Microscopic Colitis: Collagenous Colitis and Lymphocytic Colitis
PENICILLIN-ASSOCIATED COLITIS
1
1151 W.H.O. ESSENTIAL DRUGS SIR,-You have cautiously welcomed the list of about 200 essential drugs published by an expert committee of W.H.O., but point out that some drug companies are less than enthusi- astic about it.’ I think this list is a valuable guide for the sup- ply of drugs not only to poorer countries but for everyone. The number of drugs is not limited to 200 and drugs of equal effi- cacy and quality can supplement the list where necessary, as with antihistamines or beta-blockers. However, one important point has not been mentioned- namely, the fixed combinations. The W.H.O. list contains orily 3 (co-trimoxazole, carbidopa, and ethinylestradiol-containing pills) with 2 topical skin preparations and 1 vitamin mixture. 1 have counted the fixed combinations in M.I.M.S. (a U.K. drug list) in the first two parts of the drugs for the alimentary sys- tem and have found some 62 combined preparations as against 27 single drugs; among the diuretics and antidiuretics there were 15 combined and 32 single preparations, but in the sec- tion on analgesics and antipyretics there were 42 combined drugs and 29 single ones. In West Germany some 8000 fixed combinations are on the market, mostly senseless and ineffi- cient products. In Germany the drug industry is either protest- ing at the classification as non-essential of this profitable, but medically useless, market or it is trying to pretend that the list is meant only for the underdeveloped countries. There are many good reasons against most fixed combina- tions and I know that these were in the mind of the W.H.O. committee when they decided on the almost complete exclusion of drug combinations. The lack of enthusiasm of some drug firms for this list is easy to understand. They ought to be look- ing for new effective remedies instead of combining again and again old ones of often doubtful efficacy. 9 Park Crescent, London N3 H. HERXHEIMER SIR,-Whilst I appreciate the developing countries’ view that they cannot afford modern drugs it would seem that most, if not all, of these countries stand in much greater need of improved sanitation and hygiene: perhaps, in concentrating their minds on medicines, these countries have not got their priorities right. What is the use of administering an effective anthelminthic to a patient who then drinks or bathes in in- fested water? All the same many pharmaceutical companies, including Janssen, have embarked on programmes designed to identify new and improved medications for the severely debili- tating diseases widespread in developing countries. In further- ance of this interest, Janssen Pharmaceutical n.v. are organis- ing an international symposium on Health Policy in Developing Countries, which will take place at Beerse, near Antwerp, on April 20/21, 1979. Complimentary copies of the proceedings will be obtainable from me. ’ Janssen Pharmaceutical Ltd, Marlow, Bucks SL7 1ET R. LEVIN PENICILLIN-ASSOCIATED COLITIS SIR,-Dr Toffler and colleagues (Sept. 30, p. 707) describe five patients with penicillin-associated transient acute colitis. We have seen a similar case. A 31-year-old woman came to our outpatient clinic with low- er-abdominal cramps and bloody diarrhoea. 5 days previously treatment with phenethicillin, 250 mg three times daily by mouth, had been started because of a sore throat. She was tak- ing an oral contraceptive but no other drugs. After the first day of phenethicillin treatment mild abdominal discomfort 1. Lancet, 1978, i, 423; ibid. ii, 977. 2. Herxheimer, H Int. J. clin. Pharmac. Biopharm. 1975, 12, 70. developed: within 3 days this had progressed to voluminous non-bloody diarrhoea, but over the next 2 days the pattern changed to frequent bloody diarrhoea and anal tenesmus. There was no previous history of bloody diarrhoea. Physical ex- amination revealed no abnormalities except a mild abdominal tenderness and subfebrile temperature (37-6°C). ’. An immediate sigmoidoscopy to 15 cm showed blood and yel- lowish-brown mucus passing down the lumen, but no signs of mucosal inflammation or ulceration. Laboratory findings were: erythrocyte-sedimentation rate 12 mm/h; Hb 9.0 mmol/1 (normal); white blood-cells 12-8x10/1 (normal 4-10 x 109) with normal differential; stool cultures twice negative for Shigella, Yersinia, Campylobacter, and Salmonella, with no worms or cysts. Barium enema, 14 days after the onset of the first symptoms, showed no abnor- malities. The patient was not admitted. Phenethicillin had been dis- continued on the day before the first visit, and after 2 days all symptoms disappeared. There has been no recurrence. In this case the acute colitis was not proved by prompt bar- ium enema or by coloscopy. The course of the disease sug- gested that we were dealing with a penicillin-induced acute bloody diarrhoea, probably a proximal colitis; recovery im- mediately followed discontinuation of the drug. The rapid and complete recovery after withdrawal of the penicillin medi- cation, as in the earlier cases, makes the need for prompt bar- ium enema questionable. Department of Internal Medicine, University Hospital, Nijmegen, Netherlands P. DE MULDER TH. THIEN J. F. M. FENNIS ACETYLATOR STATUS AND RESPONSE TO PHENELZINE SIR,-We would like to comment on Dr Tyrer and Dr Gardner’s letter of Nov. 4 (p. 994). We have shown phenelzine to be a substrate for rodent and human hepatic N-acetyltrans- ferase.’ In a study of samples from patients with neurotic depression we found a correlation between urinary excretion of phenelzine and acetylation of sulphadimidine. The correlation was present in the group as a whole (fast and slow acetylators together) and for the range of results within an acetylator phenotype group. 1 Therefore if there is a dose response relationship (as de- scribed by Tyrer and Gardner and others) it is difficult to see why there should not also be a relationship between response and acetylator status. This may not be readily detected since the ease with which the acetylation dependence can be demon- strated will be dependent on the relative importance of acetyla- tion and other routes of elimination, on the accuracy of assess- ment of acetylator status, and on the variability in response to treatment shown by the patients (which is always considerable in the diagnostic groups with which we are concerned). Schroder’s technique of acetylator phenotyping2 is qualita- tive and subject to error. Dr Tyrer arranged for us to check by more accurate means the acetylator phenotype of five of his patients, one of whom gave discordant phenotyping, but speci- mens from the remaining fifty five were not available to us. Our earlier publications show a relationship not only between acetylator status and clinical outcome3 but also, in a separate group of patients, a relationship between monoamine- oxidase inhibition and acetylator phenotype.4 This latter rela- tionship was present after two weeks of treatment but not thereafter since the fast acetylators, unlike the slow acetyla- 1. Tilstone, W. J., Margot, P., Johnstown, E. C. Psychopharmacology (in the press). 2. Schroder, H. Br. med. J. 1972, in, 506. 3. Johnstone, E. C., Marsh, W. Lancet, 1973, i, 567. 4. Johnstone, E. C. Psychopharmacologia, 1976, 46, 289.
Transcript of PENICILLIN-ASSOCIATED COLITIS
1151
W.H.O. ESSENTIAL DRUGS
SIR,-You have cautiously welcomed the list of about 200essential drugs published by an expert committee of W.H.O.,but point out that some drug companies are less than enthusi-astic about it.’ I think this list is a valuable guide for the sup-ply of drugs not only to poorer countries but for everyone. Thenumber of drugs is not limited to 200 and drugs of equal effi-cacy and quality can supplement the list where necessary, aswith antihistamines or beta-blockers.
However, one important point has not been mentioned-namely, the fixed combinations. The W.H.O. list contains orily3 (co-trimoxazole, carbidopa, and ethinylestradiol-containingpills) with 2 topical skin preparations and 1 vitamin mixture. 1have counted the fixed combinations in M.I.M.S. (a U.K. druglist) in the first two parts of the drugs for the alimentary sys-tem and have found some 62 combined preparations as against27 single drugs; among the diuretics and antidiuretics therewere 15 combined and 32 single preparations, but in the sec-tion on analgesics and antipyretics there were 42 combineddrugs and 29 single ones. In West Germany some 8000 fixedcombinations are on the market, mostly senseless and ineffi-cient products. In Germany the drug industry is either protest-ing at the classification as non-essential of this profitable, butmedically useless, market or it is trying to pretend that the listis meant only for the underdeveloped countries.
There are many good reasons against most fixed combina-tions and I know that these were in the mind of the W.H.O.committee when they decided on the almost complete exclusionof drug combinations. The lack of enthusiasm of some drugfirms for this list is easy to understand. They ought to be look-ing for new effective remedies instead of combining again andagain old ones of often doubtful efficacy.9 Park Crescent,London N3 H. HERXHEIMER
SIR,-Whilst I appreciate the developing countries’ viewthat they cannot afford modern drugs it would seem thatmost, if not all, of these countries stand in much greater needof improved sanitation and hygiene: perhaps, in concentratingtheir minds on medicines, these countries have not got theirpriorities right. What is the use of administering an effectiveanthelminthic to a patient who then drinks or bathes in in-fested water? All the same many pharmaceutical companies,including Janssen, have embarked on programmes designed toidentify new and improved medications for the severely debili-tating diseases widespread in developing countries. In further-ance of this interest, Janssen Pharmaceutical n.v. are organis-ing an international symposium on Health Policy in
Developing Countries, which will take place at Beerse, nearAntwerp, on April 20/21, 1979. Complimentary copies of theproceedings will be obtainable from me.
