Summary
The incidence of adverse drug reactions increases with aging, and the elderly are more likely to suffer serious or fatal reactions. Thus, morbidity and mortality are considerable in old patients, with 15% of those in hospital suffering a reaction, and many admitted as a consequence of one.
The greater propensity of older patients for adverse drug reactions largely reflects the prescription of drugs to them, although over-the-counter purchases must also play a part. The elderly take more drugs per se (which is a reflection of multiple pathology), and more drugs with a narrow therapeutic index associated with a high risk of dangerous adverse reactions and drug interactions. They also have a reduced ability to withstand any reactions due to concomitant disease, and an altered pharmacokinetic and -dynamic response which tends to increase drug effects.
The recommendation must be to use fewer drugs in older patients, perhaps trying alternative medicine first in nonacute conditions. Starting doses can often be reduced in the elderly, and clinical and therapeutic monitoring of effect is mandatory.
The use of diuretics, antihypertensives, anti-Parkinsonian drugs and anticoagulants emphasise these points, and is discussed in detail together with digoxin, analgesics and nonsteroidal anti-inflammatory drugs. Clear guidelines are given for the use of each of these classes of drug.
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References
Adams DH, Howie AJ, Michal J, McConkey B, Bacon PA, et al. Non-steroidal anti-inflammatory drugs and renal failure. Lancet 1: 57–60, 1986
Adams KRH, Al-Hamouz S, Edmund E, Tallis RG, Vellodi C, et al. Inappropriate prescribing in the elderly. Journal of the Royal College of Physicians 21: 39–41, 1987
Antal EJ, Kramer PA, Mercik SA, Chapron DJ, Lawson IR. Theophylline pharmacokinetics in advanced age. British Journal of Clinical Pharmacology 12: 637–645, 1981
Ashour M, Salama FD, Morris A, Skinner J. Acute dysphagia induced by bendrofluazide-K. Practitioner 228: 524–525, 1984
Baillie SP, Bateman N, Coates PE, Woodhouse KW. Age and pharmacokinetics of morphine. Age and Ageing 18: 258–262, 1989
Blake AJ, Morgan K, Bendall MJ, Dallosso H, Ebrahim SBJ, et al. Falls by elderly people at home: prevalence and associated factors. Age and Ageing 17: 365–372, 1988
Birkmayer W, Birkmayer GD. Effect of (−) deprenyl in the longterm treatment of Parkinson’s disease. A 10-year experience. Journal of Neurological Transmission 22 (Suppl.): 219–225, 1986
Birtel O, Buhler FR, Kiowski W, Lutold B. Decreased beta-adrenoreceptor responsiveness as related to age, blood pressure and plasma catecholamines in patients with essential hypertension. Hypertension 2: 130–138, 1980
Brater DG, Chennavasin P, Seiwell R. Frusemide in patients with heart failure: shift in dose response curves. Clinical Pharmacology and Therapeutics 28: 182–186, 1980
Brater DG, Day B, Burdettle A, Anderson S. Bumetamide and frusemide in heart failure. Kidney International 26: 183–189, 1984
Briggs RS, Castleden CM, Kraft CA. Improved hypnotic treatment using chloromethazole and temazepam. British Medical Journal (1): 601–604, 1980
Caranasos GJ, Stewart RB, Cluff LE. Drug-induced illness leading to hospitalization. Journal of the American Medical Association 228: 713–717, 1974
Carlsen JE, Kpber L, Torp-Pedersen C, Johansen P. Relation between dose of bendrofluazide, antihypertensive effect and adverse biochemical effects. British Medical Journal 300: 975–978, 1990
