Never before have doctors had such an abundance of therapeutic options. And—not surprisingly—elderly patients are taking more medications than ever.
A national survey from 1998 revealed that more than 40% of elderly American adults take five or more medications a day—and that’s at home. Meantime, drug-related complications have risen steadily.
In 2005, the United States spent $177 billion in the management of drug-related problems—$34 billion more than was spent on the drugs themselves.1 Because up to a third of adverse medication effects warrant a hospital admission, hospitalists are the front line in the diagnosis and treatment of these syndromes.
Additionally, medication-related consequences can complicate hospitalizations required for other reasons. They can be observed as frequently as weekly according to hospitalist Balazs Zsenits, MD, FACP, of Rochester (N.Y.) General Hospital—and they’re often serious. In fact, medication reactions are so frequently fatal they represent the fifth-leading cause of death in the United States.
As one might expect, the elderly are disproportionately affected by the potentially toxic consequences of medication. In fact, a 2005 study published in Pharmacotherapy revealed that more than two-thirds of hospitalized elderly adults had an adverse drug effect over a four-year period.2 Among the more common outcomes were constipation, falls, immobility, confusion, hip fractures, and a decline in functional status requiring nursing home placement. Moreover, the authors noted that drug side effects frequently mimicked other geriatric syndromes, prompting physicians to prescribe additional medication.
While multiple medications may be necessary to prevent the progression of disease in older people, the overuse and misuse of drugs has been linked to serious health problems, including hospitalizations and death.
Patients at greatest risk for a polypharmacy-associated medical complication are those taking five or more concurrent drugs, those with multiple physicians, patients with significant medical comorbidities or impairments in vision or dexterity, and individuals who have recently been hospitalized.4-5 At least 25% of elderly Americans fall into at least one of these categories
But polypharmacy is not the only reason elderly patients experience a disproportionately high rate of adverse medication effects. Age-related altered drug metabolism is also responsible for unexpected drug consequences in this age group.
Aging influences every aspect of physiologic drug processing. While the absorption of oral medications from the GI tract remains relatively constant in the absence of disease states and gastric pH altering medications, bioavailability and clearance dramatically change with aging. These changes become the most pronounced after age 75, when kidney and liver function become limited.
As people age, their total body water decreases, their lean body mass is reduced, and their percentage of body fat increases. This increase in body fat expands the volume of distribution for lipophilic drugs and also decreases the volume of distribution for hydrophilic drugs.6 The result is that water-soluble medications have an elevated active serum concentration, and lipid-soluble agents, while they may have a decreased serum concentration, have a prolonged half-life.
These effects are best exemplified by examining what happens after a geriatric patient takes diazepam. A lipid-soluble drug, diazepam and its metabolites will be stored in an increasingly large body compartment. This will temporarily decrease the serum level of the drug, but will prolong the half-life from an average of 20 hours to greater than 50 hours. Repeated dosing will quickly result in toxic serum levels, at which point the patient is at risk for CNS side effects as well as falls and fractures.
The aging process also affects the role of drug-binding serum proteins. The total serum protein level is usually maintained (while albumin levels may diminish slightly, increasing levels of alpha 1 antitrypsin keeps the total protein level normal). More significantly, the affinity of the serum proteins for protein-bound drugs lessens as patients age. The degree of plasma protein binding has a significant impact on the pharmacologic activity of the drug, because it is the free drug that is physiologically active and exerts the pharmacologic effect.