Pharmacotherapy Principles in Older Adults

Richard G. Stefanacci

Older adults are the most pharmacotherapeutically challenging population because of the requirement to take into consideration their unique physiology and other factors in the face of the need to treat multiple chronic comorbid conditions. This warrants an understanding of aging and its effects on the body. Some of the other factors impacting this population include changes such as cognitive and social issues affecting proper adherence resulting in suboptimal outcomes. In addition, part of this challenge is the fact that many pharmaceuticals have not been testing in this population. As a result, practitioners need to rely on their knowledge of basic principles of pharmacotherapy in the older and monitor on an individual patient basis.

This expertise of managing pharmacotherapy in the older adults is crucial given that the older population is the fastest growing of any age group. By the year 2050, the “oldest old,” those aged 85 and older, will approach 19 million and 4.3% of the U.S. population (Vincent & Velhoff, 2010). The latest numbers available from the Centers for Disease Control and Prevention (CDC) reveal that 14.1% of the U.S. population is over the age of 65. Specifically, that population breaks down as shown in Table 6.1.

A report from National Center for Health Statistics, Division of Vital Statistics at the Centers for Disease Control and Prevention, finds an increase in overall life expectancy from 78.7 years in 2011 to 78.8 years in 2012. This is the longest life expectancy ever recorded, which they attribute to a reduction in many major causes of death, such as cancer, heart disease, and stroke. While decreasing in frequency, these remain significant health issues for older adults, which is a concern given the rise in obesity. Specifically, the CDC has identified certain overall health issues for older adults as described in Box 6.1.

The consequences of longevity are evidenced by the rising number of older adults living with multiple chronic diseases, contributing to disability, frailty, and decline in function and presenting significant challenges for medical management (Norris et al., 2008). This has led to an increased use of health care utilization, which the CDC reports as described in Box 6.2.

Treating multiple problems with prescription as well as over-the-counter (OTC) medications can result in adverse drug reactions (ADRs) and interactions related to changes produced by aging. Problems of polypharmacy (the use of an inappropriate amount of medications to treat a host of medical conditions), improper dosing for an older adult, and a lack of understanding by adults about medications can lead to significant but preventable adverse effects, such as falls, fractures, and delirium. This chapter discusses basic physiologic changes of aging, proper prescribing principles, and social concepts pertaining to safe medication use for the older adult.

BODY CHANGES AND AGING

Every body system is affected by the aging process, although homeostasis is often maintained despite less-than-optimal functioning of organ systems. Certain systems are more vitally affected by aging and play significant roles in the pharmacokinetic and pharmacodynamic changes in drug effects. Box 6.3 summarizes the impact of aging on the pharmacokinetics of drugs.

TABLE 6.1 Population by Age and Sex: 2012

	Both Sexes		Male		Female
Age	Number	Percent	Number	Percent	Number	Percent
All ages	308,827	100.0	151,175	100.0	157,653	100.0
55-59 y	20,470	6.6	9,879	6.5	10,592	6.7
60-64 y	17,501	5.7	8,278	5.5	9,223	5.8
65-69 y	13,599	4.4	6,461	4.3	7,139	4.5
70-74 y	9,784	3.2	4,519	3.0	5,265	3.3
75-79 y	7,331	2.4	3,122	2.1	4,209	2.7
80-84 y	5,786	1.9	2,421	1.6	3,365	2.1
85 y and over	5,006	1.6	1,809	1.2	3,196	2.0
Numbers in thousands. Civilian noninstitutionalized population.

Absorption

Older individuals frequently have oropharyngeal muscle dysmotility and altered swallowing of food. Reductions in esophageal peristalsis and lower esophageal sphincter (LES) pressures are also more common in the aged. Delayed motility and gastric emptying have been reported in some cases as well as the propulsive motility of the colon is also decreased, which may impact absorption. Decreased gastric secretions (acid, pepsin) and impairment of the mucous-bicarbonate barrier are frequently described in the older and may impact absorption. The prolonged transit time in the GI tract still allows for adequate drug absorption.

Distribution

Muscle that makes up lean body tissue decreases in the older adult, shifting to increased fat stores, and body water content decreases by 10% to 15% by age 80. Aging results in some reduction in serum albumin (by approximately 20%), leading to an increase in free drug concentration of drugs such as warfarin (Coumadin) and phenytoin (Dilantin).

