http://evolve.elsevier.com/McCuistion/pharmacology
By 2033, persons over the age of 65 will outnumber those under the age of 18 in the United States. There are expected to be over 98 million older adults by the year 2060, with close to 20 million over the age of 85. These numbers are staggering, more so considering 92% of older adults have at least one chronic illness, and over 75% of older adults have two chronic illnesses. Typically, persons with two or more chronic conditions take five or more prescription drugs.
Over half of all older adults use at least one over-the-counter (OTC) drug, and nearly three-quarters of older adults use at least one supplement to augment their prescription drugs; however, older adults are more likely to experience adverse reactions or drug interactions related to OTC drugs and supplements, many times resulting in hospitalization.
Administration of drugs in the older adult population requires special attention to age-related factors that influence drug absorption, distribution, metabolism, and excretion. Drug dosages are often adjusted according to the older adult’s weight, laboratory results (e.g., liver enzymes and glomerular filtration), and comorbid health problems. Because of altered organ function in the older adult, the effects of drug therapy must be closely monitored to prevent adverse reactions and possible toxicity.
Drug toxicity may develop in the older adult for drug doses that are within the therapeutic range for the younger adult. These therapeutic drug ranges are usually safe for young and middle-aged adults but are not always within the safe range for older adults. It has been suggested that drugs for older adults should initially be prescribed at low dosages with a gradual increase in dosage based on therapeutic response; this practice is commonly stated as start low and go slow. This approach to drug prescribing reduces the chance of drug toxicity.
Common characteristics in older adults that increase the risk for problems with drug administration include lack of coordinated care, recent discharge from the hospital, self-treatment, multiple diagnoses, sensory and physical changes associated with aging, multiple health care providers, and cognitive impairment.
Physiologic Changes
Physiologic changes associated with aging can influence absorption, distribution, metabolism, and excretion of drugs as well as pharmacodynamic responses at receptors and target organs. These physiologic changes include the following:
• A reduction in total body water and lean body mass, resulting in increased body fat, which alters the volume of distribution of drugs.
• A reduction in kidney mass and lower kidney blood flow, leading to a reduced glomerular filtration rate (GFR) and reduced clearance of drugs excreted by the kidneys.
• A reduction in liver size and blood flow, resulting in reduced hepatic clearance of drugs.
A decline in the physiologic processes that maintain equilibrium in the older adult may mean a higher incidence of adverse effects. Examples of this include:
• Postural hypotension in response to drugs that reduce blood pressure
• Volume depletion and electrolyte imbalance in response to diuretics
• Excessive bleeding with anticoagulant and antiplatelet drugs
• Altered glycemic response to antidiabetic drugs
• Gastrointestinal (GI) irritation with nonsteroidal antiinflammatory drugs (NSAIDs)
Physiologic changes with aging affect the determination of risk versus benefit underlying drug choice, dose, and frequency.
Pharmacokinetics
Pharmacologic processes have not received adequate study in the older adult, therefore a thorough understanding of pharmacokinetics is necessary for the safe administration of drugs in this population.
Absorption
Adults experience several GI changes with aging that may influence drug absorption. These include a decrease in small-bowel surface area, slowed gastric emptying, reduced gastric blood flow, and a 5% to 10% decrease in gastric acid production. These changes are not always clinically relevant; however, calcium carbonate is affected by the decreased gastric acidity. Older adults should be prescribed calcium citrate, which requires a less acidic environment for dissolution. Other common problems that occur in older adults that can significantly influence drug absorption include swallowing difficulties, poor nutrition, and dependence on feeding tubes.
Distribution
Aging can significantly alter drug distribution. With aging, adults experience a decline in muscle mass and a 20% to 40% increase in fat. The increase in body fat means lipid-soluble drugs have a greater volume of distribution, increased drug storage, reduced elimination, and a prolonged period of action. Older adults have a 10% to 15% reduction in total body water, which affects water-soluble drugs, and a 10% reduction in albumin. Reduced albumin levels can result in decreased protein binding of drugs and increased free drug available to exert therapeutic effects, but it also increases the risk for drug toxicity.
