... 7% alpha-globulin, 10% globulin, and 30%gamma-globulin. The patient became pro- gressively more disorientated and required paraldehyde for seda- tion.
Nov. 15, 1958
TO-DAY'S DRUGS
BRISH
MEDICAL JOURNAL
1225
To-day's Drugs
Correspondence
With the help of expert contributors we publish below notes oni a selection of drugs in current use.
Because of heavy pressure on our space, correspondents are asked to keep their letters short. Iproniazid Jaundice SIR,-The three articles concerning the toxic effects of iproniazid (" marsilid ") (Journal, November 1, pp. 1067, 1068, and 1070) are valuable. In view of the reports that iproniazid administration is sometimes associated with jaundice, this case report of a patient who received iproniazid 100 mg. daily for five months and died from hepatic coma may be of interest. Miss C. Y., aged 70, attended the department of cardiology,
Dolviran (Farbenfabriken Bayer A.G.; distributors, Levmedic Ltd.).-Each tablet contains acetylsalicylic acid 0.2 g., phenacetin 0.2 g., codeine phosphate 0.01: g., caffeine 0.05 g., phenobarbitone 0.025 g. The valuable analgesic effects of combinations of aspirin, phenacetin, and codeine are well known. Caffeine is a stimulant of the central nervous system and phenobarbitone is a depressant of the central nervous system. It would seem to be illogical to prescribe them together. The quantity of caffeine in this preparation, however, would have a negligible effect, as it is about a third of what would be contained in a small cup of tea. This preparation is about three times as expensive as compound codeine tablets B.P. N.H.S. basic price: 10 tabs., 2s. 2d. Robaxin (A. H. Robins Co. Ltd.)-This is 2-hydroxy-3o-methoxyphenoxypropyl carbamate (methocarbamol), and is one of the derivatives of mephenesin whicb have been tested in an attempt to find a more effective drug for the relief of skeletal muscle spasm. It has a more prolonged action than mephenesin and has been reported to be effective in treating acute muscle spasm associated with injuries and orthopaedic conditions, but is of only limited use in treating spasticity and rigidity caused by lesions of the central nervous system. It often causes slight drowsiness and dizziness, but serious toxic effects have not been reported. It is supplied in tablets of 0.5 g., and the dose suggested by the makers is 4-9 g. daily, depending on the severity of the spasm. N.H.S. basic price: 50 tabs., 21s. 8d.
(Continued from previous page)
Edinburgh Royal Infirmary, as an out-patient on March 11, 1957, because of effort angina of nine months' duration. Although there was no clinical history of myocardial infarction, an electrocardiogram showed old transmural posterior and anteroseptal myocardial infarcts. Glyceryl trinitrate and restriction of her activities were advised. She was next seen one year later on March 13, 1958, at a routine follow-up clinic, when it was noted that her angina was less incapacitating and that she was able to walk half a mile (0.8 km.) without stopping. ln April her family doctor prescribed iproniazid 50 mg. twice daily, with subsequent reduction of the incidence of angina and of her requirement of glyceryl trinitrate from 8 to 1 or 2 tablets of 1/ 130 gr. (0.5 mg.) daily. On August 8, 1958, her sister noticed that her conversation was muddled and that she was slightly confused. She complained of vague ill-health, and two days later visited her family doctor, who noticed that she was slightly jaundiced and discontinued iproniazid. Her confusion continued, and during the night of August 14 she was found wandering in the garden of her house, shouting and disorientated. On the evening of the following day she was admitted as a certified patient to a mental hospital. Jaundice was present and there was tenderness in the right hypochondrium. Her confusion fluctuated until the third day after admission, when she became semicomatose and deeply jaundiced. She was then admitted to the Edinburgh Royal Infirmary under the charge of Dr. Rae Gilchrist on August 18. Jaundice was marked. There was no history of any contact with infective hepatitis or of any venepuncture as a possible source of homologous serum jaundice. There was guarding in the right hypochondrium, but no detectable hepatic enlargement. There was no splenic enlargement or ascites. Temp. 970 F. (36.1' C.), pulse