There are two important plasma-binding proteins in drug metabolism: albumin and α-acid glycoprotein. Albumin has an affinity for acid compounds or drugs such as warfarin, whereas α₁-acid glycoprotein binds more readily with lipophilic and alkaline drugs such as propranolol (Inderal). The effects of chronic disease, nutritional deficits, immobility, and age-related liver changes contribute to the changes in serum proteins. The significance of decreased serum proteins is realized when highly protein-bound drugs compete for decreased protein-binding sites. The result can be greater levels of free or unbound circulating drug and, therefore, potential toxicity.

BOX 6.3
Guidelines for Safe Prescribing for Older Adults

INITIATION OF THERAPY

Review the risks and benefits of adding a medication. Explore nonpharmacologic options first.
If possible, choose one medication that treats two coexisting problems.
Always start with the lowest dose possible and titrate up slowly. “Start low; go slow.”
Choose a drug with the fewest daily required doses (i.e., daily vs. twice daily).
Remember to consider the cost of the brand name drug and consider generic equivalents if cost issues will deter compliance.

ONGOING PHARMACOTHERAPY ASSESSMENT

Schedule routine follow-up examinations for the patient who has multiple chronic illnesses and who takes multiple medications.
Reduce dosages or discontinue medications if possible to avoid polypharmacy.
Advise adults to bring all medications (prescription or OTC) to each office visit for review.
Document accurately all current medications and dosages.
Review medications added by other practitioners and specialists. Inform these professionals of changes made by the primary health care provider.
Schedule blood tests regularly to monitor levels of such medications as diuretics, ACE inhibitors, antiseizure medications, anticoagulants, antiarrhythmics, and digitalis.

PATIENT SUPPORT

Give a written list and instructions to the patient after each office visit of the medications to be taken.
Provide the written medication instructions and changes in large print in terms easily understood by older adults.
Explain and document both the generic and brand name of the prescribed drug to avoid confusing the patient as well as the important reason for each medication.
Review medications and changes in the regimen with family/caregivers especially for those caring for loved ones with cognitive impairments.
Recommend or provide medication planners or weekly/daily dosage containers to improve compliance and promote safe medication administration.

Body mass changes may lead to changes in total body content of drugs in older adults. A water-soluble drug (low volume of distribution [V_d]) is taken up more readily by lean tissue or muscle and attains higher serum concentrations in adults with less body water or lean tissue. Conversely, a lipid-soluble drug is retained in body fat, resulting in a higher V_d for some drugs. Coupled with a decrease or no change in total body clearance, this increase in V_d can lead to increased half-lives and drug accumulation in older adults. For example, diazepam (Valium) has a half-life (t_½) of approximately 20 hours in a young adult, but the t_½ can exceed 70 hours in the older adult. In addition, some drugs, such as tricyclic antidepressants (TCAs) and long-acting benzodiazepines, pass more readily through the blood-brain barrier, causing more pronounced central nervous system (CNS) effects. Older adults who are treated for depression and anxiety may experience fatigue and confusion from drug therapy because antidepressant and antianxiety agents more readily cross their blood-brain barrier.

Elimination

The liver is the major organ of drug metabolism in the body. With aging comes a decrease in blood flow and liver size. However, in the absence of disease, function is maintained. Decreased size and hepatic blood flow may slow the clearance of certain drugs, and reduced dosages may be required. This is particularly important for drugs with high hepatic extraction ratios. Phase I metabolism, particularly oxidation, is affected by aging. The result is decreased oxidation of drugs, which in turn results in a decreased total body clearance (Box 6.3). The phase II metabolism of drugs by conjugation, which promotes drug elimination by breaking the drug into water-soluble components, is not affected by age.

After the liver, the kidneys are the most important organs for drug metabolism and excretion. After age 40, renal blood flow declines and the glomerular filtration rate (GFR) drops approximately 1% a year and accelerates with advancing age. Function is usually maintained despite decreased filtration unless illness or disease overstresses the kidney (Kelleher & Lindeman, 2003). In older adults, drugs excreted primarily by the kidney are given in smaller doses, or the time between doses is extended.

A serum creatinine level alone cannot be used to estimate renal function in the aging person because reductions in lean body mass result in decreased rates of keratinase formation. This, coupled with the decreased GFR, makes the serum keratinase appear normal. It cannot be assumed that the GFR is normal from a normal serum creatinine value. The most
accurate means of measuring renal function is a 24-hour urine test for creatinine clearance; however, this is not standard procedure before ordering a medication. When there is a need to determine a drug choice in the setting of a potential reduction in creatinine clearance, the Cockcroft and Gault or the MDR formula (see Chapter 2) provides an estimate based on age, weight, and serum creatinine level with an adjustment for sex. Table 6.2 lists drugs eliminated by the kidney and recommended dosage adjustments based on estimated creatinine clearance.