Carson JL, Strom BL, Soper KA, West SL. The association of NSAIDs with upper gastrointestinal tract bleeding. Archives in Internal Medicine 147: 85–88, 1987
Cartwright A, Smith C. Elderly people, their medicines and their doctors, Routledge, London, 1988
Castleden CM, George CF. The effect of ageing on the hepatic clearance of propanolol. British Journal of Clinical Pharmacology 7: 49–54, 1979
Castleden CM, George CF. Prescriptions for the elderly. In O’Malley (Ed.) Clinical pharmacology and drug treatment in the elderly, pp, 71–98, Churchill Livingstone, London, 1984
Castleden CM, Pickles HP. Suspected adverse drug reactions in elderly patients reported to the committee on safety of medicines. British Journal of Clinical Pharmacology 26: 347–353, 1988
Castleden CM, Swift CG. Hypnotics, sedatives and anticonvulsants. In Swift (Ed.) Clinical pharmacology in the elderly, pp. 281–342, Marcel Dekker Inc., New York, 1987
Chaudry AY, Bing RF, Castleden CM, Swales JP, Napier CJ. The effect of ageing on the response to frusemide in normal subjects. European Journal of Clinical Pharmacology 27: 303–306, 1984
Cleland JGF, Dargie HJ, McAlpine H, Ball SG, Morton JJ, et al. Severe hypotension after first dose of enalapril in heart failure. British Medical Journal 291: 1309–1312, 1985
Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 16: 31–41, 1976
Committee of Safety of Medicines. Current Problems No. 15, 1985
Coope J, Warrender TS. Randomised trial of treatment of hypertension in elderly patients in primary care. British Medical Journal 293: 1145–1151, 1986
Cusack B, Kelly J, O’Malley K, Noel J, Lavan J, et al. Digoxin in the elderly: pharmacokinetic consequence of old age. Clinical Pharmacology and Therapeutics 25: 772–776, 1979
Davies KN, Castleden CM, McBurney A, Jagger C. The effect of ageing on the pharmacokinetics of dihydrocodeine. European Journal of Clinical Pharmacology 37: 375–379, 1989
Ehsanullah RSB, Page MC, Tildesley G, Wood JR. Prevention of gastroduodenal damage induced by non-steroidal anti-inflammatory drugs: controlled trial of ranitidine. British Medical Journal 297: 1017–1021, 1988
European Working Party. Antihypertensive therapy in patients above age 60 years: fourth interim report of the EWPHE. Clinical Science and Molecular Medicine 55: 263s–270s, 1978
Farquharson-Roberts MA, Giddings AEB, Nunn AJ. Perforation of small bowel due to slow-release potassium chloride (slow K). British Medical Journal 3: 206, 1975
Fennerty A, Campbell IA, Routledge PA. Anticoagulants in venous thromboembolism. British Medical Journal 297: 1285–1287, 1988
Fieldman PD, Limbird LE, Nadeau J. Alterations in leukocyte beta-receptor affinity with aging: a potential explanation for altered beta adrenergic sensitivity in the elderly. New England Journal of Medicine 310: 815–819, 1984
Flanagan RJ, Johnston A, White AST, Crome P. Pharmacokinetics of dextropropoxyphene and nordextropropoxyphene in young and elderly volunteers after single and multiple dosage. British Journal of Clinical Pharmacology 28: 463–469, 1989
Fletcher A, Beevers DG, Bulpitt CJ, Butler A, Coles EC, et al. The relationship between a low treated blood pressure and IHD mortality: a report from the DHSS Hypertension Care Computing Project (DHCCP). Journal of Human Hypertension 2: 11–15, 1988
Graham DY, Agarwal NM, Roth SH. Prevention of NSAID-induced gastric ulcer with misoprostol: multicentre double-blind placebo controlled trial. Lancet 2: 1277–1279, 1988
