1
463 excreted primarily in the urine. Three main substances emerge in the urine-the unchanged drug, its sulphone derivative, and a dihydroxylated derivative. A sulphide metabolite with a long half-life is present in plasma but not urine, probably because of extensive binding to plasma proteins. In several anti-inflammatory assays, the sulphide metabolite has been shown to be as active as indomethacin. Sulindac (’Clinoril’) was the subject of a special sym- posium at the VIII European Rheumatology Congress, Helsinki, Finland, in June, 1975. Eighteen papers read at that symposium have now been published,’ and they deal with the pharmacology of sulindac and the efficacy of this drug versus aspirin, ibuprofen, phenylbutazone, and oxyphenbutazone. In osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, gout, and acute painful shoulder, sulindac seems to be as effective and in many instances better tolerated than the other drugs. Few reports have appeared in the U.K. journals, but one clinical triaP comparing sulindac (400 mg/day) with ibuprofen (1200 mg/day) in osteoarthrosis of the hip showed that the two drugs were much the same in terms of patient and doctor preference, effects on hip move- ments, and toxicity. No serious side-effects were encoun- tered, and the analgesic properties of sulindac were superior to those of ibuprofen. Like all anti-inflammatory drugs, sulindac should be used with caution in patients with a history of gastro- intestinal upset, and since the drug is excreted largely via the kidneys the dosage should be reduced in renal impairment. It is known that steroids, especially those containing fluorine (e.g., triamcinolone), may produce a myopathy, but no muscle cramps or myopathies have occurred during four years of clinical trials with sulin- dac. Side-effects do not seem to be as frequent as with indomethacin, but these are early days. The maximum dose administered to date has been 400 mg/day, but wider clinical experience may well reveal that this dose is insufficient in certain rheumatic conditions. One of the advantages of sulindac is that it need be given only twice-a-day. Each tablet of clinoril contains 100 mg of sulindac and the recommended dosage is 100-200 mg twice-a-day. The rheumatologist or general practitioner in the U.K. can be excused for taking a cau- tious attitude to a new anti-inflammatory agent. With so many non-steroidal anti-inflammatory drugs to choose from, and many of the patients taking more’than one preparation, it will be a long time before we know the true worth of sulindac. Existing evidence suggests that it is effective and well tolerated, and where new therapy is required sulindac may fit the bill. , GENERAL-PRACTICE PRESCRIBING DOCTORS need education and guidance in the pre- scribing of drugs and medicines.3 Parish and his col- leagues in Swansea are looking at some of the factors 1 Clinoril in the Treatment of Rheumatic Disorders. Proceedings of a Sym- posium held at the VIII European Rheumatology Congress, Helsinki, 1-7 June, 1975. New York, 1976. 2. Dieppe, P A., Burry, H. C., Grahame, R., Perera, T. Rheumatol. Rehab. 1976, 15, 112. 3 Lancet, 1976, ii, 351. that determine prescribing habits. In a cohort of doctors who entered general practice in England and Wales between July, 1969 and July, 1970, they are examining, in particular, previous medical training and experience in relation to prescribing activity, sources of drug infor- mation, and their views on drug advertisements, pre- scription-writing by ancillary staff, the role of the phar- macist in drug treatment, and the matter of high-cost prescribers. Unfortunately, much of the information is obtained by questionnaires (with their inherent limita- tions) rather than by personal interview, but in a prelim- inary report4 some potentially valuable information already emerges. Although there are now plenty of opportunities for training in general practice, most of these doctors had had no such planned training: previous postgraduate ex- perience in general practice seemed to have been haphaz- ard and few had been attached to a general practice as undergraduates. Nearly one in three had qualified out- side the United Kingdom, and these had previously gained less experience in general practice and had com- pleted more short-term postregistration house appoint- ments than their U.K.-trained colleagues. Overseas- trained doctors prescribed a higher proportion of proprietary branded preparations-a tendency which was less for doctors who qualified before 1960, suggest- ing that length of time since qualifying may be a factor here. In 90% of the doctors’ responses to the questionnaire, drug-company representatives were said to be important in making known the existence of a drug, but the most helpful information about usefulness seemed to come from within the profession-from partners, colleagues, consultants, and articles in medical journals and Pre- scriber’s Journal. Unfortunately, Drug and Therapeutics Bulletin, which has the particular virtue ’of giving some guide to cost-effectiveness of treatment,3 was little used by this group of practitioners. But it is encouraging that most practitioners in the survey looked with a critical eye upon information from drug-company representatives and placed more reliance on experience-based advice from professional colleagues and disinterested sources. A group of "high-cost" prescribers were identified who had been investigated for this reason by the Department of Health. In age, sex, and qualifications they did not differ from lower-cost prescribers, but they did include an excess of overseas-trained doctors. Most of these high-cost prescribers felt that the Department was too concerned with prescribing costs, but they did express more eagerness than the others for further training and more information on drug prescribing. If these early observations are confirmed by the 1976 survey, which is now being analysed, the implications will be wide. The proliferation of health centres, in which general practice partners together with pharma- cist colleagues are able to discuss drug treatment regimens, should make an impact on patterns of pre- scribing over the next few years. The influence of pre- vious training in general practice emphasises, once more, that graduate clinical training is just as important in this specialty as in other branches of clinical prac- tice. ** 4. Jl R. Coll Gen Practit 1976, 26, suppl. 1. 5 Committee of Inquiry into the Regulation of the Medical Profession. H.M. Stationery Office, 1975