TABLE 6.2 Examples of Dose Adjustments Based on Estimated Creatinine Clearance

	Dose Based on Estimated CrCl^*
Drug	Usual Oral Dose (Nonrenally Impaired)	CrCl >50 mL/min	CrCl 10-50 mL/min	CrCL <10 mL/min
amantadine	100 mg q12h	Usual dose	Increase interval to q24-72h	Increase interval to q7 days
amoxicillin	250-500 mg q8h	Usual dose	Increase interval to q12h	Increase interval to q24h
cefaclor	250 mg tid	Usual dose	Decrease dose to 50%-100% of usual	Decrease dose to 50% of usual
ciprofloxacin	250-750 mg q12h	Usual dose	Reduce dose to 50% of usual	Reduce dose to 33% of usual or extend to q24h
codeine	30-60 mg q4-6h	Usual dose	Reduce dose to 75% of usual	Reduce dose to 50% of usual
digoxin^†	0.125-0.5 mg q24h	Usual dose	Reduce dose to 25%-75% of usual OR increase interval to q48h	Reduce dose to 10%-25% of usual
enalapril	5-10 mg q12h	Usual dose	Reduce dose to 75% of usual 300 mg daily (for CrCl 15-30 mL/min)	Reduce dose to 50% of usual 300 mg every other day (for CrCl 15 mL/min)
gabapentin^†	400 mg tid (for CrCl >60)	300 mg bid (for CrCl 30-60 mL/min)
nadolol	80-120 mg/d	Usual dose	Reduce dose to 50% of usual	Reduce dose to 25% of usual
procainamide^‡	350-400 mg q3-4h	Usual dose	Increase interval to 6-12h	Increase interval to q8-24h
ranitidine	150 mg q12h or 300 mg qhs	Usual dose	Decrease dose to 50% of usual OR increase interval to q24h	Decrease dose to 25% of usual OR increase interval to q48h
^*Dose adjustments based on actual creatinine clearance or creatinine clearance estimated by the Cockroft and Gault formula (see Chapter 2). ^†These drugs are best monitored using actual drug levels, and dose adjustments should be made based on these results. ^‡Based on manufacturer’s information.

PHARMACODYNAMIC CHANGES IN THE OLDER ADULT

Many of the changes that occur due to aging affect major organ systems and therefore affect the pharmacokinetic disposition of the drug. However, the clinician also must consider the impact drugs have on the aging body, the pharmacodynamic effect. Although few data are available regarding age-related pharmacodynamic changes in older adults, it is known that the older adult may be more sensitive to drug-receptor interactions, because of either increased sensitivity of the receptor to the drug or decreased capacity to respond to drug-induced innervation of receptors. In addition, the number or affinity of receptors may be reduced. Nevertheless, it is commonly accepted that the CNS effects of drugs appear to be exaggerated in the older patient. Particularly egregious are the agents with anticholinergic effects, such as the TCAs, antihistamines, and antispasmodics. The anticholinergic effect induced by these agents can lead to excessive dry mouth, blurred vision, constipation, and even an exacerbation of benign prostatic hyperplasia in men. Caution should be used if these agents are prescribed at all.

Similarly, the sedative effects of agents may be intensified in older adults. The benzodiazepines and potent analgesic agents are examples of drugs for which older adults are particularly susceptible to this adverse effect. Overprescribing, or typical prescribing without considering the potential for exaggerated effect, can lead to oversedation and a greater risk of falls and fractures.

The cardiovascular system also can be affected by changes due to aging. Orthostatic hypotension is more common in the older adult because of a loss of the baroreceptor reflex and changes in cerebral blood flow. Moreover, drugs that lower blood pressure or decrease cardiac output put the older patient at risk for a syncopal episode.

POLYPHARMACY

Polypharmacy is a significant factor in the morbidity and mortality of older adults. Increasing age puts the person at risk for multiple chronic illnesses, many of which require drug therapy For example, the most common chronic disease in the United States, osteoarthritis, affects 40 million people, the majority being older adults. The costs in terms of morbidity are staggering. Chronic stiffness and pain from arthritis have an impact on function, prompting the routine use of nonsteroidal
anti-inflammatory drugs (NSAIDs) and aspirin products. Long-term use of NSAIDs lowers the prostaglandin level in the GI tract, which may result in esophagitis, peptic ulcerations, GI hemorrhage, and GI perforation. In an older adult, treatment with histamine-2 blockers or proton pump inhibitors to relieve the side effects of aspirin or other NSAIDs may cause additional side effects, such as confusion and mental status changes, in turn requiring more treatment. This demonstrates how easily adverse events occur and snowball in an older patient. ADRs account for 30% of hospital admissions for persons older than age 65; approximately 106,000 deaths are attributed to medication problems. Sadly, 15% to 65% of these events are preventable (Shiyanbola & Farris, 2010) by avoiding potentially inappropriate medications, effective communication, and patient education.

