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Responsiveness to Drugs at Extremes of Age

  • K. O’Malley
  • J. G. Kelly

Abstract

In general, responsiveness to drugs depends on a combination of pharmacokinetic and pharmacodynamic factors. The pharmacokinetic factors are those which govern the absorption of drugs, transport to their sites of action, distribution to various tissues, metabolism and elimination. The pharmacodynamic factors are those which govern the type, intensity and duration of action of drugs. Studies on drug responses at extremes of age must examine both sets of factors. Increased central effects of a drug could be due to either increased penetration into the central nervous system or to altered tissue response. Pharmacokinetic processes are of course easier to study particularly with the advent of increasingly sensitive and specific methods of measuring drugs and their metabolites in biological fluids. These studies are also easier in adult subjects since it is of course easier to obtain repeated adequate blood samples. As a result there is a relative abundance of pharmacokinetic studies in the elderly. However, even in infants and children increasingly complex pharmacokinetic studies can be attempted as more sophisticated methodology allows the use of small samples of blood.

Keywords

Adverse Drug Reaction Spinal Anaesthesia Drug Response Boston Collaborative Drug Surveillance Program Pharmacodynamic Factor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Berger, M., Preiss, H., Hesse-Wortman, C. & Gries, F. A. (1971). Norepinephrine-lipolysis in isolated fat cells of non-obese aged humans (72 yr). Gerontol., 17, 312–322.CrossRefGoogle Scholar
  2. Berman, P. H. (1976). Management of seizure disorders with anticonvulsant drugs. Current concepts. Ped. Clin. N. Am., 23, 443–459.Google Scholar
  3. Bertel, O., Buhler, F. R., Kiowski, W. & Lutold, B. E. (1980). Decreased beta adrenoceptor responsiveness as related to age, blood pressure and plasma catecholamines in patients with essential hypertension. Hypertension, 2, 130–138.CrossRefPubMedGoogle Scholar
  4. Bitenskyu, M. W., Russell, V. & Blanco, M. (1970). Independent variation of glucagon and epinephrine responsive components of hepatic adenyl cyclase as a function of age, sex and steroid hormones. Endocrinology, 86, 154–159.CrossRefGoogle Scholar
  5. Boston Collaborative Drug Surveillance Program. (1972). Drug Surveillance: Problems and Challenges. Ped. Clin. N. Am., 19, 117–129.Google Scholar
  6. Bylund, D. M., Tellez-Inon, M. T. & Hollenberg, M. D. (1977). Age-related parallel decline in beta-adrenergic receptors, adenylate cyclase and phosphodiesterase activity in rat erythrocyte membranes. Life Sci., 21, 403–410.CrossRefPubMedGoogle Scholar
  7. Camfield, C. S., Chaplin, S., Doyle, A. B., Shapiro, S. H., Cummings, C. & Camfield, P. R. (1979). Side effects of phenobarbital in toddlers: behavioral and congenitive aspects. J. Pediat., 95, 361–365.CrossRefPubMedGoogle Scholar
  8. Caranasos, G. J., Stewart, R. B. & Guff, L. E. (1974). Drug induced illness leading to hospitalization. J. Am. med. Ass., 228, 713–717.CrossRefGoogle Scholar
  9. Castleden, C. M., George, C. F., Marcer, D. & Hallett, C. (1977). Increased sensitivity to nitrazepam in old age. Brit. med. J., 1, 10–12.PubMedCentralCrossRefPubMedGoogle Scholar
  10. Chan, K., Kendall, M. J., Mitchard, M., Wells, W. D. E. & Vickers, M. D. (1975). The effect of ageing on plasma pethidine concentration. Brit. J. clin. Pharmac., 2, 297–302.CrossRefGoogle Scholar
  11. Cusack, B., Kelly, J. G., O’Malley, K, Noel, J., Lavan, J. & Horgan, J. (1979). Digoxin in the elderly: Pharmacokinetic consequences of old age. Clin. Pharmac. Ther., 25, 772–776.Google Scholar
  12. Dillon, N., Chung, S., Kelly, J. & O’Malley, K. (1980). Age and beta adrenoceptor-mediated function. Clin. Pharmac. Ther., 27, 769–772.CrossRefGoogle Scholar
  13. Dohi, S., Naito, H. & Takahasi, T. (1979). Age-related changes in blood pressure and duration of motor block in spinal anaesthesia. Anaesthesiol, 50, 319–323.CrossRefGoogle Scholar
  14. Erdmann, E. & Hasse, W. (1973). Quantitative aspects of ouabain binding to human erythrocyte and cardiac membranes. J. Physiol, 251, 671–682.CrossRefGoogle Scholar
