Hostname: page-component-cd9895bd7-gbm5v Total loading time: 0 Render date: 2024-12-19T18:55:47.837Z Has data issue: false hasContentIssue false
  • English
  • Français

Clinical pharmacology of analgesics in old age and frailty

Part of: Bespoke shallow archive Weizmann

Published online by Cambridge University Press:  06 November 2009

Sarah J Mitchell ,
Sarah N Hilmer  and
Andrew J McLachlan
Sarah J Mitchell
Affiliation:
Sydney Medical School, University of Sydney, Sydney, NSW, Australia Departments of Clinical Pharmacology and Aged Care, Royal North Shore Hospital, Sydney, NSW, Australia
Sarah N Hilmer*
Affiliation:
Sydney Medical School, University of Sydney, Sydney, NSW, Australia Departments of Clinical Pharmacology and Aged Care, Royal North Shore Hospital, Sydney, NSW, Australia
Andrew J McLachlan
Affiliation:
Faculty of Pharmacy, University of Sydney, Sydney, NSW, Australia Centre for Education and Research on Ageing (CERA), Concord Repatriation General Hospital, Concord, NSW, Australia
*
Address for correspondence: Associate Professor Sarah N Hilmer, Departments of Clinical Pharmacology and Aged Care, Ward 11C Main Building, Royal North Shore Hospital, Pacific Highway, St Leonards NSW 2065, Australia. Email: [email protected]
Get access Rights & Permissions [Opens in a new window]

Summary

There is a high prevalence of pain in older people. Optimal assessment and management of pain in this population is challenging. The pharmacokinetics and pharmacodynamics of analgesic medications are affected by ageing and frailty, as well as by intercurrent medical conditions and their treatments. This review describes what is currently understood about the impacts of old age and frailty on the clinical pharmacology of commonly used analgesics, to provide a rational basis for the use of these medicines. In view of the wide age-related inter-individual variability in pharmacokinetics and pharmacodynamics of analgesic medications, monitoring of clinical response and adverse effects is essential to optimize pain control in older people.

Keywords

analgesiapainageingfrailtypharmacology
Type
Clinical geriatrics
Information
Reviews in Clinical Gerontology , Volume 19 , Issue 2 , May 2009 , pp. 103 - 118
Copyright
Copyright © Cambridge University Press 2009

