastric pains. It was not till midday, 11 hours after admission, that general sensibility of surface returned and patient recovered his speech. At 3 p. m. he fell into profound coma, which state lasted 2 hours; and similar seizures were repeated on 23rd and 25th. It was not till end of latter day that his state became altogether reassuring. Nothing now interrupted his convalescence, and he left on 29th, having only slight epigastric pains. Patient stated that he had swallowed Zviij of the nitrate, suspended in black currant ratify. (Bull. de Therap., xvii, 195.)