15 - Health Services

Editors: Kane, Robert L.; Ouslander, Joseph G.; Abrass, Itamar B.

Title: Essentials of Clinical Geriatrics, 5th Edition

Copyright 2004 McGraw-Hill

> Table of Contents > Part III - General Management Strategies > Chapter 14 - Drug Therapy

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Chapter 14

Drug Therapy

Geriatric patients are frequently prescribed multiple drugs in complex dosage schedules. In some instances, this is justified because of the presence of multiple chronic medical conditions, the proven efficacy of an increasing number of drugs for these conditions, and practice guidelines that recommend their use. In many instances, however, complex drug regimens are unnecessary; they are costly and predispose to noncompliance and adverse drug reactions. Many older patients are prescribed multiple drugs, take over-the-counter drugs, and are then prescribed additional drugs to treat the side effects of medications they are already taking. This scenario can result in an upward spiral in the number of drugs being taken and commonly leads to polypharmacy.

Several important considerations, some pharmacological and others nonpharmacological, influence the safety and effectiveness of drug therapy in the geriatric population. This chapter focuses on these considerations and gives practical suggestions for prescribing drugs for older patients. Drug therapy for specific geriatric conditions is discussed in several other chapters throughout this text.

NONPHARMACOLOGICAL FACTORS INFLUENCING DRUG THERAPY

Discussions of geriatric pharmacology frequently center around age-related changes in drug pharmacokinetics and pharmacodynamics. Although these changes are sometimes of clinical importance, nonpharmacological factors can play an even greater role in the safety and effectiveness of drug therapy in the geriatric population. Several steps make drug therapy safe and effective (Fig. 14-1). Many factors can interfere with this scheme in the geriatric population, and, as can be seen, most of them come into play before pharmacological considerations arise.

FIGURE 14-1 Factors that can interfere with successful drug therapy.

Effective drug therapy can be hampered by inaccurate diagnoses. Many older patients tend to underreport symptoms; complaints of other patients may be vague and multiple. Symptoms of physical diseases frequently overlap with symptoms of psychological illness. To add to this complexity, many diseases present with atypical symptoms. Consequently, making the correct diagnoses and prescribing the appropriate drugs are often difficult tasks in the geriatric population.

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There is a tendency among health care professionals to treat symptoms with drugs rather than to evaluate the symptoms thoroughly. Because older patients tend to have multiple problems and complaints and consult several health care professionals, they often end up with prescriptions for several drugs. Moreover, older patients or their family members sometimes exert pressure on health care professionals to prescribe medication, thus adding to the tendency for polypharmacy. This pressure is increasing because of the new trend of direct-to-consumer advertising of drugs.

Frequently, neither the patients nor the health care providers have a clear picture of the total drug regimen. New patients undergoing initial geriatric assessment should be asked to empty their medicine cabinets and to bring all bottles to their first appointments. Medication records, such as the one shown in Fig. 14-2, carried by the patient and maintained as an integral part of the overall medical

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record, may help to eliminate some of the polypharmacy and noncompliance common in the geriatric population. Such records should be updated at each patient visit. Drug regimens should be simplified whenever possible and patients instructed to discard old medications.

FIGURE 14-2 Example of a medication record.

Adherence plays a central role in the success of drug therapy in all age groups (see Fig. 14-1). In addition to the tendency for polypharmacy and complex dosage schedules, older patients face other potential barriers to adherence. The chronic nature of illness in the geriatric population can play a role in nonadherence. The consequences of these illnesses are often delayed (as opposed to the more dramatic effects of acute illnesses), and chronic illnesses necessitate ongoing prophylactic or suppressive rather than relatively short and time-limited courses of therapy. Adherence tends to be poor for these types of drug regimens. Diminished hearing, impaired vision, and poor literacy, and poor short-term memory can interfere with patient education and adherence. Problems with transportation can make getting to a pharmacy difficult. Outpatient prescriptions are not covered by Medicare (as of June, 2003), thus forcing older persons to pay for their drugs from a limited income. A Medicare prescription benefit will help, but is likely to be limited and involve substantial copayments. Some older people have Medigap insurance policies that cover some medication costs, and capitated

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programs commonly offer drug benefits (usually limited to a formulary and generic drugs when available). Even if the older person gets to the pharmacy, can afford the prescription, understands the instructions, and remembers when to take it, the use of childproof bottles and tamper-resistant packaging may hinder adherence in those with arthritic or weak hands.