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1American Geriatrics Society (AGS). The management of persistent pain in older persons. AGS Panel on Persistent Pain in Older Persons. JAGS 2002; 50 (6S): S205–24.Google Scholar
2Barber, JB, Gibson, SJ. Treatment of chronic non-malignant pain in the elderly: safety considerations. Drug Safety 2009; 32 (6): 457–74.CrossRefGoogle ScholarPubMed
3Cole, LJ, Farrell, MJ, Gibson, SJ, Egan, GF. Age-related differences in pain sensitivity and regional brain activity evoked by noxious pressure. Neurobiol Aging. Available online 30 May 2008.Google Scholar
4McLachlan, AJ, Hilmer, SN, Le Couteur, DG. Variability in response to medicines in older people: phenotypic and genotypic factors. Clin Pharmacol Ther 2009; 85 (4): 431–3.CrossRefGoogle ScholarPubMed
5Fried, LP, Tangen, CM, Walston, J et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci 2001; 56 (3): M146–56.Google Scholar
6Fox, PL, Raina, P, Jadad, AR. Prevalence and treatment of pain in older adults in nursing homes and other long-term care institutions: a systematic review. CMAJ 1999; 160 (3): 329–33.Google ScholarPubMed
7McLean, AJ, Le Couteur, DG. Aging biology and geriatric clinical pharmacology. Pharmacol Rev 2004; 56 (2): 163–84.CrossRefGoogle ScholarPubMed
8Hilmer, SN. ADME-tox issues for the elderly. Expert Opin Drug Metab Toxicol 2008; 4 (10): 1321–31.Google Scholar
9Hadjistavropoulos, T, Herr, K, Turk, DC et al. An interdisciplinary expert consensus statement on assessment of pain in older persons. Clin J Pain 2007; 23 (1 Suppl): S1–43.Google Scholar
10Avorn, J, Shrank, WH. Adverse Drug Reactions in Elderly People: A substantial cause of preventable illness. BMJ 2008; 336 (7650): 956–7.Google Scholar
11Davis, MP, Srivastava, M. Demographics, assessment and management of pain in the elderly. Drugs Aging 2003; 20 (1): 23–57.Google Scholar
12Herman, AD, Johnson, TM, Ritchie, CS, Parmelee, PA. Pain management interventions in the nursing home: a structured review of the literature. J Am Geriatr Soc 2009; 57 (7): 1258–67.Google Scholar
13Blyth, FM, Rochat, S, Cumming, RG et al. Pain, frailty and comorbidity on older men: The CHAMP study. Pain 2008; 140 (1): 224–30.Google Scholar
14Gnjidic, D, Murnion, BP, Hilmer, SN. Age and opicid analgesia in an acute hospital population. Age Ageing 2008; 37 (6): 699–702.Google Scholar
15Hilmer, SN, Gnjidic, D. The effects of polypharmacy in older adults. Clin Pharmacol Ther 2009; 85 (1): 86–8.Google Scholar
16Gloth, FM. Concerns with chronic analgesic therapy in elderly patients. Am J Med 1996; 101 (1A): 19–24S.Google Scholar
17Scherder, E, Herr, K, Pickering, G, Gibson, S, Benedetti, F, Lautenbacher, S. Pain in dementia. Pain 2009; 145 (3): 276–8.CrossRefGoogle ScholarPubMed
18Auret, K, Schug, SA. Underutilisation of opioids in elderly patients with chronic pain: approaches to correcting the problem. Drugs Aging 2005; 22 (8): 641–54.CrossRefGoogle ScholarPubMed
19Closs, SJ, Barr, B, Briggs, M, Cash, K, Seers, K. A comparison of five pain assessment scales for nursing home residents with varying degrees of cognitive impairment. J Pain Symptom Manag 2004; 27 (3): 196–205.CrossRefGoogle ScholarPubMed
20Gordon, DB. Pain management in the elderly. J Perianesth Nurs 1999; 114 (6): 367–72.CrossRefGoogle Scholar
21Horgas, AL, Elliott, AF, Marsiske, M. Pain assessment in persons with dementia: relationship between self-report and behavioral observation. JAGS 2009; 57 (1): 126–32.Google Scholar