Several factors contribute to polypharmacy. Among them are the varied symptoms and complaints associated with multiple chronic illnesses. In addition, adults often believe that a “pill will fix what ails them,” and the health care provider feels pressured to “prescribe something” to satisfy the adults’ expectations of a prescription for medication. When a particular medication regimen is unsuccessful, the health care provider typically prescribes another drug, this is referred to as the prescribing cascade. Dr. Jerry Gurwitz, a noted geriatrician, has attributed the caveat that “Any symptom in an elderly patient should be considered a drug side effect until proved otherwise,” although his wife, Leslie Fine, a pharmacist, is actually believed to have first described this approach (Smith, 2013).

Polypharmacy is also the effect from many older adults stockpiling their discontinued medications in case they may be needed again—primarily because of the cost of prescription drugs. Many providers who visit older adults in their homes have seen evidence of stockpiled medications. Some older adults keep a drawer or cabinet full of old prescription drug bottles. Some contain the same medication, differing only in brand name. Some adults may place a current medication (prescription or OTC) in a labeled prescription bottle that was used for another drug. In addition, the stockpile may reveal prescription bottles for other family members. Adults may be sharing medications or may have received medications from others who believed that the drug that helped them would help the patient.

Other sources of polypharmacy are “polyproviders.” Many older adults see multiple specialists for various chronic diseases. Medications prescribed without the provider carefully reviewing the patient’s other medications can lead to drug overuse and complications. Without a primary care provider overseeing the care of the older adult seeing multiple specialists, ADRs are sure to occur.

The health care provider sometimes creates a polypharmacy situation because multiple drugs are used to treat several chronic illnesses. The provider who is not astute in the principles of safe geriatric prescribing practices may create avoidable side effects and complications. In addition, the patient, who may be a great consumer of OTC medications or home remedies, often self-prescribes without knowing the consequences of mixing these treatments with current prescription drugs.

Drug Interactions in the Older Adult

Because of normal, age-related physiologic changes, the older adult is at greater risk for complications from medications. Complications related to drug-disease, drug-drug, and drug-food interaction are all commonly encountered. (For more information on drug-drug interactions, see Chapter 3.)

Adverse Drug Reactions

ADRs often result in significant negative health outcomes, such as falls and fractures, costing billions of dollars in hospital and nursing home care (Shiyanbola & Farris, 2010). Although age itself creates a risk for ADRs, polypharmacy and the multiplicity of drugs taken by older adults present the greater risk. The older adult with multiple chronic illnesses and medications must be identified as a potential candidate for ADRs (Fick et al., 2003). Older women in particular are at great risk for ADRs because they often receive more prescription drugs and have a more significant loss of muscle mass than older men.

There is a paucity of information on safety and efficacy of drugs for the older patient. Most research and clinical trials are performed with younger subjects. It often is difficult or impossible to predict the consequences of a medication for its intended use on an older adult because few data may be available. In an effort to better understand the effects of drugs on older adults, the U.S. Food and Drug Administration published guidelines in 1997 recommending older adults be included in clinical trials of drugs specifically being developed to treat prevalent diseases affecting older adults (Murray & Callahan, 2003).

Contributing Lifestyle Factors

Preventing adverse events or failed treatments begins with being unaware of potential drug interactions resulting from older adults commonly taking OTC medications and prescription drugs without alerting their health care providers. Additional combinations of foods or nutritional supplements can slow absorption, prolonging the time for medications to reach peak levels (see Chapter 3). Fatty foods, in particular, can increase intestinal drug absorption because of the longer time required to digest a fatty meal. This, in turn, potentially leads to increased drug levels or toxicity.

Alcohol and Other Drugs

The ingestion of alcohol and other drugs can alter the metabolism of many medications in older adults. The combination of comorbid conditions, physiological changes with age, and concomitant medications is often potentiated with alcohol usage. CNS effects such as lethargy and confusion occur, as does hypotension, when alcohol is combined with nitrates and some cardiovascular drugs. Alcohol can be found in many OTC products such as cough and cold syrups and mouthwashes.