Several strategies might improve adherence in the geriatric population (Table 14-1). As few drugs as possible should be prescribed, and the dosage schedule should be as simple as possible. Drugs should be given on the same dosage schedules whenever possible, and the administration should correspond to a daily routine in order to enhance the consistency of taking the drugs and compliance. For many drugs, once-daily dosing is available and should be prescribed when clinically appropriate. Relatives or other caregivers should be instructed in the drug regimen, and they, as well as others (e.g., home health aides and pharmacists), should be enlisted to help the older patient comply. Specially designed pill dispensers, dosage calendars, and other innovative techniques can be useful. Geriatric patients and their health care providers should keep an updated record of the drug regimen (see Fig. 14-2). Medications should be brought to appointments, and patients and families should show all medications to their physicians, particularly on initial visits to new primary care physicians or at a consultation with a specialist. Health care professionals should regularly inquire about other medications being taken (prescribed by other physicians or purchased over the counter) and review their patients' knowledge of and compliance with the drug regimen.

TABLE 14-1 STRATEGIES TO IMPROVE COMPLIANCE IN THE GERIATRIC POPULATION

  1. Making drug regimens and instructions as simple as possible.
    1. Use the same dosage schedule whenever feasible (e.g., once or twice per day)
    2. Time the doses in conjunction with a daily routine.
  2. Instruct relatives and caregivers on the drug regimen.
  3. Enlist others (e.g., home health aides, pharmacists) to help ensure compliance.
  4. Make sure the older patient can get to a pharmacist (or vice versa), can afford the prescriptions, and can open the container.
  5. Use aids (such as special pillboxes and drug calendars) whenever appropriate.
  6. Keep updated medication records (see Fig. 14-2).
  7. Review knowledge of and compliance with drug regimens regularly.

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ADVERSE DRUG REACTIONS AND INTERACTIONS

Primum non nocere ( first, do no harm ), a watchword phrase in the practice of medicine, is nowhere more applicable than when drugs are being prescribed for the geriatric population. Adverse drug reactions are the most common forms of iatrogenic illness (see Chap. 5). The incidence of adverse drug reactions in hospitalized patients increases from approximately 10 percent in those between 40 and 50 years of age to 25 percent in those older than age 80 (Lazarou et al., 1998). They account for between 3 and 10 percent of hospital admissions of older patients each year, and result in several billion dollars in yearly health care expenditures. Many drugs can produce distressing, and sometimes disabling or life-threatening, adverse reactions (Table 14-2). Psychotropic drugs and cardiovascular agents are common causes of serious adverse reactions in the geriatric population. In part, this is because of the narrow therapeutic:toxic ratio of many of these drugs. In some instances, age-related changes in pharmacology, such as diminished renal excretion and prolonged duration of action, predispose to adverse reactions. Some side effects can have a therapeutic benefit and may be key factors in drug selection (see below).

TABLE 14-2 EXAMPLES OF COMMON AND POTENTIALLY SERIOUS ADVERSE DRUG REACTIONS IN THE GERIATRIC POPULATION

DRUG COMMON ADVERSE REACTIONS
ANALGESICS (SEE Chap. 10)
Antiinflammatory agents Gastric irritation and ulcers
Chronic blood loss
Narcotics Constipation
ANTIMICROBIALS
Aminoglycosides Renal failure
Hearing loss
ANTIPARKINSONIAN DRUGS (SEE CHAP. 10)
Dopaminergic agents Nausea
Delirium
Hallucinations
Postural hypotension
Anticholinergics Dry mouth
Constipation
Urinary retention
Delirium
CARDIOVASCULAR DRUGS (SEE CHAP. 11)
Angiotensin-converting enzyme (ACE) inhibitors Cough
Impaired renal function
Antiarrhythmics Diarrhea (quinidine)
Urinary retention (disopyramide)
Anticoagulants Bleeding complications
Antihypertensives Hypotension
Sedation and/or other changes in mental function
Calcium-channel blockers Decreased myocardial contractility
Edema
Constipation
Diuretics Dehydration
Hyponatremia
Hypokalemia
Incontinence
Digoxin Arrhythmias
Nausea
Anorexia
Nitrates Hypotension
HYPOGLYCEMIC AGENTS
Insulin Hypoglycemia
Oral agents
PSYCHOTROPIC DRUGS (SEE Tables 14-9, 10 and 11)
Antidepressants (See Chap. 7)
Antipsychotics Sedation
Hypotension
Extrapyramidal movement disorders
Lithium Weakness
Tremor
Nausea
Delirium
Sedative and hypnotic agents Excessive sedation
Delirium
Gait disturbances and falls
OTHERS
Alendronate, risedronate Esophageal ulceration
Aminophylline, theophylline Gastric irritation
Tachyarrhythmias
Carbamazepine Anemia
Hyponatremia
Neutropenia
Cimetidine Mental status changes
Terbutaline Tremor