Granerus AK. Factors influencing the occurrence of ‘on-off symptoms during long term treatment with L-dopa. Acta Medica Scandinavica 203: 75–85, 1978
Hewick DS, Shaw V. Tissue distribution of radioactivity after injection of [14C]-nitrazepam in young and old rats. Journal of Pharmacology 30: 318–319, 1978 Hollenberg NK, Bannon JA. The PACT study: post-marketing surveillance in 47,465 patients treated with Maxzide (triamterene/hydrochlorothiazide). Americal Journal of Medicine 80 (Suppl. 4A): 30–36, 1986
Hulley SB, Furberg CP, Gurland B, McDonald R, Perry HM, et al. Systolic hypertension in the elderly program (SHEP): anti-hypertensive effect efficacy of chlorthalidone. American Journal of Cardiology 59: 913–920, 1985
Hurwitz N. Predisposing factors in adverse reactions to drugs. British Medical Journal 1: 536–539, 1969
Hurwitz N, Wade OL. Intensive hospital monitoring of adverse reactions to drugs. British Medical Journal 1: 531–536, 1969
Ibrahim IK, Ritch AES, Maclennan WJ, May T. Are potassium supplements for the elderly necessary? Age and Ageing 7: 165–170, 1978
Inman WHW. Study of fatal bone marrow depression with special reference to phenylbutazone and oxyphenbutazone. British Medical Journal 1: 1500–1505, 1977
Jackson PR, Ramsay LE, Wakefield V. Relative potency of spironolactone, triamterene and potassium chloride in thiazide induced hypokalaemia. British Journal of Clinical Pharmacology 14: 257–263, 1982
Joglekar M, Mohanaruban K, Bayer AJ, Pathy MSJ. Can old people on anticoagulants be safely managed as outpatients? Postgraduate Medical Journal 64: 775–777, 1988
Johnston GD, Harron DWG, McDevitt DG. Can digoxin prescribing be improved? A comparison between intuitive and assisted dose selection. European Journal of Clinical Pharmacology 16: 229–235, 1979
Johnston GD, McDevitt DG. Is maintenance digoxin necessary in patients with sinus rhythm? Lancet 1: 567–570, 1979
Judge TG, Caird FI, Leask RGS, Macleod CC. Dietary intake and urinary excretion of potassium in the elderly. Age and Ageing 3: 167–173, 1974
Junios JL, Fabbrini G, Mouradian MM, Chase TN. Controlled release levodopa-carbidopa in the management of Parkinsonian motor fluctuations. Archives of Neurology 44: 1010–1012, 1986
Kellaway GSM, McCrae E. Intensive monitoring for adverse drug effects in patients discharged from acute medical wards. New Zealand Medical Journal 78: 525–528, 1973
Kerremans LM, Tan Y, van Baarst T, van Ginneken M, Gribnau FWJ. Frusemide kinetics and dynamics in aged patients. Clinical Pharmacology and Therapeutics 34: 181–189, 1983
Klein K, Murray GR, Laake K. Pharmacokinetics of temazepam in geriatric patients. European Journal of Clinical Pharmacology 30: 745–747, 1986
Klein LE, German PS, Levine DM, Feroli R, Ardery J. Medication problems among outpatients. Archives in Internal Medicine 144: 1185–1188, 1984
Klotz U, Avant GR, Hoyumpa A, Schentor S, Wilkinson GR. The effects of age and liver disease on the disposition of diazepam in adult men. Journal of Clinical Investigation 55: 347–359, 1975
Koch-Weser J, Greenblatt DJ, Sellers EM, Shader RI. Drug disposition in old age. New England Journal of Medicine 306: 1081–1088, 1982
Law R, Chalmers C. Medicines and elderly people: a general practice survey. British Medical Journal 1: 565–568, 1976
Lawson DH. Adverse reactions to potassium chloride. Quarterly Journal of Medicine 43: 433–440, 1974
Lipworth BJ, Tregaskis BF, McDevitt DG. Beta adrenoreceptor responses to inhaled salbutamol in the elderly. British Journal of Clinical Pharmacology 28: 725–729, 1989
