CHAPTER 8 - APPENDIX Chapters in Which Assessment

APPENDIX Chapters in Which Assessment

CHAPTER 8 CHAPTER 8

evolve.elsevier.com/Ebersole/gerontological

Safe Medication Use

Kathleen F. Jett

I

n the United States, persons 65 years of age and older are the largest users of prescription and over-the-counter (OTC) medications; with the number of medications taken increasing with age.

Making up only 13% of the population, they consume 33% of the prescribed medications or a range some- where between 0 and 13 prescription drugs per person, and about 40% of OTC medications or other supple- ments such as herbs (Steinman et al., 2006; Gallagher et al., 2007; Brandt, 2010). Ninety percent of the persons at least 65 years of age take at least 1 drug a week, over 40% take at least 5, and 12% use at least 10 different drugs every week. Residents of long-term care facilities take the most medications of all, typically 7 to 8 different ones (Ruscin, 2009; Brandt, 2010). Elders accumulate prescriptions as they accumulate chronic diseases and number of health care providers (Green et al., 2007).

Unfortunately, the number of adverse drug reactions increases with the number of medications used. Adverse drug reactions (ADRs) have been found to be a notable cause for hospitalization as well as a cause of iatrogenic mortality and morbidity for those already hospitalized. This has been found to occur not only in the United States but in countries across the globe.

How elders use their prescribed medicines and other bioactive products depends on many factors related to the person’s own unique characteristics, situations, beliefs, understanding about illness, functional and cognitive status, perception of the necessity of the drugs, severity of symptoms, reactions to the medications, finances, access, and alternatives, and the compatibility of such products with their lifestyle. From the perspective of Maslow’s Hierarchy of Needs, drugs impinge on all levels. When used appropriately, prescription medications can afford basic survival or even enhance one’s quality of life and help achieve self-actualization for those with chronic conditions and disabilities. When they are used inappro- priately, they threaten even the most basic level of physiological stability. Yet, at times, even when drugs are used appropriately, they may adversely affect the elder’s health and well-being.

Gerontological nurses have a responsibility to help minimize the risks and maximize the safety of medication use in the persons who receive their care. A review of the changes in pharmacokinetics, pharmacodynamics, and is- sues in drug use are presented in this chapter. The final section deals with the use of psychotropic agents. These are frequently prescribed to frail elders with the potential for both great benefit and significant risk and require special attention.

Pharmacokinetics

The term pharmacokinetics refers to the movement of a drug in the body from the point of administration as it is absorbed, distributed, metabolized, and finally, excreted.

There is no conclusive evidence of an appreciable change in overall pharmacokinetics with aging; however, there are several changes with aging (see Chapter 5) that may have an effect (Figure 8-1). This chapter is not intended to re- place a pharmacology text, but to supplement it for the key points of intersection between safe medication use and the aging process.

Absorption

For a drug to be effective it must be absorbed into the blood stream. The amount of time between the administration of the drug and its absorption depends on a number of factors, including the route of introduction (i.e., intravenous, oral, parenteral, transdermal, or rectal), bioavailabil- ity, and the amount of drug that passes into the body. The drug is delivered immediately to the blood stream with administration by intravenous route, and quickly with parenteral and transdermal routes and through mucous membranes such as the rectum and the oral mucosa. Orally administered drugs are absorbed the most slowly through the gastrointestinal tract.

Several normal age-related physiological changes have implications for differences in both the prescribing and the administration of medications for older adults (Table 8-1).

The commonly seen increased gastric pH will retard the action of acid-dependent drugs. Delayed stomach empty- ing may diminish or negate the effectiveness of short-lived drugs that could become inactivated before reaching the small intestine. The absorption of some enteric-coated medications, such as enteric-coated aspirin, which are specifically meant to bypass stomach absorption, may be delayed so long that their action begins in the stomach and may produce gastric irritation or nausea. Absorption is also influenced by changes in gastrointestinal motility. If there is increased motility in the small intestine, drug effect is diminished because of shortened contact time and therefore decreased absorption and effectiveness. Conversely, slowed intestinal motility can increase the contact time and therefore the amount absorbed and the drug’s effect.

This increases the risk for adverse reactions or unpredict- able effects.

