1022 Bird

the liver. There is no great evidence to suggest a 5 Vestal R E. Drug use in the elderly: a review ofproblems and genetic linkage to susceptibility for rheumatic special considerations. Dnrgs 19789; 16: 35882. 6 Bender A D. Age and its influence on drug action in adults. Ann Rheum Dis: first published as 10.1136/ard.49.12.1022 on 1 December 1990. Downloaded from diseases such as or rheuma- Drug Information BuUlein 1%9; 3: 153-8. 7 Ewy G A, Kapadia G G, Yao L, Luillin M, Marcus F I. toid arthritis, but increasing evidence is accumu- Digoxin metabolism in the elderly. Cirlation 1969; 39: lating that such oxidative systems can be influenced 449-53. 8 Macklon A F, Barton M, James 0, Rawlins M D. The effect by interleukins, the concentrations of which may ofage on the pharmacokinetics of diazepam. Clin Sci 1980; certainly fluctuate in chronic inflammatory poly- 59: 479-83. 21 Whether the rate ofdrug metabolism 9 Klotz U, Avant G R, Hoyumpa A, Schenker S, Wilkinson arthritis.20 G R. The effects of age and liver disease on the disposition is thereby altered with disease activity, whether and elimination of diazepam in adult man. J Clm Invest the magnitude of this effect if present has clinical 1975; 55: 347-59. 10 Bird H A. The kidney in rheumatic diseases. Ann Rheum Dis relevance, and whether this is accentuated or 1989; 48: 1029-30. reduced in the elderly are all fundamental questions 11 Prescott L F, Leslie P J, Padfield P. Side effects of now requiring resolution. benoxaprofen. Br Med J 1982; 284: 1783. 12 Shedden W I H. Side effects of benoxaprofen. Br Med J Set against this extremely complex background, 1982; 284: 1630. day conference in the 13 Taggart H M, Alderdice J M. Fatal cholestatic jaundice in the 11th Harrogate annual elderly patients taking benoxaprofen. Br Med 7 1982; 284: series 'Growing points in the treatment of rheu- 1372. matic diseases' was devoted to the theme of 14 Woolf A D, Rogers H J, Bradook I D, Corless D. Pharmacokinetic observations on in young 'Antirheumatic drugs in the elderly'. Although it adults, middle aged and elderly patients. Br J Clin has only proved possible to touch the tip of the Pharnaol 1983; 16: 433-7. 15 Bollet A J. Piroxicam serum levels in patients treated iceberg, the ensuing conference report follows. for rheumatic diseases. Semin Arthitis Ahewn 1985; 14 (suppl 1): 25-8. 16 Darrugh A, Gordon A J, Byrne H 0, Hobbs D, Casey E. Single-dose and steady-state pha ma n ofpiroxicam in elderly versus young adults. EurJ Clin Pharmnacol 1985; 28: 305-9. 1 Crooks J. Aging and drug distribution: pharmacodynamics. 17 Richardson C J, Blocka K L N, Ross S G, et al. Effects of age J Chronic Dis 1983; 36: 85-90. and sex on piroxicam dispostion. Cim Pharmncol Ther 2 Stevenson I H, Salem S A M, Shepherd A M M. Studies on 1985; 37: 13-18. drug absorption and metabolism in the elderly. In: Crooks 18 Nebert D W. Clinical pharmacology: possible clinical impor- J, Stevenson I H, eds. Drugs and the elderly. Vol 6. London: tance of genetic differences in drug metabolism. Br MedJ Macmillan, 1979: 51-63. 1981; 283: 537-42. 3 Tozer T N. Concepts basic to pharmacokinetics. Pharncol 19 Sj6gvist F, Alvan G. Aging and drug disposition metabolism. Ther 1981; 12: 109-31. J7ChronicDis 1983; 36: 31-7. 4 Nation R L, Vine J, Triggs E J, Learoyd B. Plasma levels of 20 Dinareilo C A. Interleukin-1 and the pathogenesis of the chlormethiazole and two metabolites after oral administra- acute-phase response. N EnglJ Med 1984; 311: 1413-8. tion to young and aged human beings. Eu J Clin 21 Dinarello C A. Interleukin-1. Ann NY Acad Sci 1988; 546: Pharnacol 1977; 12: 13746. 122-32.