22American Geriatrics Society (AGS). The management of chronic pain in older persons. AGS Panel on Chronic Pain in Older Persons. JAGS 1998; 53 suppl 3: S8–24.Google Scholar
23Nikles, CJ, Yelland, M, Del Mar, C, Wilkinson, D. The role of paracetamol in chronic pain: an evidence-based approach. Am J Therapeut 2005; 12 (1): 80–91.Google Scholar
24Wynne, H. Drug metabolism and ageing. J Br Menopause Soc 2005; 11 (2): 51–6.CrossRefGoogle ScholarPubMed
25Crome, P. What's different about older people? Toxicology 2003; 192 (1): 49–54.Google Scholar
26Fick, DM, Cooper, JW, Wade, WE, Waller, JL, Maclean, JR, Beers, MH. Updating the Beers criteria for potentially inappropriate medication use in older adults: results of a US consensus panel of experts. Arch Intern Med 2003; 163 (22): 2716–24.Google Scholar
27Hilmer, SN, Mager, DE, Simonsick, EM et al. A drug burden index to define the functional burden of medications in older people. Arch Intern Med 2007; 167 (8): 781–7.Google Scholar
28Thomas, MC. Diuretics, ACE inhibitors and NSAIDs – the triple whammy. Med J Aust 2000; 172 (4): 184–5.CrossRefGoogle ScholarPubMed
29Australian and New Zealand College of Anaesthetists (ANZCA) ANZCA. Acute Pain Management: Scientific Evidence, 2nd edn.Melbourne: Australian and New Zealand College of Anaesthetists, 2005.Google Scholar
30Hilmer, SN, McLachlan, AJ, Le Couteur, DG. Clinical pharmacology in the geriatric patient. Fundam Clin Pharmacol 2007; 21 (3): 217–30.Google Scholar
31Hämmerlein, A, Derendorf, H, Lowenthal, DT. Pharmacokinetic and pharmacodynamic changes in the elderly. Clinical implications. Clin Pharmacokinet 1998; 35 (1): 49–64.Google Scholar
32Hilmer, SN, Ford, G. General Principles of Pharmacology. In Halter, JB, Ouslander, JG, Tinetti, M, Studenski, S, High, K, Asthana, S et al. . (eds). Hazzard's Geriatric Medicine & Gerontology, 6th edn.USA: McGraw-Hill, 2009, pp. 99–117.Google Scholar
33Bales, CW, Ritchie, CS. Sarcopenia, weight loss, and nutritional frailty in the elderly. Ann Rev Nutr 2002; 22: 309–23.CrossRefGoogle ScholarPubMed
34Turnheim, K. When drug therapy gets old: pharmacokinetics and pharmacodynamics in the elderly. Experiment Gerontol 2003; 38 (8): 843–53.Google Scholar
35Perera, V, Bajorek, BV, Matthews, S, Hilmer, SN. The impact of frailty on the utilisation of antithrombotic therapy in older patients with atrial fibrillation. Age Ageing 2009; 38 (2): 156–62.Google Scholar
36Wynne, HA, Cope, LH, Herd, B, Rawlins, MD, James, OF, Woodhouse, KW. The association of age and frailty with paracetamol conjugation in man. Age Ageing 1990; 19 (6): 419–24.Google Scholar
37Wynne, HA, Cope, LH, James, OF, Rawlins, MD, Woodhouse, KW. The effect of age and frailty upon acetanilide clearance in man. Age Ageing 1989; 18 (6): 415–8.Google Scholar
38Wynne, HA, Yelland, C, Cope, LH, Boddy, A, Woodhouse, KW, Bateman, DN. The association of age and frailty with the pharmacokinetics and pharmacodynamics of metoclopramide. Age Ageing 1993; 22 (5): 354–9.Google Scholar
39Schwartz, JB. Erythromycin breath test results in elderly, very elderly, and frail elderly persons. Clin Pharmacol Ther 2006; 79 (5): 440–8.Google Scholar
40Myers, RP, Li, B, Fong, A, Shaheen, AA, Quan, H. Hospitalizations for acetaminophen overdose: a Canadian population-based study from 1995 to 2004. BMC Public Health 2007; 7: 143.CrossRefGoogle ScholarPubMed
41Myers, RP, Shaheen, AA, Li, B, Dean, S, Quan, H. Impact of liver disease, alcohol abuse, and unintentional ingestions on the outcomes of acetaminophen overdose. Clin Gastroenterol Hepatol 2008; 6 (8): 918–25.CrossRefGoogle ScholarPubMed