  15. Fleish, J. H., Maling, H. M. & Brodie, B. B. (1970). Beta receptor activity in aorta: variations with age and species. Circulation Res., 26, 151–162.CrossRefGoogle Scholar
  16. Gorodischer, R., Jusko, W. J. & Yaffe, S. J. (1976). Tissue and erythrocyte distribution of digoxin in infants. Clin. Pharmac. Ther., 19, 256–263.Google Scholar
  17. Greenberg, L. H. & Weiss, B. (1979). Ability of aged rats to alter beta adrenergic receptors of brain in response to repeated administration of reserpine and desmethylimipramine. J. Pharmac. exp. Ther., 211, 309–316.Google Scholar
  18. Hewick, D. S. & Shaw, V. (1978). Tissue distribution of radioactivity after injection of 14C nitrazepam in young and old rats. J. Pharm. Pharmac., 30, 318–319.CrossRefGoogle Scholar
  19. Hurwitz, N. (1969). Admissions to hospital due to drugs. Brit. med. J., 1, 539–540.PubMedCentralCrossRefPubMedGoogle Scholar
  20. Kearin, M., Kelly, J. G. & O’Malley, K. (1980). Altered digoxin ‘receptors’ in neonates: an explanation of decreased sensitivity to digoxin? Clin. Pharmac. Ther., in press.Google Scholar
  21. Klein, U., Klein, M., Sturm, H., Rothenbuhler, M., Huber, R., Stucki, P., Gikalov, I., Keller, M. & Hoigne, R. (1976). The frequency of adverse drug reactions as dependent upon age, sex and duration of hospitalization. Int. J. clin. Pharmac., 13, 187–195.Google Scholar
  22. Koch-Weser, J. (1973). Correlation of pathophysiology and pharmacotherapy in primary hypertension. Am. J. Cardiol, 32, 499–510.CrossRefPubMedGoogle Scholar
  23. Lakatta, E. G., Gerstenblith, G., Angeli, C. S., Shock, N. W. & Weisfeldt, M. L. (1975). Diminished inotropic response of aged myocardium to catecholamines. Circulation Res., 36, 262–269.CrossRefPubMedGoogle Scholar
  24. Lipton, L., Steinschneider, A. & Richmond, J. B. (1965). The autonomic nervous system in early life. New Eng. J. Med, 273, 147–153 and 201–208.CrossRefPubMedGoogle Scholar
  25. McKenzie, M. W., Marchall, G. L., Netzloff, M. L. & Cluff, L. E. (1976). Adverse drug reactions leading to hospitalization in children. J. Paediat., 89, 487–490.CrossRefGoogle Scholar
  26. Nugent, S. K., Laravuso, R. & Rogers, M. C. (1979). Pharmacology and use of muscle relaxants in infants and children. J. Paediat., 94, 481–487.CrossRefGoogle Scholar
  27. O’Malley, K. & O’Brien, E. (1980). Management of hypertension in the elderly. New Eng. J. Med, 302, 1397–1401.CrossRefPubMedGoogle Scholar
  28. O’Malley, K., Stevenson, I. H., Ward, C. A., Wood, A. I. & Crooks, J. (1977). Determinants of anticoagulant control in patients receiving warfarin. Brit. J. clin. Pharmac., 4, 309–314.CrossRefGoogle Scholar
  29. Rezvani, I. & Di George, A. M. (1977). Reassessment of the daily dose of oral thyroxine for replacement therapy in hypothyroid children. J. Paediat., 90, 291–297.CrossRefGoogle Scholar
  30. Seidl, L. G., Thornton, G F., Smith, J. W. & Cluff, L. F. (1966). Studies on the epidemiology of adverse drug reactions. Bull. Johns Hopkins Hosp., 119, 299–315.Google Scholar
  31. Shepherd, A. M. M., Hewick, D. S., Moreland, T. A. & Stevenson, I. H. (1977). Age as a determinant of sensitivity to warfarin. Brit. J. clin. Pharmac., 4, 315–320.CrossRefGoogle Scholar
  32. Shocken, D. & Roth, G (1977). Reduced beta adrenergic receptor concentrations in ageing man. Nature, 267, 856–857.CrossRefGoogle Scholar
  33. Simon, A. C., Safar, M. A., Levenson, J. A., Kheder, A. M. & Levy, B. I. (1979). Systolic hypertension: haemodynamic mechanism and choice of anti-hypertensive treatment. Am. J. Cardiol, 44, 505–511.CrossRefPubMedGoogle Scholar
  34. Tuttle, R. S. (1966). Age related changes in the sensitivity of rat aortic strips to norepinephrine and associated chemical and structural alterations. J. Gerontol, 21, 510–516.CrossRefPubMedGoogle Scholar
  35. Vestal, R. E., Wood, A. J. J. & Shand, D. G (1979). Reduced γ-adrenoceptor sensitivity in the elderly. Clin. Pharmac. Ther, 26, 181–186.Google Scholar

Copyright information

© The contributors 1980

Authors and Affiliations

  • K. O’Malley
    • 1
  • J. G. Kelly
    • 1
  1. 1.Department of Clinical PharmacologyRoyal College of Surgeons in IrelandSt. Stephen’s GreenEire

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