CONFERENCE REPORT*

Antirheumatic drugs in the elderly http://ard.bmj.com/

H A Bird on October 2, 2021 by guest. Protected copyright. An audience of70, drawn from rheumatologists, Although the gastric pH rises and splanchnic geriatricians, pharmacists, paramedicals, and blood flow falls with age, changes in absorption industry, discussed a variety of aspects of drug are probably not important except for drugs treatment in elderly patients with arthritis such as sulphasalazine, which undergo activation during the course of the annual day conference in the gut. During distribution, changes in on 'Antirheumatic drugs in the elderly' held at serum albumin may affect steady state plasma Harrogate on 3 May 1990. concentrations of acidic agents, and disease Papers in the morning session, chaired by Dr modifying antirheumatic drugs might have H A Bird, discussed general aspects of drug greater toxicity. Liver blood flow is reduced, The Uaiersity of Leeds, treatment in the elderly. Dr E Burns, depart- resulting in a decreased ability to metabolise Royal lah Hospital, ment of medicine for the elderly, St James's drugs, though interindividual variation in drug Coewal Road, metabolism caused by environmental pollutants Harropte, University Hospital, Leeds, reviewedage related Nor Yo changes in drug handling in her keynote address. such as tobacco usually outweighs the effects of HG1 2PS The number of 'very elderly' (over 85 years) is aging At excretion, the elimination of hydro- H A Bird increasing, and 15% of the population are now philic drugs is reduced in predictable fashion as with *The deventh in a series of aged over 65. Thirty per cent of all drugs are glomerular filtration rate falls steadily annua day confrences prescribed for the elderly and, with concomitant increasng age. The effect of age on hepatic devoted to the theme in 'Growing ponts in the disease, polypharmacy is often necessary with excretion is less easy to predict, but general tratment of rheumatic its risk of reduced compliance. The pharmaco- there is a reduced clearance of drugs that have a disas' eld at the Yorkshire it Regional Health Authodity, kinetic changes present in the elderly might be high hepatic extraction ratio. In discussion Park Parade, Haroate, summarised under the headings of absorption, was noted that certain subjects seemed to age North Yorkshire, on 3 May 1990. distribution, metabolism, and elimination. faster than others physiologically. It behoved Drugs and the elderly 1023

drug companies to evaluate new compounds in by NSAIDs and the propensity of these drugs to fit and in unfit geriatric groups as well as in cause stricture formation ('diaphragm disease'). Ann Rheum Dis: first published as 10.1136/ard.49.12.1022 on 1 December 1990. Downloaded from those elderly patients receiving other drugs for Much of his work has been done on a group of concomitant disease. patients aged between 55 and 80 years and, in Mr I Buchan, University of Liverpool, discussion, the possibility that this might be an described a survey of drugs received by patients effect related to age was raised as members of attending a regional inpatient rheumatology the audience had found it less commonly in centre. Fifty five out of 100 patients were at risk younger patients. The phenomenon seemed to of interaction as defined by the appendix of the be related to and might be allevi- British National Formulary, but only 11 of these ated by the co-administration of protective had clinical evidence of interaction. Patients or the use of pro-NSAIDs. were receiving a mean of 5 4 drugs. The princi- The afternoon session, chaired by Professor pal consequences ofinteraction were drowsiness, V Wright, dealt in greater depth with renal caused by the simultaneous prescription of two aspects and compliance. Dr J Eccles, St James's , and impaired renal function, possibly University Hospital, Leeds, reviewed the caused by the coprescription of a non-steroidal changes that occur as the kidney ages. Glomeru- anti-inflammatory drug (NSAID) with a diuretic lar filtration rate falls, leading to a fall in tubular or antihypertensive drug. In discussion the need excretion. There is a reduction in the number of forbetteranalgesicsthatlacked a sedativeeffectin glomeruli, some of which are even lost as early the elderly was emphasised. Negative inter- as the seventh month of intrauterine life. Non- actions are also important but tend not to com- steroidal anti-inflammatory drugs were able to mand the attention ofthose interactions that have interact with the kidney at a variety of sites, and clinical consequences. the standard advice to reduce the dose prescribed Drs F Johnston and P McGill, collaborating in the elderly remained valid. from the departments of geriatrics and rheuma- Dr L Simon, Harvard Medical School, tology at Stobhill General Hospital, Glasgow, Boston, Massachusetts, reinforced these prin- surveyed theirexperience with disease modifying ciples with his pharmacokinetic study of drug treatment in the elderly. Thirty seven in elderly patients with mild to elderly patients with moderate renal impairment. After three days receiving disease modifying drugs were assessed washout without NSAIDs, naproxen 375 mg to determine if benefits outweighed risks. A twice daily was given for 14 days. Changes in surprisingly large number of patients received creatinine clearance, serum creatinine, and steroids with benefit. Gold had proved easy to diastolic blood pressure were correlated with use in view of the injection formulation and, changes in serum and urinary provided that adequate precautions were taken, prostaglandins. Serum thromboxane B2 fell and was safe. Azathioprine had been used for its urinary was reduced during steroid reducing properties, and patients receiv- treatment. Nevertheless, diastolic blood pressure ing NSAIDs had developed a variety of side remained unaltered and there was no significant effects as a result of them. It was argued that impairment m creatinine clearance or serum disease modifying drugs, allowing the reduced creatinine. All patients had a baseline creatinine http://ard.bmj.com/ use of NSAIDs in rheumatoid arthritis, were clearance of <70 ml/min or a serum creatinine preferred in the elderly. The risk of oncogenesis of >115 tLmolJl, and it was concluded that was low in this group and the only major naproxen in this dose could be safely prescribed problem, perhaps peculiar to Glasgow, had for patients with impaired renal function. In been the reactivation of tuberculosis following discussion the geriatricians drew attention to the introduction of steroids. the relative normality of these patients and the

