Essentials of Geriatric Pharmacotherapy
By Holly M. Holmes, M.D.
University of Chicago
A central purpose of geriatrics fellowship training is to learn about the physiology of aging, clinical geriatric syndromes, and strategies to improve function and quality of life in older persons. Geriatric pharmacotherapy is a broad area in which an understanding of the unique susceptibilities of older persons to the risks of medication use is essential. As geriatricians, we can provide better care by prescribing more effectively. This article will review key topics important to understanding the challenges of prescribing for older persons and provide a basic bibliography in geriatric pharmacotherapy.
Polypharmacy
Polypharmacy is a well-recognized problem. A succinct review on suboptimal prescribing in the elderly is provided by Hanlon et al (1). Polypharmacy has many definitions, the most basic of which is numeric, eg., the use of 5 or more medications. This definition is based on a drastic rise in potential drug interactions with the use of 5 or more meds. Other definitions are based on clinical judgment, e.g., the prescribing cascade of using medications to treat the side effects of other medications or prescribing more drugs than clinically indicated. Higher numbers of medications are associated with an increased risk for adverse drug reactions as well as the use of inappropriate medications. Reduction in this risk is important, since up to 30% of older persons experience an adverse drug reaction (ADR) each year. In a meta-analysis of ADRs and hospitalization, ADRs accounted for 6.7% of hospital admissions, and in-hospital ADRs were extrapolated as the 4th to 6th leading cause of in-hospital mortality.(2) Reducing polypharmacy is an important part of addressing preventable adverse drug reactions.
However, polypharmacy is not the only issue; there is substantial evidence to support the under treatment of many chronic conditions in the elderly, like heart failure, hypertension, and atrial fibrillation. 'Polytherapy,' in contrast to polypharmacy, describes the appropriate treatment of multiple comorbidities with multiple medications. In fact, many common conditions affecting older persons are optimally managed by multiple medications; therefore, a strict numbers approach to prescribing is no longer adequate.
Inappropriate Prescribing
In order to improve prescribing in older persons, many investigators have addressed the issue of inappropriate prescribing. A potentially inappropriate medication is one which should be avoided in older persons, or should be avoided in certain doses, disease states, or in combination with other medications in the elderly. Inappropriate medications are prevalent (about 20% of ambulatory elderly persons take an inappropriate drug each year) and lead to increased healthcare utilization and poorer self-rated health. There are many criteria for appropriate prescribing in various settings, generally of two forms: explicit and implicit criteria.
Explicit criteria are lists of medications, dosages, or drug-drug and drug-disease combinations which should be avoided in the elderly. Generally these criteria are derived from the consensus of expert panels based clinical expertise and extensive review of the literature supporting the risk of use of a particular drug in the elderly. Implicit criteria are more general lists of prescribing practices or tests that must be satisfied before a medication can be prescribed.
Two of the most commonly cited and utilized criteria for appropriate prescribing in the elderly are the Beers Criteria and the Medication Appropriateness Index. (3,4) The Beers Criteria was originally developed in 1991 to apply to patients residing in long-term care facilities, but has since been updated twice and includes all patients 65 years and older. The Medication Appropriateness Index is a list of 10 conditions regarding medication use that are widely applicable in prescribing. Shelton, et al. review some of the tools to assess appropriate prescribing in older persons. (5)
Aging Pharmacokinetics and Pharmacodynamics
Pharmacokinetic alterations in older persons are an excellent example of age-related loss of physiologic reserve, resulting in changes with high inter-individual variability. The most important of these changes is the loss of renal function with aging, resulting in decreased clearance of many commonly used drugs. In addition, the loss of lean body mass and later, the loss of fat mass, leads to an altered volume of distribution for many hydrophilic and lipophilic drugs, respectively. Less understood, and likely with more individual variation, is the decrease in hepatic cytochrome P-450 enzyme activity, altering the metabolism of many drugs. Pharmacodynamic effects, the clinical actions of drugs that depend on receptor interactions and regulatory mechanisms, may also be altered with aging. A common example is the increased orthostatic response to antihypertensives due to altered baroreceptor responsiveness. (6)
Pharmacogenetics
Finally, pharmacogenetics has an enormous potential impact in geriatrics, in anticipating drug efficacy, increased susceptibility to adverse drug reactions or interactions, and even in genetically tailoring therapies. In the future, this may be a tool by which clinicians can detect genetic polymorphisms that, in addition to age-related changes in pharmacokinetics, alter drug response. (7)
In summary, prescribing medications for older persons is a dangerous task which challenges geriatricians in every patient encounter. A basic understanding of concepts in aging pharmacotherapy will help geriatricians approach medication use with the proper amount of caution. Prescribing the right drug at the right dose for the appropriate patient is one the most important tasks we do as physicians.
The following references are key readings in geriatric pharmacotherapy.
1. Hanlon JT, Schmader KE, Ruby CM, Weinberger M. Suboptimal prescribing in older inpatients and outpatients. JAGS 2001; 49: 200-209.
2. Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA 1998; 279:1200-1205.
3. Fick DM, Cooper JW, Wade WE, et al. Updating the Beers criteria for potentially inappropriate medication use in older adults. Arch Intern Med 2003; 163: 2716-2724.
4. Hanlon JT, Schmader KE, Samsa GP, et al. A method for assessing drug therapy appropriateness. J Clin Epidemiol 1992; 45: 1045-1051.
5. Shelton PS, Fritsch MA, Scott MA. Assessing medication appropriateness in the elderly: a review of available measures. Drugs & Aging 2000; 16: 437-450.
6. Mangoni AA, Jackson SHD. Age-related changes in pharmacokinetics and pharmacodynamics: basic principles and practical applications. Br J Clin Pharmacol 2003; 57: 6-14.
7. David SP. Pharmacogenetics. Prim Care Clin Office Pract 2004; 31: 534-559.
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