Americans are aging at an unprecedented rate. Currently, the proportion of the population that is 65 years and older exceeds 12%, or about 40 million.1 It is projected that this population will grow significantly between the years 2010 and 2050, particularly the 65 and older group, which will more than double. This is largely due to the aging of the Baby Boomer generation who began turning 65 in January 2011. Age and chronic conditions are associated with increased use of healthcare.2 Nurse practitioners in adult and family practice will see a larger proportion of older patients who present a complex and potentially high-risk group that will require medications.
Prescribing safely and effectively for the older adult is contingent upon understanding the age-related changes that affect the pharmacodynamics and pharmacokinetics of drugs. Evidence-based guidance is limited as there are few clinical trials that contain significant numbers of subjects over the age of 65. In fact, most clinical drug trials that include older adults limit inclusion to the age range of 65 to 74; few include subjects over the age of 75.3-5 The prescriber must consider the effects of polypharmacy that put elderly patients at risk for adverse drug events (ADEs), iatrogenesis, and drug interactions, as well as the issues of adherence and cost. This article will discuss the effect of aging systems on the pharmacokinetics and dynamics of drugs, common problems that put the older patient at risk for ADE, strategies to improve adherence, and models that guide the practitioner to safely and effectively prescribe for the elderly.
Normal changes in physiologic processes as well the as the effects of acute and chronic conditions may significantly change the way a drug is absorbed, distributed, metabolized, and eliminated in the aging patient. It is imperative that the prescriber consider these possible alterations in pharmacokinetics when treating a patient with medications to avoid iatrogenesis and ADE.6
Pharmacokinetics
Absorption. The effects of normal aging on the passive absorption of drugs are not clear. Decreased acidity and function of mucosal cells in the stomach may affect the absorption of some drugs that require an acidic environment (such as vitamin B12). Altered motility through the gastrointestinal (GI) tract and decreased blood flow to the bowel may all affect the absorption of oral medications, but the GI tract has such a large surface area that these effects are minimal.4,7 More often, it is concurrent therapy, such as antacids that create an alkaline environment, and anticholinergics that may contribute to decreased motility and interfere with the active transport of drugs into the body.
Absorption of topical medications can be affected by decreased hydration, tissue thickness, and surface lipids on the skin.7 Transdermal medications are designed for gradual absorption and rely on intact, well hydrated, healthy skin with adequate circulation. Applying topical medications to nonintact skin can greatly increase the rate of absorption, while dry, thin skin without a good subcutaneous layer can inhibit absorption of the drug. Suboptimal placement of transdermal medications can lead to an over- or undertreatment effect.
Distribution. In the older adult, drug distribution is affected by a number of age-related changes including a decrease in total body water and serum albumin while body fat increases. Drugs that are water-soluble (such as digoxin, theophylline) are distributed in a smaller area, and this may lead to toxicity at the same dose that would be prescribed for a younger or middle-aged adult. Similarly, drugs that are fat-soluble may accumulate in body fat, prolonging the effect and resulting in ADE. This is especially hazardous with medications that affect the central nervous system (CNS), such as benzodiazepines.
Low serum albumin, a common finding in older adults, has the most significant effect on the distribution of medications. Many drugs are highly protein bound, and serum albumin is the principle plasma protein to which they bind. As less drug is bound to serum proteins, more active drug is circulating freely in the serum competing for binding sites. Toxicity can quickly develop with drugs such as phenytoin, digoxin, and warfarin, putting the patient at risk for ADE. Up to 20% of hospital admissions for patients 65 years and older are related to the effects of medications.7,8
Metabolism. Most drugs are metabolized in the liver. With normal aging, the liver decreases in mass but also in circulation.5,7-10 Decreased blood flow is associated with decreased first pass metabolism, so more drug is available in the bloodstream. This is the main reason that the elderly are prescribed a lower starting dose than the average adult. It is important to be aware of drugs expected to have a high rate of extraction upon first pass through the liver. Lidocaine, meperidine, morphine, propranolol, metoprolol, verapamil, nitrates, and barbiturates (such as phenobarbital) are among the drugs with an elevated first pass effect.3,7,8 These medications, when prescribed at the usual starting dose, may cause significant ADE in an older adult with less vigorous hepatic circulation and resultant decreased first pass effect.