Lumley CE, Walker SR, Hall GC, Staunton N, Grob PR. The under-reporting of adverse drug reactions seen in general practice. Pharmaceutical Medicine 1: 205–212, 1986
Martys CR. Adverse reactions to drugs in general practice. British Medical Journal 2: 1194–1197, 1979
Mattila K, Haavisto M, Rajala S, Heikinheimo R. Blood pressure and five year survival in the very old. British Medical Journal 296: 887–889, 1988
Miller AC, Ader J, Vestal RE. Effect of age on the pharmacokinetics of tolbutamide in man. Pharmacologist 19: 128, 1977
Miller RR. Drug surveillance utilizing epidemiological methods. American Journal of Hospital Pharmacology 30: 584–592, 1973
Myers MG. Hydrochlorothiazide with or without amiloride for hypertension in the elderly. Archives in Internal Medicine 147: 1026–1030, 1987
Nation RL, Triggs EJ, Selig M. Lignocaine kinetics in cardiac patients and aged subjects. British Journal of Clinical Pharmacology 4: 439–448, 1977
National Heart Foundation of Australia. Treatment of mild hypertension in the elderly. Medical Journal of Australia 2: 398–402, 1981
Nolan L, Kenny R, O’Malley K. The need for the reassessment of digoxin prescribing for the elderly. British Journal of Clinical Pharmacology 27: 367–370, 1989
O’Neill CJA, Bowes SG, Sullens CM, Royston JP, Hunt WB, et al. Evaluation of the safety of enalapril in the treatment of heart failure in the very old. British Journal of Clinical Pharmacology 35: 143–150, 1988
Park GR, Shelly MP, Quinn K, Roberts P. Dihydrocodeine — a reversible cause of renal failure? European Journal of Anaesthesiology 6: 303–314, 1989
Perry HM, McDonald RH, Hulley SB, et al. Systolic Hypertension in the Elderly Program — pilot study: morbidity and mortality experiences. Journal of Hypertension 4 (Suppl. 6): s21–s23, 1986
Pickles H. Prescriptions, adverse reactions and the elderly. Lancet 1: 40–41, 1986
Prudham D, Grimley-Evans J. Factors associated with falls in the elderly; a community study. Age and Ageing 10: 141–146, 1981
Ramsay LE, Boyle P, Ramsay MH. Factors influencing serum potassium in treated hypertension. Quarterly Journal of Medicine 184: 401–410, 1977
Robertshaw M, Lai KN, Swaminathan R. Prediction of creatinine clearance from plasma creatinine: comparison of five formulae. British Journal of Clinical Pharmacology 28: 275–280, 1989
Robertson DRC, Walker DG, Renwick AG, George CF. Age related changes in the pharmacokinetics and pharmacodynamics of nifedepine. British Journal of Clinical Pharmacology 25: 297–305, 1988
Robertson DRC, Wood ND, Everest H, Monks K, Waller DG, et al. The effect of age on the pharmacokinetics of levodopa administered alone and in the presence of carbidopa. British Journal of Clinical Pharmacology 28: 61–69, 1989
Rowe JW, Andres R, Tobin JP, Norris AH, Shock NW. The effects of age on creatinine clearance in man: a cross-sectional and longitudinal study. Journal of Gerontology 31: 155–163, 1976
Rubin P. Editorial comment. British Medical Journal 297: 1260, 1988
Rubin PC, Scott PJW, McLean K, Pearson A, Ross D, et al. Atenolol disposition in young and elderly subjects. British Journal of Clinical Pharmacology 13: 235–237, 1982
Rubin PC, Scott PJW, Reid JL. Prazosin disposition in young and elderly subjects. British Journal of Clinical Pharmacology 12: 401–404, 1981
Sabanathan K, Castleden CM, Adam HK, Ryan J, Fitzsimons TJ. A comparative study of the pharmacokinetics and pharmacodynamics of atenolol, hydrochlorothiazide and amiloride in normal young and elderly subjects and elderly hypertensive patients. European Journal of Clinical Pharmacology 32: 53–60, 1987
