Skip to main content
Log in

Adverse Drug Reactions

An Overview of Special Considerations in the Management of the Elderly Patient

  • Review Article
  • Drug Experience
  • Published:
Drug Safety Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

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

    Article  PubMed  CAS  Google Scholar 

  • 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

    CAS  Google Scholar 

  • Antal EJ, Kramer PA, Mercik SA, Chapron DJ, Lawson IR. Theophylline pharmacokinetics in advanced age. British Journal of Clinical Pharmacology 12: 637–645, 1981

    Article  PubMed  CAS  Google Scholar 

  • Ashour M, Salama FD, Morris A, Skinner J. Acute dysphagia induced by bendrofluazide-K. Practitioner 228: 524–525, 1984

    PubMed  CAS  Google Scholar 

  • Baillie SP, Bateman N, Coates PE, Woodhouse KW. Age and pharmacokinetics of morphine. Age and Ageing 18: 258–262, 1989

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    CAS  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Brater DG, Day B, Burdettle A, Anderson S. Bumetamide and frusemide in heart failure. Kidney International 26: 183–189, 1984

    Article  PubMed  CAS  Google Scholar 

  • Briggs RS, Castleden CM, Kraft CA. Improved hypnotic treatment using chloromethazole and temazepam. British Medical Journal (1): 601–604, 1980

    Article  Google Scholar 

  • Caranasos GJ, Stewart RB, Cluff LE. Drug-induced illness leading to hospitalization. Journal of the American Medical Association 228: 713–717, 1974

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Cartwright A, Smith C. Elderly people, their medicines and their doctors, Routledge, London, 1988

    Google Scholar 

  • Castleden CM, George CF. The effect of ageing on the hepatic clearance of propanolol. British Journal of Clinical Pharmacology 7: 49–54, 1979

    Article  PubMed  CAS  Google Scholar 

  • 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

    Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 16: 31–41, 1976

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Fennerty A, Campbell IA, Routledge PA. Anticoagulants in venous thromboembolism. British Medical Journal 297: 1285–1287, 1988

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Granerus AK. Factors influencing the occurrence of ‘on-off symptoms during long term treatment with L-dopa. Acta Medica Scandinavica 203: 75–85, 1978

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  Google Scholar 

  • Hurwitz N. Predisposing factors in adverse reactions to drugs. British Medical Journal 1: 536–539, 1969

    Article  PubMed  CAS  Google Scholar 

  • Hurwitz N, Wade OL. Intensive hospital monitoring of adverse reactions to drugs. British Medical Journal 1: 531–536, 1969

    Article  PubMed  CAS  Google Scholar 

  • Ibrahim IK, Ritch AES, Maclennan WJ, May T. Are potassium supplements for the elderly necessary? Age and Ageing 7: 165–170, 1978

    Article  PubMed  CAS  Google Scholar 

  • Inman WHW. Study of fatal bone marrow depression with special reference to phenylbutazone and oxyphenbutazone. British Medical Journal 1: 1500–1505, 1977

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  Google Scholar 

  • Johnston GD, McDevitt DG. Is maintenance digoxin necessary in patients with sinus rhythm? Lancet 1: 567–570, 1979

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Klein K, Murray GR, Laake K. Pharmacokinetics of temazepam in geriatric patients. European Journal of Clinical Pharmacology 30: 745–747, 1986

    Article  Google Scholar 

  • Klein LE, German PS, Levine DM, Feroli R, Ardery J. Medication problems among outpatients. Archives in Internal Medicine 144: 1185–1188, 1984

    Article  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Koch-Weser J, Greenblatt DJ, Sellers EM, Shader RI. Drug disposition in old age. New England Journal of Medicine 306: 1081–1088, 1982

    Article  Google Scholar 

  • Law R, Chalmers C. Medicines and elderly people: a general practice survey. British Medical Journal 1: 565–568, 1976

    Article  PubMed  CAS  Google Scholar 

  • Lawson DH. Adverse reactions to potassium chloride. Quarterly Journal of Medicine 43: 433–440, 1974

    PubMed  CAS  Google Scholar 

  • Lipworth BJ, Tregaskis BF, McDevitt DG. Beta adrenoreceptor responses to inhaled salbutamol in the elderly. British Journal of Clinical Pharmacology 28: 725–729, 1989

    Article  PubMed  CAS  Google Scholar 

  • 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

    Google Scholar 

  • Martys CR. Adverse reactions to drugs in general practice. British Medical Journal 2: 1194–1197, 1979

