Pharmacodynamics in Older Adults: A Review

https://doi.org/10.1016/j.amjopharm.2007.10.001Get rights and content

Abstract

Background: Older individuals experience physiologic changes in organ function related to aging or to specific disease processes. These changes can affect drug pharmacodynamics in older adults.

Objective: The goal of this article was to review age-related changes in pharmacodynamics and their clinical relevance.

Methods: PubMed and International Pharmaceutical Abstracts were searched (January 1980-June 2006) for the following combination of terms: pharmacodynamic and elderly, geriatric or aged. References cited in other reviews were also evaluated. The current review focused on age-related pharmacodynamic changes in agents affecting the central nervous system (CNS), cardiovascular, and endocrine functions.

Results: Older adults frequently demonstrate an exaggerated response to CNS-active drugs. This is in part due to an underlying age-related decline in CNS function and in part due to increased pharmacodynamic sensitivity for some benzodiazepines, anesthetics, and opioids. The most important pharmacodynamic differences with age for cardiovascular agents are the decrease in effect for J3-adrenergic agents. This decline in response in vascular, cardiac, and pulmonary tissue may be due to a decrease in Gs protein interactions. Most studies indicate there is no decrease in cx-receptor sensitivity with age. Angiotensin-converting enzyme inhibitors do not show age-related differences in elderly patients. With the dihydropyridine calcium channel blockers, there was a slight increase in effect for older adults, but this was only for treatment-naive patients and was transient. Nondihydropyridines did not show an age- associated change in pharmacodynamic effect; however, in the elderly, there appeared to be a decrease in the PR interval prolongation normally seen with these agents. Studies of diuretics indicated that the changes in diuretic and natriuretic effects seen in the elderly were associated with pharmacokinetic changes and were not pharmacody- namic in nature. There was a lack of consistent evidence regarding whether sulfonylureas show age-related changes in pharmacodynamic effect.

Conclusions: There is a general trend of greater pharmacodynamic sensitivity in the elderly; however, this is not universal, and these age-related changes must be investigated agent-by-agent until further research yields greater understanding of the molecular mechanisms underlying the aging process.

References (157)

  • JW Constantine et al.

    Effects of trimazosin and prazosin on blood pressure and on pressor responses to phenylephrine in rats

    Am HeartJ

    (1983)
  • OE Brodde et al.

    Age- dependent decrease of alpha 2-adrenergic receptor number in human platelets

    Eur J PharmacoL

    (1982)
  • AJ McLean et al.

    Aging biology and geriatric clinical pharmacology

    Pharmacol Rev

    (2004)
  • U Klotz

    Effect of age on pharmacokinetics and pharmacodynamics in man

    IntJ Clin Pharmacol Ther

    (1998)
  • A Hammerlein et al.

    Pharmacokinetic and pharmacodynamic changes in the elderly.Clinical implications

    Clin Pharmacokinet

    (1998)
  • SH Jackson

    Pharmacodynamics in the elderly

    J R Soc Med

    (1994)
  • DG Burton et al.

    Bridging the gap: Ageing, pharmacokinetics and pharmacodynamics

    J Pharm Pharmacol

    (2005)
  • SL Sharer

    The pharmacology of anesthetic drugs in el- derly patients

    Anesthesiol Clin North Am

    (2000)
  • AA Mangoni et al.

    Age-related changes in pharmacokinetics and pharmacodynamics: Basic principles and practical applications

    BrJ Clin Pharmacol

    (2003)
  • BR Williams et al.

    Cardiovascular drug therapy in the elderly: Theoretical and practical considerations

    Drugs Aging

    (2003)
  • JG Papp

    Cardiac responses to drugs at the extremes of age

    Therapie

    (1991)
  • KJ Collins

    Age-related changes in autonomic control: The use of beta blockers in the treatment of hypertension

    Cardiovasc Drugs Ther

    (1990)
  • MC Rodriguez-Julbe et al.

    Antibiotics in older adults

    P R Health SciJ

    (2004)
  • R Peters

    Ageing and the brain

    Postgrad Meal J

    (2006)
  • R Toornvliet et al.

    Effect of age on functional P-glycoprotein in the blood-brain barrier measured by use of (R)-[(ll)C]verapamil and positron emission tomography

    Clin Pharmacol Ther

    (2006)
  • LA Tupler et al.