42Bolesta, S, Haber, SL. Hepatotoxicity associated with chronic acetaminophen administration in patients without risk factors. Ann Pharmacother 2002; 36 (2): 331–3.Google Scholar
43Mitchell, SJ, Murnion, BP, Matthews, ST, Hilmer, SN. Hepatotoxicity of therapeutic paracetamol in hospital inpatients: impact of ageing and frailty. J Clin Pharm Ther 2009 (in press, accepted July 2009).Google Scholar
44Kuehn, BM. FDA focuses on drugs and liver damage: labelling and other changes for acetaminophen. JAMA 2009; 302 (4): 369–71.Google Scholar
45Boers, M, Tangelder, MJ, van Ingen, H, Fort, JG, Goldstein, JL. The rate of NSAID-induced endoscopic ulcers increases linearly but not exponentially with age: a pooled analysis of 12 randomised trials. Ann Rheum Dis 2007; 66 (3): 417–8.Google Scholar
46Davies, NM, McLachlan, AJ, Day, RO, Williams, KM. Clinical pharmacokinetics and pharmacodynamics of celecoxib: a selective cyclo-oxygenase-2 inhibitor. Clin Pharmacokinet 2000; 38 (3): 225–42.Google Scholar
47Kean, WF, Rainsford, KD, Kean, IR. Management of chronic musculoskeletal pain in the elderly: opinions on oral medication use. Inflammopharmacology 2008; 16 (2): 53–75.Google Scholar
48Smith, MA, Gray, JD. Age-related differences in sensitivity to the antinociceptive effects of opioids in male rats. Influence of nociceptive intensity and intrinsic efficacy at the mu receptor. Psychopharmacology (Berl) 2001; 156 (4): 445–53.Google Scholar
49Wilder-Smith, OHG. Opioid use in the elderly. Eur J Pain 2005; 9 (2): 137–40.CrossRefGoogle ScholarPubMed
50Chutka, DS, Takahashi, PY, Hoel, RW. Inappropriate medications for elderly patients. Mayo Clin Proc 2004; 79 (1): 122–39.CrossRefGoogle ScholarPubMed
51Brunton, LL, Lazo, JS, Parker, KL. Goodman and Gilman's The Pharmacological Basis of Therapeutics, 11th edn.New York: McGraw Hill, 2006.Google Scholar
52Pergolizzi, J, Boger, RH, Budd, K, Dahan, A, Erdine, S, Hans, G et al. Opioids and the management of chronic severe pain in the elderly: consensus statement of an International Expert Panel with focus on the six clinically most often used World Health Organization Step III opioids (buprenorphine, fentanyl, hydromorphone, methadone, morphine, oxycodone). Pain Pract 2008; 8 (4): 287–313.CrossRefGoogle Scholar
53Grond, S, Sablotzki, A. Clinical pharmacology of tramadol. Clin Pharmacokinet 2004; 43 (13): 879–923.Google Scholar
54Langford, R, McKenna, F, Ratcliffe, S, Vojtassak, J, Richarz, U. Transdermal fentanyl for improvement of pain and functioning in osteoarthritis: a randomized, placebo-controlled trial. Arthritis Rheum 2006; 54 (6): 1829–37.Google Scholar
55Cone, EJ, Gorodetzky, CW, Yousefnejad, D, Buchwald, WF, Johnson, RE. The metabolism and excretion of buprenorphine in humans. Drug Metab Disposit 1984; 12 (5): 577–81.Google Scholar
56Boger, RH. Renal impairment: a challenge for opioid treatment? The role of buprenorphine. Palliat Med 2006; 20 suppl 1: S17–23.Google Scholar
57Lotrich, FE, Pollock, BG. Aging and clinical pharmacology: implications for antidepressants. J Clin Pharmacol 2005; 45 (10): 1106–22.CrossRefGoogle ScholarPubMed
58Ben-Menachem, E. Pregabalin pharmacology and its relevance to clinical practice. Epilepsia 2004; 45 suppl 6: 13–18.Google Scholar
59Kinirons, MT, Crome, P, Kinirons, MT, Crome, P. Clinical pharmacokinetic considerations in the elderly. An update. Clin Pharmacokinet 1997; 33 (4): 302–12.Google Scholar