Elimination. Most drugs are eliminated through the renal system. The literature reveals a significant variability of functional limitation in the kidney as a result of normal aging. Structural and biophysiologic changes include a decrease in the number of nephrons, bloodflow, and glomerular filtration rate (GFR).3-5, 7-11 Creatinine clearance has often been used to measure renal function. Creatinine is a byproduct of muscle tissue that is removed by the kidneys, making it an important measure of renal function. However, with normal aging comes a marked decrease in lean muscle mass (sarcopenia), so older adults produce very little creatinine.5,7-10 Sarcopenia contributes to a reduced renal clearance of many drugs (such as digoxin, H2-receptor blockers, fluoroquinolones, penicillins, and aminoglycosides). It is best to consider the GFR, the accepted standard for measuring kidney function, when choosing both a drug and dose for renally impaired clients.
Pharmacodynamics
While pharmacokinetics considers how a drug is taken in, processed, and eliminated from the body, pharmacodynamics is the effect the drug has on the body itself.4,7,11 There are structural and physiologic changes in aging organ systems that can significantly influence the intended treatment effect. Reduced homeostatic responses, reduced tissue receptors, and changes in target organ sensitivity can influence drug effect.
Central nervous system
A number of dynamic changes in the function and sensitivity of neuroreceptors occurs as a result of normal aging, and this can have a significant clinical effect on medication therapy. There are a decreased number of neurons, a decreased cerebral blood flow, and an increase in the permeability of the blood-brain barrier, which exposes the patient to increased sensitivity to the therapeutic and toxic effects of drugs. Medications such as opioids, benzodiazepines, barbiturates, and drugs with anticholinergic activity (such as diphenhydramine, clonidine) can result in cognitive impairment, behavioral changes, and even delirium. Decreased action of dopamine-1 and dopamine-2 receptors can produce extrapyramidal adverse reactions such as extreme restlessness and abnormal involuntary movements with the concomitant use of an antipsychotic and metoclopramide, an anitemetic.8,10
Cardiovascular system
Changes in the cardiovascular system can produce increased sensitivity, but few are reported to do so. However, decreased function of beta-adrenergic receptors can actually require increased amounts of certain drugs to reach desired therapeutic effect, such as isoproterenol and beta-blockers.7,13,16 Baroreceptor function is impaired with aging and manifests clinically as a decreased ability to achieve homeostasis through increased heart rate or vascular tone in the presence of low volume or position change. This has implications in the development of orthostatic hypotension, which puts the older patient at risk for falls and can be exacerbated with antihypertensive medications or diuretics.
Other systemic changes
Impaired glucose regulation can put the older patient at risk for hypoglycemia when antidiabetic medications are prescribed. The prescriber should consider the possibility of an atypical presentation of hypoglycemia when presented with an older patient who exhibits somnolence or confusion in the presence of an antidiabetic medication.7,8
Common problems that put elders at risk
Chronic conditions are common in an aging patient population, and there are often several comorbidities that require medication management. Polypharmacy, defined as the use of two or more medications, is frequent in the elderly population, particularly those residing in long-term-care (LTC) facilities. Older adults have a medication use rate that is three to four times higher than younger adults.18 About 20% of community-dwelling elders are taking 10 or more medications; LTC facility residents represent an even larger percentage of polypharmacy due to increased morbidity.18 This number of medications can be easily reached if practice guidelines are followed for each chronic condition present.15 Evidence shows that clinical practice guidelines do not provide for appropriate and quality care in the older adult with multiple comorbidities.6,11,15,16 These guidelines are designed for single conditions and do not consider the complexity of caring for a patient with several chronic diseases.