    Alcohol pharmacodynamics in young-clderly adults contrasted with young and middle-aged subjects

    Psychopharmacology (Berl)

    (1995)
  • JC Fleishaker et al.

    Pharmacokinetics and pharmacodynamics of adinazolam and N-desmethyladinazolam after oral and intrave- nous dosing in healthy young and elderly volunteers

    J Clin Psychopharmacol

    (1992)
  • PD Kroboth et al.

    Alprazolam in the elderly: Pharmacokinetics and pharmacodynamics during multiple dosing

    Psychopharmacology (Berl)

    (1990)
  • RB Smith et al.

    Influence of dosing regimen on alprazolam and metabolite serum concentrations and tolerance to sedative and psychomotor effects

    Psychopharmacology (Berl)

    (1987)
  • GB Kaplan et al.

    Singledose pharmacokinetics and pharmacodynamics of alprazolam in elderly and young subjects

    J Clin Pharmacol

    (1998)
  • CG Swift et al.

    Single dose pharmacokinetics and pharmacodynamics of oral loprazolam in the elderly

    Br J Clin Pharmacol

    (1985)
  • S Albrecht et al.

    The effect of age on the pharmacokinetics and pharmacodynamics of midazolam

    Clin Pharmacol Ther

    (1999)
  • JR Jacobs et al.

    Aging increases pharmacodynamic sensitivity to the hypnotic effects of midazolam

    Anesth Analg

    (1995)
  • HP Platten et al.

    Pharmacokinetics and the pharmacodynamic action of midazolam in young and elderly patients undergoing tooth extraction

    Clin Pharmacol Ther

    (1998)
  • J Sonne et al.

    Single dose pharmacokinetics and pharmacodynamics of oral oxazepam in very elderly institntionalised subjects

    Br J Clin Pharmacol

    (1991)
  • DJ Greenblatt et al.

    Age and gender effects on the pharmacokinetics and pharmacodynamics of triazolam, a cytochrome P450 3A sub- strate

    Clin Pharmacol Ther

    (2004)
  • DJ Greenblatt et al.

    Sensitivity to triazolam in the elderly

    NEnglJMed

    (1991)
  • DW Robin et al.

    Increased baseline sway contributes to increased losses of balance in older people following triazolam

    JAm Geriatr Soc

    (1996)
  • WA Ray et al.

    Benzodiazepines of long and short elimination half-life and the risk of hip fracture

    JAMA

    (1989)
  • WA Ray et al.

    Benzodiazepines and the risk of falls in nursing home residents

    JAm Geriatr Soc

    (2000)
  • RG Cumming et al.

    Benzodiazepines and risk of hip fractures in older people: A review of the evidence

    CNS Drugs

    (2003)
  • DJ Greenblatt et al.

    Effect of age, gender, and obesity on midazolam kinetics

    Anesthesiology

    (1984)
  • F Servin et al.

    Pharmacokinetics ofmidazolam used as an intravenous induction agent lfbr patients over 80 years of age

    Eur J Anaesthesiol

    (1987)
  • J Kanto et al.

    Effect of age on the pharmacokinetics and sedative effects of flunitrazepam

    Int J Clin Pharmacol Ther Toxicol

    (1981)
  • N Pomara et al.

    The acute and chronic perl~brmance effects of alprazolam and loraze pam in the elderly: Relationship to duration of treatment and self-rated sedation

    Psyehopharmacol Bull

    (1998)
  • PC Bickfbrd et al.

    Benzodiazepine modulation of GABAergic responses is intact in the cerebellum of aged F344 rats

    Neurosci Lett

    (2000)
  • I Sundman et al.

    GABA uptake sites in frontal cortex from suicide victims and in aging

    Neuropsyehobiology

    (1997)
  • JR Arden et al.

    Increased sensitivity to etomidate in the elderly: Initial distribution versus altered brain response

    Anesthesiology

    (1986)
  • TW Schnider et al.

    The influence of age on propofbl pharmacodynamics

    Anesthesiology

    (1999)
  • T Kazama et al.

    Optimal propofbl plasma concentration during upper gastrointestinal endoscopy in young, middle-aged, and elderly patients

    Anesthesiology

    (2000)
  • Cited by (185)

    View all citing articles on Scopus
    View full text