Metabolism
Hepatic blood flow in the older adult may be decreased by 40%; aging also results in a 15% to 30% decrease in liver size and a reduction in cytochrome P450 (CYP450) enzyme activity that is responsible for the breakdown of drugs. Drug clearance by hepatic metabolism can be reduced by these age-related changes. A reduction in hepatic metabolism can decrease first-pass metabolism and can prolong drug half-life, resulting in increased drug levels and potential drug toxicity. Nurses must be aware of these metabolic changes and must monitor response to drug therapy to avoid adverse reactions.
To assess liver function, liver enzymes must be checked. Elevated levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) may indicate possible liver dysfunction. However, an older adult can have normal liver function test (LFT) results and still have impaired hepatic enzyme activity.
Excretion
Renal excretion of drugs decreases with age. Excretion is altered by age-related changes in kidney function, such as decreased renal size and volume, which differ for each individual. However, it is generally accepted that the GFR declines by 1 mL/min after the age of 40 (normal GFR is 100 to 125 mL/min). Despite a decline in kidney function, an individual’s creatinine may remain normal as he or she ages due to a decline in muscle mass and activity. Changes in kidney function affect many drugs, leading to a prolonged half-life and elevated drug levels. Changes in kidney function require dosage adjustment, especially if the drug has a narrow therapeutic range.
GFR can be calculated using the Cockroft-Gault formula, which is the formula recommended by the U.S. Food and Drug Administration (FDA) and therefore used by pharmaceutical manufacturers when determining dosage adjustments:
CCr=[(140−age)×weight)/(72×SCr)]×0.85(iffemale)
Abbreviations/Units: CCr (creatinine clearance) = mL/minute; Age = years; Weight = kg; SCr (serum creatinine) = mg/dL.
However, it can also be estimated by many calculators found on the Internet (www.globalrph.com/crcl.htm).
Nurses must have a general understanding of drug classifications that require dosage adjustment in patients with chronic kidney disease (CKD). The mnemonic BANDD CAMP (Table 6.1) may be helpful in remembering the drug classifications; however, nurses should not rely on their memory for drug administration. Package inserts, up-to-date drug reference books, and reputable websites (www.globalrph.com/index_renal.htm) maintain current dosing information.
Pharmacodynamics
Pharmacodynamic responses to drugs are altered with aging as a result of changes in the number of receptor sites, which affects the affinity of certain drugs. These changes are seen most clearly in the cardiovascular and central nervous systems.
Older adults experience a loss of sensitivity in adrenergic receptors, affecting both agonists and antagonists; this results in a reduced response to beta blockers and beta2 agonists. Older adults also experience a blunting in compensatory reflexes leading to orthostatic hypotension and falls.
With age, there is a reduction in dopaminergic and cholinergic receptors, neurons, and available neural connections in the brain. There is reduced blood flow to the brain, and the blood-brain barrier also becomes more permeable. This puts the older adult at risk for central nervous system (CNS) drug side effects, which include dizziness, seizures, confusion, sedation, and extrapyramidal effects.
Nursing Implications: Older Adult Drug Dosing and Monitoring
Polypharmacy
Polypharmacy refers to the use of more medications than is medically necessary. There is little agreement on the actual number of drugs that constitutes polypharmacy, but researchers use five drugs because this number has been associated with increased incidence of adverse drug reactions, geriatric syndromes, and increased mortality.
Risk factors associated with polypharmacy include advanced age, female sex, multiple health care providers, use of herbal therapies and OTC drugs, multiple chronic diseases, and the number of hospitalizations and care transitions. Polypharmacy can cause an increase in geriatric syndromes (cognitive impairment, falls, decreased functional status, urinary incontinence, and poor nutrition) as well as an increased incidence of adverse drug reactions and poor adherence.
Pharmacotherapy in older adults is complex. In order to reduce the risk for and incidence of polypharmacy, nurses must be involved in the coordination of care for older adults. Older adults should be encouraged to use only one pharmacy and should give the pharmacist a list of all the drugs taken—prescribed, herbal, and OTC. A properly informed pharmacist will be able to conduct a clinical review of the patient’s drugs to ensure the appropriateness of therapy. A pharmacist can also confirm patient understanding of individual therapy and can monitor responses to drug therapy. All of this is done to improve the overall quality of life of patients in their care.
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