Because symptoms can be nonspecific or may mimic other illnesses, adverse drug reactions may be ignored or unrecognized. Patients and family members should be educated to recognize and report common and potentially serious adverse reactions. In some instances, another drug is prescribed to treat these symptoms, thus contributing to polypharmacy and increasing the likelihood of an adverse drug interaction. The problem of polypharmacy is exacerbated by visits to multiple physicians who may prescribe still more drugs and the use of multiple pharmacies. Medication records kept by the patient (see Fig. 14-2), as well as the physician's medical record, should help to prevent unnecessary polypharmacy when many physicians are involved. Several drugs commonly prescribed for the geriatric population can interact, with adverse consequences (Table 14-3). The more common types of potential adverse drug interactions are drug displacement from protein-binding sites by other highly protein-bound drugs, induction or suppression of the metabolism of other drugs, and additive effects of different drugs on blood pressure and mental function (mood, level of consciousness, etc.). In addition to the potential to interact with other drugs, several drugs can interact adversely with underlying medical conditions in the geriatric population, creating drug patient interactions (Table 14-4). A good example of this problem is the increased risk of hospitalization for congestive heart failure among older patients taking diuretics who are told to take a nonsteroidal antiinflammatory drug (Heerdink et al., 1998).

TABLE 14-3 EXAMPLES OF POTENTIALLY CLINICALLY IMPORTANT DRUG DRUG INTERACTIONS

INTERACTION EXAMPLES POTENTIAL EFFECTS
Interference with drug absorption Antacids interacting with digoxin, INH, antipsychotics
Enteral tube feedings and liquid phenytoin
Iron and ciprofloxacin
Diminished drug effectiveness
Displacement from binding proteins Warfarin, oral hypoglycemics, aspirin, chloral hydrate, other highly protein-bound drugs (see Table 14-6) Enhanced effects and increased risk of toxicity
Altered distribution Digoxin and quinidine Increased risk of toxicity
Altered metabolism Antifungals, erythromycin, clarithromycin SSRIs, with antihistamines, calcium-channel blockers, others* Decreased metabolism, increased levels of toxicity
Altered excretion Lithium and diuretics Increased risk of toxicity and electrolyte imbalance
Pharmacological antagonism Levodopa and clonidine Decreased antiparkinsonian effects
Pharmacological synergism Tricyclic antidepressants and antihypertensives Increased risk of hypotension
* See text.
Abbreviations: INH = isonicotine hydrazine; SSRI = selective serotonin reuptake inhibitor.

TABLE 14-4 EXAMPLES OF POTENTIALLY CLINICALLY IMPORTANT DRUG PATIENT INTERACTIONS

DRUG PATIENT FACTORS CLINICAL IMPLICATIONS
Diuretics Diabetes
Poor nutritional status
Decreased glucose tolerance
Increased risk of dehydration and electrolyte imbalance
Urinary frequency, urgency Incontinence may result
Angiotensin-converting enzyme (ACE) inhibitors
Beta blockers
Renovascular disease (severe)
Stress incontinence
Diabetes
Chronic obstructive lung disease
Congestive heart failure (CHF)
Peripheral vascular disease
Worsening renal function
Precipitate incontinence (cough)
Sympathetic response to hypoglycemia may be masked
Increased bronchospasm
Decreased myocardial contractility
Increased claudication
Narcotic analgesics Chronic constipation Worsening symptoms, fecal impaction
Tricyclic antidepressants CHF, angina Tachycardia, decreased myocardial contractility, postural hypotension exacerbating cardiovascular conditions
Tricyclic antidepressants, antihistamines, and other drugs with anticholinergic effects Constipation, glaucoma, and other visual impairments, prostatic hyperplasia, reflux esophagitis Worsening of symptoms
Antipsychotics Parkinsonism Worsening of immobility
Psychotropics Dementia Further impairment of cognitive function
Nonsteroidal antiinflammatory drugs CHF, on diuretics Increased risk of exacerbation of CHF

Health care professionals should have a thorough knowledge of the more common drug side effects, adverse reactions to drugs, and potential drug interactions

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in the geriatric population. Electronic databases available on the World Wide Web or on personal digital assistants (PDAs) can be helpful in this regard. Careful questioning about side effects should be an important part of reviewing the drug regimen at each visit. Many institutions use computers to detect potential adverse drug interactions and to prevent their occurrence. Software programs are now available that can assist in identifying potential adverse drug interactions. Special attention should be given to the potential for any newly prescribed drug to interact with drugs already being taken or with underlying medical or psychological conditions.