Many medications commonly taken by older adults can also affect the absorption of other drugs. Antispas- modic drugs slow gastric and intestinal motility. In some instances the ingested drug’s action may be useful, but

when there are other medications involved, it is necessary to consider the problem of drug absorption alterations due to drug-drug interaction. Antacids or iron preparations affect the availability of some drugs for absorption by binding the drug with elements and forming chemical compounds. Drug-food interactions may either decrease or increase the amount absorbed. For example when a bisphosphonate such as Fosamax is taken with food of any kind, the absorption is reduced to only a few milli- grams, and therefore the drug has no effect on the target organ, the bones; if thyroxin is taken at the same time

as any compounds such as calcium or magnesium, it is inactivated.

Distribution

When a drug is absorbed it must be transported to the receptor site on the target organ to have any effect. Distri- bution depends on the availability of plasma protein in the form of lipoproteins, globulins, and especially albumin. As drugs are absorbed, they bind with the protein and are distributed throughout the body. Normally, a predictable

↓ Renal blood flow

↓ Glomerular filtration rate

↓ Tubular secretory function

↓ Hepatic blood flow

↓ Hepatic mass

↓ Enzyme activity

↓ Enzyme inductibility

↓ Total body water

↓ Cardiac output

↓ Lean body mass

↑ Body fat

↓ Absorptive surface

↑ Gastric pH

↓ Splanchnic blood flow

↓ Gastrointestinal activity

↓ Serum albumin

↓ Protein binding

Site of administration

Distribution (blood) Absorption

Elimination Plasma level

Bound Free (plasma protein)

Site of action (receptor sites)

Response

PHARMACODYNAMICSPHARMACOKINETICS

Side effects Toxicity

Tissue (depots) Biotransformation

(liver, blood)

FIGURE 8-1 Physiological changes of aging and the pharmacokinetics and pharmacodynamics of drug use. (Data from Kane RL, Ouslander JG, Abrass IB: Essentials of clinical geriatrics, New York, 1984, McGraw-Hill; Lamy PP: Hazards of drug use in the elderly: commonsense measures to reduce them, Postgrad Med 76(1):50-53, 1984; Vestal RE, Dawson GW: Pharmacology and aging. In Finch CE, Schneider EL, editors: Handbook of biology and aging, New York, 1985, Van Nostrand Reinhold; Roberts J, Tumer N: Pharmacodynamic basis for altered drug action in the elderly, Clin Geriatr Med 4(1):127-149, 1988; Montamat SC, Cusack BJ, Vestal RE: Management of drug therapy in the elderly, N Engl J Med 321(5):303-309, 1989.)

percentage of the absorbed drug is inactivated as it is bound to the protein. The remaining free drug is available in the blood stream and has therapeutic effect when an effective concentration is reached in the plasma. Many older adults have an insignificant reduction in the serum albumin level. In others, especially those with prolonged illness or malnutrition (such as residents in skilled nursing facilities), the serum albumin may become dramatically diminished. When this occurs, toxic levels of available free drug may accumulate unpredictably, especially of highly protein-bound medications with narrow therapeutic win- dows, such as phenytoin and warfarin (Ruscin, 2009).

Potential alterations of drug distribution in late life are related to changes in body composition, particularly decreased lean body mass, increased body fat, and decreased total body water (see Figure 8-1). Decreased body water leads to higher serum levels of water-soluble drugs, such as lithium, digoxin, ethanol, and aminoglycosides. Increased serum levels increase the risk for toxicity. Adipose tissue nearly doubles in older men and increases by one half in older women; therefore drugs that are highly lipid-soluble are stored in the fatty tissue, extending and possibly elevat- ing the drug effect (Masoro & Austed, 2003). This affects drugs such as lorazepam, diazepam, chlorpromazine, phe- nobarbital, and haloperidol (Haldol).

Metabolism

Biotransformation or metabolism, is the process by which the body modifies the chemical structure of the drug.

Through this process the compound is converted to a metabolite that is later more easily excreted. A drug will continue to exert a therapeutic effect as long as it remains in either its original state or as an active metabolite. Active metabolites retain the ability to have a therapeutic effect, as well as the same or a greater chance of causing adverse effects. For example, the metabolites of acetaminophen (Tylenol) can cause liver damage with higher dosages (. 4 g/24 hr or more than four extra-strength products).

The duration of drug action is determined by the metabolic rate and is measured in terms of half-life, or how long the drug remains active in the body.