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excreted primarily in the urine. Three main substancesemerge in the urine-the unchanged drug, its sulphonederivative, and a dihydroxylated derivative. A sulphidemetabolite with a long half-life is present in plasma butnot urine, probably because of extensive binding to

plasma proteins. In several anti-inflammatory assays,the sulphide metabolite has been shown to be as activeas indomethacin.Sulindac (’Clinoril’) was the subject of a special sym-

posium at the VIII European Rheumatology Congress,Helsinki, Finland, in June, 1975. Eighteen papers readat that symposium have now been published,’ and theydeal with the pharmacology of sulindac and the efficacyof this drug versus aspirin, ibuprofen, phenylbutazone,and oxyphenbutazone. In osteoarthritis, rheumatoidarthritis, ankylosing spondylitis, gout, and acute painfulshoulder, sulindac seems to be as effective and in manyinstances better tolerated than the other drugs. Fewreports have appeared in the U.K. journals, but oneclinical triaP comparing sulindac (400 mg/day) withibuprofen (1200 mg/day) in osteoarthrosis of the hipshowed that the two drugs were much the same in termsof patient and doctor preference, effects on hip move-ments, and toxicity. No serious side-effects were encoun-tered, and the analgesic properties of sulindac weresuperior to those of ibuprofen.

Like all anti-inflammatory drugs, sulindac should beused with caution in patients with a history of gastro-intestinal upset, and since the drug is excreted largelyvia the kidneys the dosage should be reduced in renalimpairment. It is known that steroids, especially thosecontaining fluorine (e.g., triamcinolone), may produce amyopathy, but no muscle cramps or myopathies haveoccurred during four years of clinical trials with sulin-dac. Side-effects do not seem to be as frequent as withindomethacin, but these are early days. The maximumdose administered to date has been 400 mg/day, butwider clinical experience may well reveal that this doseis insufficient in certain rheumatic conditions.One of the advantages of sulindac is that it need be

given only twice-a-day. Each tablet of clinoril contains100 mg of sulindac and the recommended dosage is100-200 mg twice-a-day. The rheumatologist or generalpractitioner in the U.K. can be excused for taking a cau-tious attitude to a new anti-inflammatory agent. With somany non-steroidal anti-inflammatory drugs to choosefrom, and many of the patients taking more’than onepreparation, it will be a long time before we know thetrue worth of sulindac. Existing evidence suggests thatit is effective and well tolerated, and where new therapyis required sulindac may fit the bill. ,

GENERAL-PRACTICE PRESCRIBING

DOCTORS need education and guidance in the pre-scribing of drugs and medicines.3 Parish and his col-leagues in Swansea are looking at some of the factors

1 Clinoril in the Treatment of Rheumatic Disorders. Proceedings of a Sym-posium held at the VIII European Rheumatology Congress, Helsinki, 1-7June, 1975. New York, 1976.

2. Dieppe, P A., Burry, H. C., Grahame, R., Perera, T. Rheumatol. Rehab.1976, 15, 112.

3 Lancet, 1976, ii, 351.

that determine prescribing habits. In a cohort of doctorswho entered general practice in England and Walesbetween July, 1969 and July, 1970, they are examining,in particular, previous medical training and experiencein relation to prescribing activity, sources of drug infor-mation, and their views on drug advertisements, pre-scription-writing by ancillary staff, the role of the phar-macist in drug treatment, and the matter of high-costprescribers. Unfortunately, much of the information isobtained by questionnaires (with their inherent limita-tions) rather than by personal interview, but in a prelim-inary report4 some potentially valuable information

already emerges.Although there are now plenty of opportunities for

training in general practice, most of these doctors hadhad no such planned training: previous postgraduate ex-perience in general practice seemed to have been haphaz-ard and few had been attached to a general practice asundergraduates. Nearly one in three had qualified out-side the United Kingdom, and these had previouslygained less experience in general practice and had com-pleted more short-term postregistration house appoint-ments than their U.K.-trained colleagues. Overseas-trained doctors prescribed a higher proportion of

proprietary branded preparations-a tendency whichwas less for doctors who qualified before 1960, suggest-ing that length of time since qualifying may be a factorhere.

In 90% of the doctors’ responses to the questionnaire,drug-company representatives were said to be importantin making known the existence of a drug, but the mosthelpful information about usefulness seemed to comefrom within the profession-from partners, colleagues,consultants, and articles in medical journals and Pre-scriber’s Journal. Unfortunately, Drug and TherapeuticsBulletin, which has the particular virtue ’of giving someguide to cost-effectiveness of treatment,3 was little usedby this group of practitioners. But it is encouraging thatmost practitioners in the survey looked with a critical eyeupon information from drug-company representativesand placed more reliance on experience-based advicefrom professional colleagues and disinterested sources. Agroup of "high-cost" prescribers were identified whohad been investigated for this reason by the Departmentof Health. In age, sex, and qualifications they did notdiffer from lower-cost prescribers, but they did includean excess of overseas-trained doctors. Most of these

high-cost prescribers felt that the Department was tooconcerned with prescribing costs, but they did expressmore eagerness than the others for further training andmore information on drug prescribing.

If these early observations are confirmed by the 1976survey, which is now being analysed, the implicationswill be wide. The proliferation of health centres, in

which general practice partners together with pharma-cist colleagues are able to discuss drug treatment

regimens, should make an impact on patterns of pre-scribing over the next few years. The influence of pre-vious training in general practice emphasises, once

more, that graduate clinical training is just as importantin this specialty as in other branches of clinical prac-tice. **

4. Jl R. Coll Gen Practit 1976, 26, suppl. 1.5 Committee of Inquiry into the Regulation of the Medical Profession. H.M.

Stationery Office, 1975