cinolone was probably on the high side and was apt to produce excessive side-effects. In another group of patients steroid hypertension was not altered by change to triamcinolone. The new drug had been useful to some patients who were excessively wakeful on prednisolone, but its 70, resp. 18, B.P. 110/60, Hb 970%, W.B.C. 5,300, E.S.R. tendency to reduce appetite and cause loss of weight and 6 mm./hr. The urine contained bile and urobilinogen. Serun weakness was a disadvantage. Other speakers reported that bilirubin 6.3 mg.%, alkaline phosphatase 19 K.-A. units, zinc and triamcinolone caused excessive loss of muscle tissue in some thymol turbidity 8 units each. Serum sodium 128 mEq /i., serum patients, giving the clinical appearance of a myopathy. potassium 3.54 mEq/1., serum chlorides 105 mEq/l. Prothrombin activity 36%. Blood urea nitrogen 19 mg.%. Total proExperience of dexamethasone was limited, but it seemed an teins g.%. Electrophoresis of serum proteins showed that 45% effective drug. Caution was needed, since it had been was 5.8 albumin, 8% alpha,-globulin, 7% alpha-globulin, 10% reported that dexamethasone could suppress the adrenal globulin, and 30% gamma-globulin. The patient became procortex in sub-therapeutic doses, a finding so far not gressively more disorientated and required paraldehyde for sedaconfirmed. tion. Incontinence developed after three days. Serial liver Dr. J. F. BUCHAN (London) had treated 38 ambulatory function tests showed little significant change. She was treated patients suffering from rheumatoid arthritis with chloro- with intravenous 5% glucose saline or 50% glucose with added quine sulphate. In a double-blind trial, objective assess- potassium chloride. Her serum potassium and sodium were conment of disease activity and joint involvement at three and trolled at a steady level until the eleventh day, when her serum dropped to 2.76 mEq/l., from 3.34 mEq/l. Despite six months showed chloroquine sulphate to be clearly, but potassium administration of more potassium chloride, her serum level weakly, effective in this disease. Stainable bone-marrow the remained low and was 2.76 mEq/l. when she died in coma on iron had been studied by Drs. A. G. S. HILL and C. L. September 5. GREENBURY (Stoke Mandeville). It proved to be absent or At necropsy, the liver was flabby and slightly smaller scanty in 56%, and excessive in 22%, of 120 patients with normal (1,070 g.). Its capsule was normal and on sectionthan the rheumatoid arthritis, but there was no correlation with cir- parenchyma was soft, diffluent, and brownish yellow. The intraculating haemoglobin. Remissions of disease induced by hepatic bile ducts showed no macroscopic abnormality. The gallsteroids were accompanied by rise of haemoglobin and dis- bladder contained concentrated bile and was normal. The appearance of excess concentration of marrow iron. Dr. common bile duct was patent and healthy. Histological examiJ. J. R. DUTHIE (Edinburgh) had confirmed that large doses nation revealed subacute and extensive necrosis of the liver: the pattern was partly destroyed and large numbers of polyof intravenous iron (up to 5 g.) induced remission in a lobular morphs and round cells were present in the bile ducts and controlled trial in rheumatoid arthritis. As part of the periportal tissue. The heart showed left ventricular hypertrophy remission there was an improvement in the accompanying and the myocardium had marked focal fibrosis with widespread anaemia. Dr. W. R. M. ALEXANDER (Edinburgh) described patchy necrosis. Although the coronary ostia was patent, the experiments in purifying the rheumatoid agglutinating whole coronary arterial tree was markedly involved with atheroma factor.
1226 Nov. 15, 1958
CORRESPONDENCE .~~~~~~
It cannot be said that tjiis patient died from hepatic coma as a result of iproniazid therapy, but no other cause for her jaundice and liver damage was evident.-We are, etc., Rossbnlee Mental Hospital, !idlothian. J. D. W. FISHER. Royal Infinmav, Edinburgb. M. F. OLIVER.
Aspirin and Gastro-intestinal Haemorrhage SJR,-The article by Dr. L. Th. F. L. Stubbe (Journal, November 1, p. 1062) showing the loss of occult blood after administration of aspirin is alarming when related to the vast quantities of aspirin consumed by the general public. These results are supported by the work of Dr. W. H. J. Summerskill and Dr. A. S. Alvarez published the same week in the Lancet (November 1, pp. 920 and 925). Not only will these results make the consideration of all salicylic therapy a necessity, but raise questions outside the direct controI of the medical profession. Prescribing may be controlled, but what of the vast consumption- by public purchase, and the false idea of safety ? Should not control be exercised ? It is realized that aspirin may not be placed on the Poisons List, but manufacturers should at least be mAde to include a warning on their packings. Is there no method of legislation to enforce this ?-I am, etc., JoHN DOBB1NO. GuY's Hospital, London, S.E.1.