A number of enzymes play an active part in drug metabolism. Among these are a group known as the cytochrome P450 (CYP450) monooxygenase system. The system is made up of about 50 isoforms, each of which has the potential to metabolize a drug by adding or subtracting part of the drug molecule. When this occurs the drug can be dramatically changed from its original state or even its intended effect. While age does not appear to affect the functioning of the CYP450 system, we now know that genetics have a great effect (Box 8-1).

TABLE

8-1

Interaction of Aging and Drug Response, Select Medications

Class Drug Effect of Aging

Analgesic Morphine h analgesia

Anticoagulant Warfarin (Coumadin)

h blood time Bronchodilator Albuterol g bronchodilation Cardiovascular

agents ACE IIs

Enalapril Diltiazem Verapamil

h BP reduction h BP reduction h acute reduction in BP h acute reduction in BP

Diuretic Furosemide

(Lasix)

g maximum response

Other Levodopa h side effects

From Ruscin JM: Drug therapy in the elderly. In The Merck manual for health professionals – Epub. Last updated September 2009. Available at http://www.merckmanuals.com/professional/geriatrics/drug_therapy_

in_the_elderly/drug-related_problems_in_the_elderly.html#v1133742.

As knowledge of genetics explodes, so does our ability to consider the possibility of what has come to be called

“personalized medicine.” Included in this is consideration of someday selecting medications and formulations con- sistent with the metabolic enzymes specific to the individual, which should optimize therapeutic effect while minimizing or eliminating any untoward effects. Cyto- chrome P450 refers to a group of enzymes found primarily in the liver and responsible for the metabolism and excretion of the majority of drugs. Four phenotypic categories of persons relative to the speed of P450 metabolism have been identified. Someone who is a “poor” or “slow”

metabolizer will excrete more slowly and therefore can achieve the same therapeutic effect with a low dose of a medication compared with the high dose needed by a

“rapid” or even “ultrarapid” metabolizer. Among persons from the regions of northern Europe, 5% to 10% are poor metabolizers. This contrasts with persons from parts of Asia and Africa, among whom only 1% are poor metabolizers.

BOX

8-1

Focus on Genetics

From Bartlett D: Drug therapy gets personal with genetic profiling. Am Nurse Today 6(5):23-28, 2011; Tiwari AK, Souza RP, Muller DJ: Pharmacogenetics of anxiolytic drugs. J Neural Transm 116:667, 2009.

The liver is the primary site of drug metabolism. With aging, the liver’s activity, mass, volume, and blood flow are reduced and hepatic clearance may decrease by up to 30%

to 40% (Ruscin, 2009). These changes result in a potential decrease in the liver’s ability to metabolize drugs such as benzodiazepines (e.g., the tranquilizer lorazepam [Ativan]) (Table 8-2). These changes result in a significant increase in the half-life of these drugs. For example, the half-life of diazepam (Valium) in a younger adult is about 37 hours, but in an older adult extends to as long as 82 hours. If the dose and timing are not adjusted, the drug can accumulate, and the administration of a single dose can have significantly more effects (and longer) than in a younger person.

Except in the rarest of circumstances Valium should not be used because of this (American Geriatrics Society [AGS], 2012).

Excretion

Drugs and their metabolites are excreted in sweat, saliva, and other secretions but primarily through the kidneys.

However, because kidney function declines significantly in aging (up to 50% decrease by the time one is 80 years of age), so does the ability to excrete or eliminate drugs in a timely manner (see Table 8-2). The considerably decreased glomerular filtration rate leads to prolongation of the half- life of drugs, or the amount of time required to eliminate the drug, again presenting opportunities for accumulation and increasing the potential for toxicity or other adverse events. Although renal function is highly individualized and cannot be estimated by the serum creatinine level, we approximate it by calculating the creatinine clearance (see equation). Reductions in dosages for drugs excreted by the kidneys (e.g., allopurinol, vancomycin) are needed when the creatinine clearance is reduced. Reductions in dosages may also be needed when the patient is very ill or dehydrated.

Estimated creatinine clearance (the Cockcroft-Gault equation):

TABLE

8-2

Class or category

Affected by Decreased Hepatic Metabolism

Affected By Decreased Renal Excretion Analgesic/

antiinflamatory Ibuprofen (Advil) Naproxen (Aleve) Morphine

Antibiotics Cipro

Macrobid Cardiovascular Amlodipine

(Norvasc) Captopril (Capoten) Diltiazem

(Cardizem) Digoxin (Lanoxin) Verapamil (Calan) Enalapril (Vasotec)

Lisinopril (Zestril)

Diuretics Furosemide

(Lasix) HCTZ

Others Levodopa Glyburide

Ranitidine (Axid) Psychoactive drugs Alprazolam (Xanax) Risperidone

Diazepam (Valium) Trazadone

the_elderly/drug-related_problems_in_the_elderly.html#v1133742.