Scott M, Castleden CM, Adam HK, Smith RP, Fitzsimons TF. The effect of ageing on the disposition of nifedepine and atenolol. British Journal of Clinical Pharmacology 25: 289–296, 1988
Scott PJW. Anticoagulant drugs in the elderly: the risks usually out-weigh the benefits. British Medical Journal 297: 1261–1263, 1988
Seidl LG, Thornton GF, Smith JW, Cluff LE. Studies on the epidemiology of adverse drug reactions III: reactions in patients on a general medical service. Johns Hopkins Medical Bulletin 119: 299–315, 1966
Shepherd AMM, Hewick DS, Moreland TA, Stevenson IH. Age as a determinant of sensitivity to warfarin. British Journal of Clinical Pharmacology 4: 315–320, 1977
Skander MP, Ryan FP. Non-steroidal anti-inflammatory drugs and pain free peptic ulceration in the elderly. British Medical Journal 297: 833–834, 1988
Smith T, Haber E. Digoxin intoxication: the relation of clinical presentation to serum digoxin concentration. Journal of Clinical Investigation 49: 2377–2386, 1970
Somerville K, Faulkner G, Langman M. Non-steroidal anti-inflammatory drugs and bleeding peptic ulcer. Lancet 1: 462–464, 1986
Somogyi A, Hewson D, Muirhead M, Bochner F. Amiloride disposition in geriatric patients: importance of renal function. British Journal of Clinical Pharmacology 29: 1–8, 1990
Staessen J, Bulpitt C, De Leeuw P, Fagard R, Fletcher A, et al. Relation between mortality and treated blood pressure in elderly patients with hypertension: report of the European Working Party on High Blood Pressure in the Elderly. British Medical Journal 298: 1552–1556, 1989
Stephen PJ, Williamson J. Drug induced Parkinsonism in the elderly. Lancet 2: 1082–1083, 1984
Sunderam SG, Mankikar GD. Hyponatraemia in the elderly. Age and Ageing 12: 77–80, 1983
Swift CG. Pharmacodynamics: changes in homeostatic mechanisms, receptor and target organ sensitivity in the elderly. in Denham & George (Eds) Drugs in old age: new perspectives, Vol. 46, pp. 36–52, Churchill Livingstone, London, 1990
Toner JM, Ramsay LE. Thiazide-induced hypokalaemia: prevalence higher in women. British Journal of Clinical Pharmacology 18: 449–452, 1984
Tregaskis DF, Stevenson IH, Pharmacokinetics in old age. In Denham & George (Eds) Drugs in old age: new perspectives, Vol. 46, pp. 9–21, Churchill Livingstone, London, 1990
Vestal RE, Wood AJJ, Shand DG. Reduced beta-adrenoreceptor sensitivity in the elderly. Clinical Pharmacology and Therapeutics 26: 181–186, 1979
Wallis PJW, Lodwick R, Sinha SK, Constable TJ. Effect of naproxen on renal haemodynamics in elderly patients with arthritis. Age and Ageing 18: 26–30, 1989
Weber JCP, Griffin JP. Prescriptions, adverse reactions and the elderly. Lancet 1: 1220, 1986
Wickramasinghe LSP, Basu SK, Bansal SK. Long-term oral anticoagulant therapy in elderly patients. Age and Ageing 17: 388–396, 1988
Williamson J, Chopin JM. Adverse reactions to prescribed drugs in the elderly: a multi-centre investigation. Age and Ageing 9: 73–80, 1980
Wood AJJ, Vestal RE, Williams GR, Branch RA, Shand DG. Effect of ageing and cigarette smoking on antipyrine and in-docyanine green elimination. Clinical Pharmacology and Therapeutics 5: 16–20, 1979
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Brawn, L.A., Castleden, C.M. Adverse Drug Reactions. Drug-Safety 5, 421–435 (1990). https://doi.org/10.2165/00002018-199005060-00003
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DOI: https://doi.org/10.2165/00002018-199005060-00003