Alcohol abuse may be overlooked as a potential problem in the older adult, but abuse among community-dwelling
(noninstitutionalized) people age 65 and older has a prevalence of 14% for men and 1.5% for women. High numbers of older alcoholics are treated in emergency departments and medical offices or are hospitalized for medical or psychiatric admissions. Depression, which is more prevalent in the older, often coexists with alcohol abuse. Moderate-to-heavy drinkers older than 65 are 16 times more likely to die of suicide. Practitioners need to be more aware of the potential for alcohol abuse in older adults. Although alcohol use and abuse decline with age, approximately 40% of older adults use alcohol, with between 2% and 4% meeting the criteria for alcohol abuse/dependency. The use of alcohol is anticipated to increase as baby boomers age. The baby boomer cohort has a history of greater alcohol, tobacco, and nonmedical substance usage than previous generations. Life stressors such as retirement, loss of loved ones, dependency, and chronic illness are contributors to potential alcohol abuse. Also, as more and more states follow Washington and Colorado’s lead in legalizing the recreational use of marijuana, it should be expected that older adults will also be among the users. So the inclusion of this potential drug-drug interaction needs to be taken into account as well.

Caffeine and Nicotine Use

Caffeine and nicotine are among some of the most commonly used products that have the potential to interact with certain drugs, thereby altering efficacy and therapeutic drug levels. Besides its presence in coffee, tea, and some sodas, caffeine is found in many OTC drug products. The interaction of caffeine and certain medications may alter drug absorption, cause CNS effects, or decrease drug effectiveness. Table 6.3 summarizes selected caffeine-medication interactions.

TABLE 6.3 Medication-Caffeine Interactions

Type of Interaction	Example of Interaction Effect
Caffeine-induced increase in gastric acid secretion	Decreased absorption of iron
Caffeine-induced gastrointestinal irritation	Decreased effectiveness of cimetidine; increased gastrointestinal irritation from corticosteroids, alcohol, and analgesics
Altered caffeine metabolism	Prolonged effect of caffeine when combined with ciprofloxacin, estrogen, or cimetidine
Caffeine-induced cardiac arrhythmic effect	Decreased effectiveness of antiarrhythmic medications
Caffeine-induced hypokalemia	Exacerbated hypokalemic effect of diuretics
Caffeine-induced stimulation of CNS	Increased stimulation effects from amantadine, decongestants, fluoxetine, and theophylline
Caffeine-induced increase in excretion of lithium	Decreased effectiveness of lithium

TABLE 6.4 Medication-Nicotine Interactions

Type of Interaction	Example of Interaction Effect
Nicotine-induced alteration in metabolism	Decreased efficacy of analgesics, lorazepam, theophylline, aminophylline, β-blockers, and calcium channel blockers
Nicotine-induced vasoconstriction	Increased peripheral ischemic effect of β-blockers
Nicotine-induced CNS stimulation	Decreased drowsiness from benzodiazepines and phenothiazines
Nicotine-induced stimulation of antidiuretic hormone secretion	Fluid retention and decreased effectiveness of diuretics
Nicotine-induced increase in platelet activity	Decreased anticoagulant effectiveness (heparin, warfarin); increased risk of thrombosis with estrogen use
Nicotine-induced increase in gastric acid	Decreased or negated effects of H₂ antagonists (cimetidine, famotidine, nizatidine, ranitidine)

Many older adults have lifelong smoking addictions and are unsuccessful in stopping. Adults and providers alike are frequently unaware of the effects of nicotine and medications. Nicotine alters the metabolism of many drugs, causes CNS effects, and interferes with platelet activity. Table 6.4 reviews nicotine-medication effects and interactions.

ADHERENCE ISSUES

One reason older adults, similar to all patients, do not achieve the optimum outcome from their treatments is their failure to adhere to the medication regimen. In many cases, prescription drugs are not taken as prescribed: up to 40% of older adults take their medications improperly. More than 40% of ambulatory adults age 65 and older take at least 5 medications per week, with 12% taking at least 10 per week. Studies have shown that as the complexity of the medication regime increases, improper drug usage rises proportionately. In some cases, they may not take enough of the medication, either because they think that they will save money by making the prescription last longer or because they believe that the medicine is not needed at the prescribed dose. In other situations, a medication may not be taken if it interferes with the patient’s lifestyle, for example, not taking a diuretic for fear of incontinence on certain days.

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Tags: Pharmacotherapeutics for Advanced Practice: A Practical Approach

Nov 11, 2018 | Posted by drzezo in PHARMACY | Comments Off

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