Drugs to Watch: Examples of Commonly Used Medications Affected by Normal Changes with Aging

(140 age) wt (kg) ( 0.85 only if femalee) (serum creatinine 72)

For alternative calculations, see http://nkdep.nih.gov/

professionals/gfr_calculators.

Pharmacodynamics

Pharmacodynamics refers to the interaction between a drug and the body (see Figure 8-1). The older the person gets, the more likely there will be an altered or unreliable response of the body to the drug. Although it is not al- ways possible to explain the change in response, several mechanisms are known. For example, the aging process causes a decreased response to beta-adrenergic receptor stimulators and blockers; decreased baroreceptor sensitivity; and increased sensitivity to a number of medications, especially anticholinergics, benzodiazepines, nar- cotic analgesics, warfarin (Coumadin), and the cardiac drugs diltiazem and verapamil (Briggs, 2005). If food- drug interactions occur, the problems are worsened.

For example, drinking grapefruit juice at the same time as one takes a “statin” such as Lipitor or any number of antibiotics may cause an unreliable response. There is also a growing body of knowledge about the interaction of herbal preparations and currently prescribed medications (Table 8-3). For example, ginkgo biloba is commonly thought to enhance cognitive function.

TABLE

8-3

Selected Herb-Medication and Herb-Disease Interactions

Herb Medication Complication Nursing Action

Chamomile Warfarin May increase risk of bleeding Advise to avoid teas and other products which contain the product Garlic Warfarin or any anticoagulant

or antiplatelet drug Risk of bleeding increases Advise client not to take without provider approval

NSAIDs

Anticlotting drugs such as

streptokinase and urokinase May decrease effect Advise against use Antihypertensives May increase antihypertensive

effect Monitor BP

Antihyperglycemic drugs Serum glucose control may improve, lowering the amount of medication needed

Monitor blood glucose levels

Ginkgo Aspirin

Heparin and warfarin Risk of bleeding increases Teach client not to take without approval of provider Antihyperglycemic drugs May alter blood glucose levels Monitor blood glucose closely Antihypertensives

Nifedipine May cause increased effect Monitor blood pressure

Ginseng Antihyperglycemic drugs May intensify effect Monitor for hypoglycemia Anticoagulants and

antiplatelet drugs May increase bleeding Advise use with caution Corticosteroids May interfere with action Advise against use

Digoxin May increase blood level Advise against use

Green tea Warfarin May alter anticoagulant effects Advise against use

Hawthorn Digoxin May cause a loss of potassium,

leading to drug toxicity Monitor blood levels Beta blockers and other drugs

lowering blood pressure and improving blood flow

May be additive in effects Monitor blood pressure meticulously;

advise that this concern extends to erectile dysfunction drugs also St. John’s wort HMG-CoA reductase inhibitors

(e.g., Lipitor, simvistatin) May decrease plasma

concentrations of these drugs Monitor levels of lipids Digoxin Decreases the effects of the drug Advise against use Alprazolam (Xanax) May decrease effect of drug Advise against use Efavirenz and other anti-HIVs May decrease drug level Advise against use Photosensitizing drugs (e.g.,

NSAIDs, some antibiotics) Increased photosensitivity Advise sun block use

Tramadol May increase risk of serotonin

syndrome Advise against use

Olanzapine (Zyprexa) May cause serotonin syndrome Advise against use

SSRIs (e.g., Xoloft) Excessive sedation Advise against use

Albuterol Decreases effect Monitor drug effects

Warfarin (Coumadin) May decrease anticoagulant

effect Advise against use

Amlodipine Lowers efficacy of calcium

channel Advise against use

HIV, Human immunodeficiency virus; HMG-CoA, 3-hydroxy-3-methylglutaryl coenzyme A; NSAIDs, nonsteroidal antiinflammatory drugs; SSRIs, selective serotonin reuptake inhibitors.