SiR,-Having come pretty near death in my -time from a bleeding duodenal ulcer, after taking aspirin for incidental headaches, I do not need to be convinced that aspirin makes ulcers bleed. But Dr. L. Th. F. L. Stubbd, in his most interesting paper (Journal, November 1, p. 1062), shows that taking aspirin regularly for a weel or so will make even a normal volunteer lose more than 4 ml. of blood a day from his intestinal tract in two-thirds of cases. This seems to prove that it is dangerous to take a couple of aspirins three times a day for chronic painful conditions, such as " rheumatism." It looks as if some other analgesic, or coated tablets of sodium salicylate, will have to be tried in such patients. But it would surely be a pity if Dr. Stubb4's admirable bit of work was applied to taking occasional doses of aspirin for headaches, etc. This is about the most effective of our " bathroom cupboard " analgesics and hitherto has seemed as safe as its nearest rival-a double whisky. Even if two or three aspirins do turn out to cause gastric hyperaemia and consequent oozing of blood from the gastric or intestinal mucosa, provided this occurs only once in a while, need one bother much ? Because, as you will recall, the second figure in Douthwaite and Lintott's paper' on the gastroscopic findings after aspirin was an illustration of the effect of a single dose of mustard, as taken with beef steak. And their fine colour photographs demonstrated convincingly that, though chunks of aspirin produced a localized hyperaemia, the mustard produced a more generalized and at least equally intense gastric reaction. Before frightening the public into giving up their favourite home remedy for occasional familiar pains, should we not warn them that their taste for condiments is probably quite as dangerous ? Or can we be reassuring on the present findings, provided, as always, that they practise moderation? -I am, etc., E. CLAYToN-JoNES. Tonbridge. REVEM"CE Douthwaite A. H., and Lintott, G. A. M., Lancet, 1938, 2. 1222.
Antibiotic Therapy for Bronchitis SmR,-l read with interest the article on continuous antibiotic therapy for adult chronic bronchitis by Drs. Gordon Edwards and E. C. Fear (Journal, October 25, p. 1010). This is a very common ailment especially here in the North, and already " this season " I have treated chronic bronchitics for their more acute relapses. I was therefore delighted to see how the treatment as advocated in the article gave such significant relief. But the sting comes at the end -the cost of the tetracyclines was £45-£55.
MEIA
JOURNAX
In these days of very necessary awareness of costs, what am I to do ? If I treat, say, only a few of the many bronchitics in this practice, the costing department of the Ministry of Health will not look upon me with favour. The fact that I am possibly saving expenditure in other Ministries does not interest them, neither does the fact that the patient continues working throughout the winter show in any Ministerial estimates. A hospital bed not used sounds a weak argument to account for above-average prescribing. My moral obligation to the patient is to help his discomfort and improve his prognosis. I would be grateful for guidance in this problem.-I am, etc., Wilmslow, Cheshire.
A. H. LUSCOMBE.
Foreign Body in Endotracheal Tube SIR,-I wish to record a rather unusual case of respiratory obstruction during endotracheal anaesthesia. The patient was anaestheti7ed and intubated with a large u, Portex endotracheal tube. He immediately showed signs of respiratory ob_"s struction. Manual squeezing of the reservoir bag was met by resistance, and produced no expansion of the chest. Laryngoscopy showed no obvious cause of obstruction, so the endotracheal tube was removed with immediate relief, thus confirming the -advice, "Respiratory obstruction can be relieved by the simple expedient of withdrawing the tube and giving the patient a chance to breathe normally."' On examination of the tube the lumen was found to be completely obstructed by a cork., The radiograph shows the cork in situ outlined with barium. A similar cause of obstruction has recently been described.2-1 am, etc., The Royal Infirmary, K. A. SrEWART. Cardiff.
2
REFERENCEs Macintosh, R. R., Mush.n, W. W., and Epstein, H. G., Physics for the Aneestiwst, 2nd edition. p. 269. Blackwell Scientific Publications. Haselhuhn, D. H., Anaestliesology. 1958, 19, 561.
Hydrocortisone for Asthma SIR,-In the Journal of September 27 three papers dealing with the hydrocortisone treatment of bronchial asthma' ' describe methods we introduced sevcral years ago in our department." We administered prednisone powder+lactose by nasal and oral insufflation and hydrocortisone solution by oral spray. The first method we tried on asthmatics with rhinitis and tracheobronchitis, using double-blind control groups of lactose and quinine insumflations. The results were checked by relief of symptoms. The treatment was successful in cases where rhinitis predominated. In hydrocortisone inhalation therapy the presence of blocking mucus in the bronchi and bronchioli presented the greatest problem. We worked out a method of sucking this mucus by a double catheter introduced into the trachea as far as the bifurcation; the suction was achieved by electric apparatus. After this preliminary treatment patients inhaled a solution containing 50-150 turbidity-reducing units of hyaluronidase (" hyason ") and 25 mg. hydrocortisone (" hydroadreson "). The hyaluronidase facilitatesthe absorption of hydrocortisone on the mucous membrane. We continued this treatment twice weekly, giving 3-30 treatments per case, depending on the severity of the asthmatic state. About 300 cases of asthma have been treated in the past four years. We controlled our cases by serial determinations of 17-ketosteroid excretion and vital capacity. We found that removal of mucus, hyaluronidase, or hydrocortisone spray alone caused neither a significant rise of vital capacity nor of 17-ketosteroid secretion, but 3-6 combined treatments had a marked effect. For treatment we selected cases of severe intractable asthma, gaining a good response in 50-60%. Patients with secondary complications (emphysema, cor pulmonale, bronchiectasis) did not respond well, whilst infective agents were eliminated by simultaneous penicillin-streptomycin inhalation.