Patients are often referred to specialty providers who prescribe concurrently with the primary care provider. Many patients do not communicate clearly with each provider; they may forget some of their medications or fail to mention over-the-counter, herbal, or dietary supplements they may be taking. Confusion over the generic versus brand name of drugs can cause elderly patients to take the same medication in two different forms, increasing the risk of ADE. The fact that older adults tend to have several chronic conditions and, in turn, are prescribed more medications automatically sets them up for potential interactions and ADE. Often, when an older patient is prescribed a medication, adverse reactions from the initial drug lead to the addition of other drugs to combat the undesirable effects leading to what is referred to as the "prescribing cascade."13,15,17,18
Functional limitations
The older patient may have difficulty with adherence to a medication regimen for a variety of reasons. Cognitive impairment can put a patient at risk for either under- or overtreatment. Patients may not adhere if the medication schedule is too complicated, they do not understand the importance of completing the course of a prescription, or if medications have similar sounding names.8,13 Decreased visual acuity can make identification of medications difficult and increase the likelihood of error in administration. Mobility can limit the older person's ability to manage their medications in both procurement and administration. The older patient may have barriers to transportation, being dependent on others for appointments and shopping, and may not be able to fill a prescription in a timely manner. Arthritis or movement disorders such as Parkinson's disease can significantly impair the older adult's fine motor skills, limiting the ability to open the medication containers, handle small pills, or administer insulin.
Cost
Cost is often a significant factor; up to 15% of older adults cannot afford their medications,7 don't fill prescriptions, or may take fewer doses than what is prescribed. Medications that are no longer used may be kept to avoid waste and then used after their effectiveness has been significantly reduced. The elderly may share medications in an effort to avoid a costly trip into the clinic. A common practice to reduce cost is pill splitting, either by the patient or pharmacy. Although this can significantly ease the burden of medication costs, not all medications are safe to split. Checking the manufacturer's prescribing information on the appropriateness of pill splitting is the safest practice.17
High-risk medications
Older adults demonstrate important differences in the way their bodies handle medications and the effects those medications have on their bodies. The Beers Criteria,19 which was published as original research in 1991, updated in 1997,20 and revised in 2002,16 identified a number of drugs that were potentially inappropriate for the elderly. These drugs were determined to have a risk for ADE that outweighed the potential therapeutic effect.15,16,18 In fact, two drugs which appeared on the original list are now off formulary including propoxyphene, which was found to have little analgesic advantage over acetaminophen with far greater risk of ADE and meperidine, which has a high propensity for confusion.16 This criterion has been used to evaluate care in LTC facilities, reduce the potential for ADE in older adults, and as a method for evaluating prescribing patterns for this population.14,15,16,18 While not all of these medications will be discussed here, the more common and potentially dangerous drugs are addressed.
Anticoagulants are commonly prescribed and are drugs with the potential for the most serious consequences. Warfarin should be prescribed carefully, keeping the patient's dose at the lowest possible amount to achieve anticoagulation. As this drug is highly protein bound, it is imperative that the prescriber monitor the serum total protein or albumin as well as the prothrombin time and international normalized ratio. Warfarin is metabolized in the liver, primarily through the CYP2C9 pathway.7 This pathway is used by a large number of other medications and concurrent use greatly increases the possibility of over-anticoagulation. Most notably are most antibiotics, antifungals, nonsteroidal anti-inflammatory drugs (NSAIDs), selective serotonin reuptake inhibitors, and many dietary or herbal supplements. If warfarin is necessary, use this medication at the lowest dose possible for the shortest duration that is feasible, and educate patients to tell any prescriber about their warfarin therapy prior to accepting any new or change in current medications.
Medications with anticholinergic effects can cause dry mouth, skin, and eyes, along with urinary retention and constipation. Of these adverse reactions, urinary retention and constipation are among the most problematic for the older patient. Additionally, age-related changes in the CNS can also predispose the older adult to excess sedation and falls, increased confusion, and delirium with psychosis. The older patient with cognitive impairment of any severity can be at high risk for psychosis with visual or auditory hallucinations. It is important to note the presence of any existing medication with anticholinergic effects before prescribing another anticholinergic drug. These effects are cumulative, and if more than one drug is being used, it exponentially raises the risk. Some commonly used medications with anticholinergic properties include antihistamines (chlorpheniramine, diphenhydramine), antidepressants (especially tricyclics such as amitriptyline and nortriptyline), anti-parkinsonians (amantadine, benztropine), antidiarrheals, and antipsychotics.7,8,9 Antihistamines are not necessarily readily apparent to the consumer when a combination drug is taken. For instance, a popular bedtime medication, Tylenol PM, contains diphenhydramine, which produces drowsiness.