’
Janssen Pharmaceutical Ltd,Marlow, Bucks SL7 1ET R. LEVIN
PENICILLIN-ASSOCIATED COLITIS
SIR,-Dr Toffler and colleagues (Sept. 30, p. 707) describefive patients with penicillin-associated transient acute colitis.We have seen a similar case.A 31-year-old woman came to our outpatient clinic with low-
er-abdominal cramps and bloody diarrhoea. 5 days previouslytreatment with phenethicillin, 250 mg three times daily bymouth, had been started because of a sore throat. She was tak-ing an oral contraceptive but no other drugs. After the firstday of phenethicillin treatment mild abdominal discomfort
1. Lancet, 1978, i, 423; ibid. ii, 977.2. Herxheimer, H Int. J. clin. Pharmac. Biopharm. 1975, 12, 70.
developed: within 3 days this had progressed to voluminousnon-bloody diarrhoea, but over the next 2 days the patternchanged to frequent bloody diarrhoea and anal tenesmus.There was no previous history of bloody diarrhoea. Physical ex-amination revealed no abnormalities except a mild abdominaltenderness and subfebrile temperature (37-6°C). ’.An immediate sigmoidoscopy to 15 cm showed blood and yel-
lowish-brown mucus passing down the lumen, but no signs ofmucosal inflammation or ulceration.
Laboratory findings were: erythrocyte-sedimentation rate12 mm/h; Hb 9.0 mmol/1 (normal); white blood-cells12-8x10/1 (normal 4-10 x 109) with normal differential; stoolcultures twice negative for Shigella, Yersinia, Campylobacter,and Salmonella, with no worms or cysts. Barium enema, 14days after the onset of the first symptoms, showed no abnor-malities.The patient was not admitted. Phenethicillin had been dis-
continued on the day before the first visit, and after 2 days allsymptoms disappeared. There has been no recurrence.
In this case the acute colitis was not proved by prompt bar-ium enema or by coloscopy. The course of the disease sug-gested that we were dealing with a penicillin-induced acutebloody diarrhoea, probably a proximal colitis; recovery im-mediately followed discontinuation of the drug. The rapid andcomplete recovery after withdrawal of the penicillin medi-cation, as in the earlier cases, makes the need for prompt bar-ium enema questionable.
Department of Internal Medicine,University Hospital,Nijmegen, Netherlands
P. DE MULDERTH. THIEN
J. F. M. FENNIS
ACETYLATOR STATUS AND RESPONSE TOPHENELZINE
SIR,-We would like to comment on Dr Tyrer and DrGardner’s letter of Nov. 4 (p. 994). We have shown phenelzineto be a substrate for rodent and human hepatic N-acetyltrans-ferase.’ In a study of samples from patients with neuroticdepression we found a correlation between urinary excretion ofphenelzine and acetylation of sulphadimidine. The correlationwas present in the group as a whole (fast and slow acetylatorstogether) and for the range of results within an acetylatorphenotype group. 1
Therefore if there is a dose response relationship (as de-scribed by Tyrer and Gardner and others) it is difficult to seewhy there should not also be a relationship between responseand acetylator status. This may not be readily detected sincethe ease with which the acetylation dependence can be demon-strated will be dependent on the relative importance of acetyla-tion and other routes of elimination, on the accuracy of assess-ment of acetylator status, and on the variability in response totreatment shown by the patients (which is always considerablein the diagnostic groups with which we are concerned).
Schroder’s technique of acetylator phenotyping2 is qualita-tive and subject to error. Dr Tyrer arranged for us to checkby more accurate means the acetylator phenotype of five of hispatients, one of whom gave discordant phenotyping, but speci-mens from the remaining fifty five were not available to us.Our earlier publications show a relationship not only
between acetylator status and clinical outcome3 but also, in aseparate group of patients, a relationship between monoamine-oxidase inhibition and acetylator phenotype.4 This latter rela-tionship was present after two weeks of treatment but notthereafter since the fast acetylators, unlike the slow acetyla-
1. Tilstone, W. J., Margot, P., Johnstown, E. C. Psychopharmacology (in thepress).
2. Schroder, H. Br. med. J. 1972, in, 506.3. Johnstone, E. C., Marsh, W. Lancet, 1973, i, 567.4. Johnstone, E. C. Psychopharmacologia, 1976, 46, 289.
