When caring for older patients, the changes in physiology and drug metabolism are important to keep in mind and consider in the context of each prescription, as well as comprehensive medication list assessments. These changes include pharmacokinetics (absorption, distribution, metabolism, and excretion); pharmacodynamics (physiologic effects of the mediation), as well as age-related changes in body composition and physiology. Table 13.1 summarizes these changes in older patients.

Even though older patients with multiple comorbidities are frequently the ones being prescribed multiple medications, this group is often underrepresented in the clinical drug trials. There are several reasons for this underrepresentation. Some of these reasons include complex protocols, research focus on aggressive therapies with substantial toxicity, restrictive entry criteria often excluding concurrent conditions and medication, limited expectations of benehts of patients and their families, and lack of hnancial, logistic, and social support [28]. Van Spall et al. published a study looking at exclusion criteria for RCTs done between 1994 and 2006 in general medical journals with a high

TABLE 13.1

Age-Related Physiologic Changes and Potential Pharmacokinetic Consequences

Age-Related Alterations


Body composition

T Body fat l Total body water

T Vd and longer t1/2 for lipophilic medications l Vd, increased plasma concentration of hydrophilic medications

Protein binding

l Serum albumin

T Free fraction of in plasma of highly protein-bound acidic medications

Gastrointestinal function

l GI motility l pH

Potential increased vulnerability to opiate-related bowel dysmotility Rarely clinically significant

Liver function

l Hepatic blood flow

l First-pass effect, resulting in higher medication bioavailability

Kidney function

l Renal blood flow l Glomerular filtration rate (GFR)

l Renal elimination of medications, resulting in prolonged effects of metabolites

Tissue sensitivity

Changes in receptor number, second-messenger function, and cellular response

Potential T or l in sensitivity to an agent

Source: Geller AI et al. PM&R 2012;4(3):198-216.

impact factor [29]. They found that patients were excluded due to age in 72.1% of all trials (38.5% specihcally in older adults). Individuals receiving commonly prescribed medications were excluded in 54.1% of trials. Of all exclusion criteria, only 47.2% were graded as strongly justihed in the context of the specihc RCTs.

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