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Miller AC, Ader J, Vestal RE. Effect of age on the pharmacokinetics of tolbutamide in man. Pharmacologist 19: 128, 1977

    Google Scholar 

  • Miller RR. Drug surveillance utilizing epidemiological methods. American Journal of Hospital Pharmacology 30: 584–592, 1973

    CAS  Google Scholar 

  • Myers MG. Hydrochlorothiazide with or without amiloride for hypertension in the elderly. Archives in Internal Medicine 147: 1026–1030, 1987

    Article  CAS  Google Scholar 

  • Nation RL, Triggs EJ, Selig M. Lignocaine kinetics in cardiac patients and aged subjects. British Journal of Clinical Pharmacology 4: 439–448, 1977

    Article  PubMed  CAS  Google Scholar 

  • National Heart Foundation of Australia. Treatment of mild hypertension in the elderly. Medical Journal of Australia 2: 398–402, 1981

    Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Google Scholar 

  • Park GR, Shelly MP, Quinn K, Roberts P. Dihydrocodeine — a reversible cause of renal failure? European Journal of Anaesthesiology 6: 303–314, 1989

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  Google Scholar 

  • Pickles H. Prescriptions, adverse reactions and the elderly. Lancet 1: 40–41, 1986

    Article  Google Scholar 

  • Prudham D, Grimley-Evans J. Factors associated with falls in the elderly; a community study. Age and Ageing 10: 141–146, 1981

    Article  PubMed  CAS  Google Scholar 

  • Ramsay LE, Boyle P, Ramsay MH. Factors influencing serum potassium in treated hypertension. Quarterly Journal of Medicine 184: 401–410, 1977

    Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Rubin P. Editorial comment. British Medical Journal 297: 1260, 1988

    Article  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Rubin PC, Scott PJW, Reid JL. Prazosin disposition in young and elderly subjects. British Journal of Clinical Pharmacology 12: 401–404, 1981

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Scott PJW. Anticoagulant drugs in the elderly: the risks usually out-weigh the benefits. British Medical Journal 297: 1261–1263, 1988

    Article  PubMed  CAS  Google Scholar 

  • 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

    Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Skander MP, Ryan FP. Non-steroidal anti-inflammatory drugs and pain free peptic ulceration in the elderly. British Medical Journal 297: 833–834, 1988

    Article  PubMed  CAS  Google Scholar 

  • Smith T, Haber E. Digoxin intoxication: the relation of clinical presentation to serum digoxin concentration. Journal of Clinical Investigation 49: 2377–2386, 1970

    Article  PubMed  CAS  Google Scholar 

  • Somerville K, Faulkner G, Langman M. Non-steroidal anti-inflammatory drugs and bleeding peptic ulcer. Lancet 1: 462–464, 1986

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Stephen PJ, Williamson J. Drug induced Parkinsonism in the elderly. Lancet 2: 1082–1083, 1984

    Article  PubMed  CAS  Google Scholar 

  • Sunderam SG, Mankikar GD. Hyponatraemia in the elderly. Age and Ageing 12: 77–80, 1983

    Article  PubMed  CAS  Google Scholar 

  • 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

    Google Scholar 

  • Toner JM, Ramsay LE. Thiazide-induced hypokalaemia: prevalence higher in women. British Journal of Clinical Pharmacology 18: 449–452, 1984

    Article  PubMed  CAS  Google Scholar 

  • 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

    Google Scholar 

  • Vestal RE, Wood AJJ, Shand DG. Reduced beta-adrenoreceptor sensitivity in the elderly. Clinical Pharmacology and Therapeutics 26: 181–186, 1979

    PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Weber JCP, Griffin JP. Prescriptions, adverse reactions and the elderly. Lancet 1: 1220, 1986

    Article  PubMed  CAS  Google Scholar 

  • Wickramasinghe LSP, Basu SK, Bansal SK. Long-term oral anticoagulant therapy in elderly patients. Age and Ageing 17: 388–396, 1988

    Article  PubMed  CAS  Google Scholar 

  • Williamson J, Chopin JM. Adverse reactions to prescribed drugs in the elderly: a multi-centre investigation. Age and Ageing 9: 73–80, 1980

    Article  PubMed  CAS  Google Scholar 

  • 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

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Brawn, L.A., Castleden, C.M. Adverse Drug Reactions. Drug-Safety 5, 421–435 (1990). https://doi.org/10.2165/00002018-199005060-00003

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00002018-199005060-00003

Keywords

Navigation