60Klotz, U. Effect of age on pharmacokinetics and pharmacodynamics in man. Int J Clin Pharmacol Ther 1998; 36 (11): 581–5.Google Scholar
61Bannwarth, B, Pehourcq, F, Lagrange, F, Matoga, M, Maury, S, Palisson, M et al. Single and multiple dose pharmacokinetics of acetaminophen (paracetamol) in polymedicated very old patients with rheumatic pain. J Rheumatol 2001; 28 (1): 182–4.Google Scholar
62Divoll, M, Abernethy, DR, Ameer, B, Greenblatt, DJ. Acetaminophen kinetics in the elderly. Clin Pharmacol Therapeut 1982; 31 (2): 151–6.Google Scholar
63Barkin, RL, Barkin, SJ, Barkin, DS. Perception, assessment, treatment, and management of pain in the elderly. Clin Geriatr Med 2005; 21 (3): 465–90.CrossRefGoogle ScholarPubMed
64Ho, PC, Triggs, EJ, Bourne, DW, Heazlewood, VJ. The effects of age and sex on the disposition of acetylsalicylic acid and its metabolites. Br J Clin Pharmacol 1985; 19 (5): 675–84.Google Scholar
65Williams, FM, Wynne, H, Woodhouse, KW, Rawlins, MD. Plasma aspirin esterase: the influence of old age and frailty. Age Ageing 1989; 18 (1): 39–42.Google Scholar
66Davies, NM, Skjodt, NM. Choosing the right nonsteroidal anti-inflammatory drug for the right patient: a pharmacokinetic approach. Clin Pharmacokinet 2000; 38 (5): 377–92.CrossRefGoogle ScholarPubMed
67Netter, P, Faure, G, Regent, MC, Procknal, JA, Levy, G. Salicylate kinetics in old age. Clin Pharmacol Ther 1985; 38 (1): 6–11.Google Scholar
68Greenblatt, DJ, Abernethy, DR, Matlis, R, Harmatz, JS, Shader, RI. Absorption and disposition of ibuprofen in the elderly. Arthritis Rheum 1984; 27 (9): 1066–9.CrossRefGoogle ScholarPubMed
69Patrignani, P, Tacconelli, S, Sciulli, MG, Capone, ML. New insights into COX-2 biology and inhibition. Brain Res Brain Res Rev 2005; 48 (2): 352–9.Google Scholar
70Shah, RR. Drug development and use in the elderly: search for the right dose and dosing regimen (Parts I and II). Br J Clin Pharmacol 2004; 58 (5): 452–69.Google Scholar
71Glare, PA, Walsh, TD. Clinical pharmacokinetics of morphine. Ther Drug Monit 1991; 13 (1): 1–23.Google Scholar
72Hutchison, LC, O'Brien, CE. Changes in pharmacokinetics and pharmacodynamics in the elderly patient. J Pharm Prac 2007; 20 (1): 4–12.CrossRefGoogle Scholar
73Lugo, RA, Kern, SE. The pharmacokinetics of oxycodone. J Pain Pall Care Pharmacother 2004; 18 (4): 17–30.Google ScholarPubMed
74Liukas, A, Kuusniemi, K, Aantaa, R et al. Plasma concentrations of oral oxycodone are greatly increased in the elderly. Clin Pharmacol Ther 2008; 84 (4): 462–7.Google Scholar
75Bentley, JB, Borel, JD, Nenad, RE Jr, Gillespie, TJ. Age and fentanyl pharmacokinetics. Anesth Analg 1982; 61 (12): 968–71.Google Scholar
76Johnson, RE, Fudala, PJ, Payne, R. Buprenorphine: considerations for pain management. J Pain Symptom Manage 2005; 29 (3): 297–326.Google Scholar
77Spina, E, Scordo, MG. Clinically significant drug interactions with antidepressants in the elderly. Drugs Aging 2002; 19 (4): 299–320.CrossRefGoogle ScholarPubMed
78Sommer, BR, Fenn, HH, Ketter, TA. Safety and efficacy of anticonvulsants in elderly patients with psychiatric disorders: oxcarbazepine, topiramate and gabapentin. Expert Opin Drug Saf 2007; 6 (2): 133–45.CrossRefGoogle ScholarPubMed
79Randinitis, EJ, Posvar, EL, Alvey, CW, Sedman, AJ, Cook, JA, Bockbrader, HN. Pharmacokinetics of pregabalin in subjects with various degrees of renal function. J Clin Pharmacol 2003; 43 (3): 277–83.Google Scholar
80Garnett, WR. Optimizing antiepileptic drug therapy in the elderly. Ann Pharmacother 2005; 39 (11): 1852–60.Google Scholar