Dr A Taggart, Musgrave Park Hospital, additional problems encountered when the on October 2, 2021 by guest. Protected copyright. Belfast, presented a pharmacokinetic study on elderly experienced simultaneous fluid depletion the handling of benorylate in patients with in an acute illness. arthritis. The median half life of free salicylic Mr Buchan, Liverpool, then presented his acid was greater in patients with survey of serum creatnine in a group of (10-6 hours) than in those with rheumatoid arthritic patients with a variety of diagnoses arthritis (7-7 hours). Large differences in the taking either NSAIDs, analgesics, or both. steady state concentration of free and total Although creatinine deteriorated with age, there were found between controls and was no significant difference between serum patients. The average steady state concentration creatinine in patients receiving or not receiving of was greater (p=0 04) in arthritic NSAIDs or in male or female patients matched patients than in controls. The pharmacokinetics for age. This provided further support for the suggested that the increased toxicity associated relative safety of NSAIDs, used in modest with full benorylate dosage in elderly arthritic dosage, provided that there was no simultaneous patients is due partly to reduced clearance but acute illness. mainly to lower body weight. This study further The section on compliance began with a illustrated the need for the adequate evaluation review by Dr T Pullar, General Infirmary at of new drugs in the elderly, the age group for Leeds. Methods available for assessing com- which they were most commonly prescribed, pliance included return tablet count, patient before introduction. interview, pharmacological methods, and elec- The last keynote talk of the morning was tronic monitoring. Return tablet count and given by Dr Ingvar Bjarnason of Northwick interview were subject to certain criticisms, and Park Hospital, who described the changes in pharmacological methods (such as the incor- small intestinal permeability that can be caused poration of a small marker molecule, perhaps a 1024 Bird

subclinical dose of phenobarbitone, in tablets of likely to be taking diuretic or hypnotic drugs.

active drug) were preferred. They were also less Mrs J Hill, Royal Bath Hospital, Harrogate, Ann Rheum Dis: first published as 10.1136/ard.49.12.1022 on 1 December 1990. Downloaded from expensive than electronic monitoring, which described the use of a questionnaire to deter- only indicated opening of the bottle and did not mine what patients knew about the disease and confirm that the tablet had then been taken. An its treatment. Eighteen elderly patients with overview of all such studies suggested that full rheumatoid arthritis knew less than a group of compliance (95-100% ofthe dose reliably taken) younger patients with the same disease, assessed was achieved in 5-20% of patients and sloppy by the same questionnaire. The elderly found compliance (50-90% of each dose taken) was it particularly hard to distinguish between achieved in 40-70% of patients. The number of NSAIDs and disease modifying drugs and often patients showing either low or non-compliance did not known which disease the drugs were was usually less than 10/o. Interestingly, older for. The need to back up patient information patients displayed better compliance with forms provided with tuition was emphasised. In warfarin than younger patients. Whether com- discussion some had found self medication pliance correlated with intelligence in the improved patient knowledge, but only a small elderly, or whether compliance was better with proportion of rheumatic patients enter hospital drugs that made you feel better rather than to participate in this. Information sheets in those that made you feel worse, had not been general needed to be simple, though a propor- adequately studied. tion of patients, perhaps greater than normally Dr Burns (Leeds) had studied cognitive expected, benefited from a more detailed infor- function and patients' knowledge about drug mation sheet. treatment in 207 geriatric outpatients. Patient/ The conference ended with two brief papers doctor agreement on the number of drugs taken by Dr J Young, St Luke's Hospital, Bradford, fell with increasing age, independently ofchange on more clinical aspects. He first reviewed non- in cognitive function, though the patients ability arthritic hip pain in the elderly. In this group a to recall information about drugs was related to differential diagnosis of metastasis, Paget's cognitive function. Many patients said their disease, and fractured neck of femur, even if not knowledge of drugs was inadequate and would apparent by radiography, all needed to be have liked more information. Although the considered as mimics of osteoarthritis at the hip audience was in broad agreement with the joint. Geriatricians were familiar with the 'new findings, there was less agreement on the best braces' sign, indicating recent rapid weight loss, way to improve the provision of information, and the 'new walking stick' sign, indicating an cases being made for its delivery either by the acute onset of recent hip pain even if the history doctor, the pharmacist, or even by a lay was a little confusing. The second paper on the assistant. aging spine reviewed the economic impact of Mrs R Hopkins, General Infirmary at Leeds, back pain found in the elderly who were had also studied awareness of prescribed drugs employed compared with the apparent ameli- in 317 patients. Under the age of 65 more oration of back pain as the patient got older and patients knew details of their drugs and over the left work. Reasons discussed for this included age of 75 only one third of patients studied were retirement, modified pain perception in the http://ard.bmj.com/ able to name the tablets they were taking. elderly, and, possibly, stabilisation of the Seventy five per cent of the over 75s attending lumbar spine as degenerative joint disease inter- rheumatology clinic had been receiving an vened, though it was accepted that this also NSAID. The most elderly were particularly caused back pain in its own right. on October 2, 2021 by guest. Protected copyright.