Older patients are more sensitive to the effects of opioid pain medications. Sedation, anorexia, confusion, and constipation can become major problems when treating pain in the elderly. The American Geriatrics Society recommends beginning with scheduled acetaminophen for mild to moderate pain and then progressing to the lowest potency opioid if that method is ineffective.9,13,18 NSAIDs are an option for unrelieved pain with acetaminophen, but the older adult is more likely to suffer from GI inflammation and bleeding7,9 particularly if that patient has gastroesophageal reflux disease, peptic ulcer disease, or concurrent warfarin therapy (seeCommon conditions and associated high-risk medications).
Improving adherence
Prescriptions that remain unfilled or taken incorrectly can also result in harm to the older patient. Initially, the best strategy to improve adherence is to have a complete list of current medications, including prescription, over-the-counter, dietary, and herbal supplements. Instruct the patient to bring in all of those items at the next appointment time, that is, "the brown bag test."4,8,9,10 It is during that appointment that an assessment of the patient's health literacy can be made. The patient should be able to tell the provider which medication is taken for what condition, the appropriate administration route and time, expected therapeutic effects, and adverse reactions that should be reported.
When it is necessary to change a medication regimen or prescribe a new drug, consider first if the new drug is absolutely necessary. Provide verbal and written instructions, not limited to the name of the drug and how often it should be taken, but also how it is expected to benefit the patient, and when to report back to the prescriber if adverse reactions are experienced. Consider the cost, explore generic or less costly alternatives, and discuss the benefits and risks of adding a new drug with the patient and family. Chose a medication that is compatible with other medications currently taken, existing chronic conditions, and with the simplest administration schedule. Once or twice daily medications will increase the likelihood that the patient will adhere to the regimen. Follow up with an appointment sooner than would be expected with younger adults-the elderly tend to be more sensitive to medication effects and more likely to experience adverse reactions.4,6,7,9,17
Models for safe and effective prescribing
The axiom in geriatric prescribing has long been "start low, go slow." Another simple adage, "add one-take one away," can also be helpful. In addition, the American Medical Directors Association has developed guidelines for prescribing decisions for the older adult. This was based on the Beers Criteria20 but it is important to note that these criteria should be used as a guide, within a patient-centered, individualized approach. Prescription decisions should be made based on evidence along with input from the patient and family, considering the health beliefs, prognosis, risk versus benefits, and quality of life.16
The prescriber might consider the acronym master when making prescribing decisions. This set of rules for rational drug therapy is as follows:
* Minimize the number of drugs used
* Alternatives should always be considered, especially nondrug therapies
* Start low and go slow
* Titrate therapy; adjust dose based on individual response
* Educate the patient and family; provide clear, written instructions
* Review regularly; remember that the older patient will need closer monitoring.19
Another model for prescribing for the elderly is the CARE model.
"C" is for caution. Is the drug necessary or will this condition resolve without medication? Use the lowest dose possible and prescribe for the shortest duration that is reasonable. "C" is also for compliance. Consider the form (use liquid if the patient has difficulty swallowing), cost, instructions, and functional limitations when ordering medication. "A" is for adjusting the dose for age. Older adults often need 1/4 to 1/2 of the usual starting dosage. They also have higher levels of body fat versus lean muscle mass and lower albumin levels so drugs that are fat soluble or highly protein bound need to be adjusted downward. "R" is for review. See the older patient more often and review the drug regimen at every visit. Finally, "E" is for educate. Make sure the patient or family member understands what the medication is for, what the therapeutic effect should be, how long before it is expected to produce results, and what possible adverse reactions could occur.8 This is especially important so that the patient does not stop taking the medication assuming that it is not working.
Conclusion
Prescribing for the older adult is challenging, complex, and not without risk. Understanding the age-related changes that affect the pharmacokinetics and pharmacodynamics of drugs is the foundation of prescribing for the older adult. Chronicity, multiple comorbidities, functional limitations, polypharmacy, and cost can all put the older patient at risk for over- or undertreatment of their medical conditions. Further, few clinical trials have included the old-old (75+) when establishing risk and efficacy. Employing these strategies to improve adherence, reduce risk, and maximize outcomes will assist the practitioner in safe and effective prescribing for the older patient.
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