From Basch E, Ulbricht C: Natural standard herb & supplement handbook: the clinical bottom line, St. Louis, 2005, Mosby; Jellin JM, editor: Natural medicines comprehensive database (2006). Available at www.naturaldatabase.com/; NDH pocket guide to drug interactions, Philadelphia, 2002, Lippincott, Williams & Wilkins; Yoon SL, Schaffer SD: Herbal, prescribed, and over-the-counter drug use in older women: prevalence of drug interactions, Geriatr Nurs 27(2):118-129, 2006; Merck Sharp & Dohme Corp: Some possible dietary supplement-drug interactions. In The Merck manual for health care professionals (2011). Available at http://www.merckmanuals.com/media/professional/pdf/Table_331-1.pdf.

Medication-Related Problems and Older Adults

Polypharmacy

Although there is controversy about how many drugs are “too many,” polypharmacy is the term used to indicate multiple drug use, and usually this implies the use of some drugs that are duplicated or unnecessary (Figure 8-2).

Junius-Walker and colleagues (2007) define polypharmacy as taking more than five medications at the same time. In their study of German elders, the average number of prescribed However, it will increase the potential for bleeding when

an anticoagulant such as Coumadin is used at the same time (Youngkin, 2012). In addition to the expected dry mouth, drugs with anticholinergic properties can cause confusion, constipation, blurred vision, orthostatic hypo- tension, urinary retention, or heat stroke, even at low doses (Ruscin, 2009). The use of benzodiazepines is associated with an increased risk for accidental injury, and they are on the “do-not-use” list for older adults (AGS, 2012).

Chronopharmacology

Another factor that affects both pharmacokinetics and pharmacodynamics are the normal biorhythms of the body. The relationship of biological rhythms to variations in the body’s response to drugs is known as chronopharmacology. Although it has not yet been explored in aging, chronopharmacology is a developing science that may lead to more effective drug therapy (Ohdo, 2010). The best time to administer medications is now being considered in light of the biorhythms of various physiological processes. For example, if a cortisone tablet (e.g., from a Medrol dose pak) is taken in the morning it suppresses the adrenocortical system very little. If the same dose were given divided over the day, unwanted effects of the drug will occur from suppression of the hypothalamus- pituitary-adrenal axis.

As noted earlier, absorption depends on gastric acid pH, the level of motility of the gastrointestinal tract, and blood flow. All have been shown to have biorhythmical variations. Distribution of protein-bound drugs depends on albumin and glycoproteins produced by the liver.

During the day, albumin levels are high, but they are low in the early morning. Drug metabolism is also biorhythmical due to changes in the liver over the course of the day.

Renal elimination depends on kidney perfusion, glomerular filtration, and urine acidity and has shown rhythmic variation. The brain, the heart, and blood cells have also been found to have varied rhythmicity, resulting in a cycli- cal response for beta blockers, calcium channel blockers, angiotensin-converting enzyme (ACE) inhibitors, nitrates, and other, similar drugs. Table 8-4 shows some of the rhythmical influences on diseases and physiological processes.

As more is learned about chronotherapeutics, the potential for decreasing individual doses of medications and/

or the frequency of administration is present. As we are able to do so we will be able to significantly decrease the potential for adverse drug events while maximizing therapeutic effects.

TABLE

8-4

Rhythmical Influences on Disease and Physiological Processes Disease or

Process Rhythmical Influence Allergic rhinitis Symptoms worse in the morning Arterial blood

pressure Circadian surge—morning hours Asthma Greatest respiratory distress

overnight (during sleeping) Symptoms peak in early morning

(4 to 5 am)

Blood plasma Plasma volume falls at night, thus hematocrit increases

Cancer Tumor cells proliferate when normal cell miosis is low

Cardiac disease Angina, myocardial infarction, thrombolytic stroke occur in the first 4 hours after waking (peak 9 am) (through 10 pm)

(Prinzmetal’s angina—during sleep) Catecholamines Increase in early morning Fibrinolytic activity Increase in early morning Platelet activation May result from abnormality in

circadian rhythm, which affects cortisol levels, body temperature, sleep-wake cycle

Gastric system Gastric acid secretion peaks every morning (2 to 4 am); circannual variability—incidence of gastric ulcers greater in winter Osteoarthritis Pain more severe in morning Potassium excretion Lowest in morning; highest in late

afternoon

Rheumatoid arthritis Pain more severe in late afternoon Systemic insulin Highest in afternoon

Dalam dokumen Ebersole and Hess' gerontological nursing & healthy aging (Halaman 121-135)