AGING AND PHARMACOLOGY

Several age-related biological and physiological changes are relevant to drug pharmacology (Table 14-5). With the exception of changes in renal function, however, the effects of these age-related changes on dosages of specific drugs for individual patients are variable and difficult to predict. In general, an understanding of the physiological status of each patient (taking into account factors such as state of hydration, nutrition, and cardiac output) and how that status affects the pharmacology of a particular drug is more important to clinical efficacy than are age-related changes. New technology in drug delivery systems, such as oral sustained-release preparations and skin patches, have been developed for many medications. Such technology may be useful in designing strategies to account for the effect of aging changes on pharmacology and to make many drugs safer in the geriatric population. Given these caveats, the effects of aging on each pharmacological process are briefly discussed below.

TABLE 14-5 AGE-RELATED CHANGES RELEVANT TO DRUG PHARMACOLOGY

PHARMACOLOGICAL PARAMETER AGE-RELATED CHANGES
Absorption Decreases in
   Absorptive surface
   Splanchnic blood flow
Increased gastric pH
Altered gastrointestinal motility
Distribution Decreases in
   Total body water
   Lean body mass
   Serum albumin
Increased fat
Altered protein binding
Metabolism Decreases in
   Liver blood flow
   Enzyme activity
   Enzyme inducibility
Excretion Decreases in
   Renal blood flow
   Glomerular filtration rate
   Tubular secretory function
Tissue sensitivity Alterations in
   Receptor number
   Receptor affinity
   Second-messenger function
   Cellular and nuclear responses

Absorption

Several age-related changes can affect drug absorption (see Table 14-5). Most studies, however, have failed to document any clinically meaningful alterations in drug absorption with increasing age. Absorption, therefore, appears to be the pharmacological parameter least affected by increasing age.

Distribution

In contrast to absorption, clinically meaningful changes in drug distribution can occur with increasing age. Serum albumin, the major drug-binding protein, tends to decline, especially in hospitalized patients. Although the decline is numerically small, it can substantially increase the amount of free drug available for action. This effect is of particular relevance for highly protein-bound drugs,

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especially when they are used simultaneously and compete for protein-binding sites (see Table 14-3).

Age-related changes in body composition can prominently affect pharmacology by altering the volume of distribution (Vd). The elimination half-life of a drug varies with the ratio Vd:drug clearance. Thus, even if the rate of clearance of a drug is unchanged with age, changes in Vd can affect a drug's half-life and duration of action.

Because total body water and lean body mass decline with increasing age, drugs that distribute in these body compartments, such as most antimicrobial agents, digoxin, lithium, and alcohol, may have a lower Vd and can, therefore,

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achieve higher concentrations from given amounts of drugs. On the other hand, drugs that distribute in body fat, such as many of the psychotropic agents, have a large Vd in the geriatric patients. The larger Vd will thus cause a prolongation of the half-life unless the clearance increases proportionately, which is unlikely to happen with increasing age.

Metabolism

The effects of aging on drug metabolism are complex and difficult to predict. They depend on the precise pathway of drug metabolism in the liver and on several other factors, such as gender and amount of smoking. There is evidence that the first, or preparative, phase of drug metabolism, including oxidations, reductions, and hydrolyses, declines with increasing age, and that the decline is more prominent in men than in women. In contrast, the second phase of drug metabolism (biotransformation, including acetylation and glucuronidation) appears to be less affected by age. There is also evidence that the ability of environmental factors (most importantly smoking) to induce drug-metabolizing enzymes declines with age. Even when liver function is obviously impaired, as by intrinsic liver disease or right-sided congestive heart failure, the effects of aging on the metabolism of specific drugs cannot be precisely predicted. It is not safe to assume, however, that geriatric patients with normal liver function tests can metabolize drugs as efficiently as can younger individuals.

The cytochrome P450 system in the liver has been extensively studied. More than 30 isoenzymes have been identified and classified into families and subfamilies. Genetic mutations in some of these enzymes, while relatively uncommon, can impair metabolism of specific drugs. Although aging may affect this system, the effects of commonly used drugs are probably more important. Ketoconazole, erythromycin, and the selective serotonin reuptake inhibitors (especially fluoxetine) can inhibit the metabolism of several drugs (see Chap. 7). Potentially fatal ventricular arrhythmias have been caused by high levels of the antihistamines terfenadine and astemizole, resulting from inhibition of these enzymes.

Excretion

Unlike those of metabolism, the effects of aging on renal functions are somewhat more predictable. The tendency for renal function to decline with increasing age can affect the pharmacokinetics of several drugs (and their active metabolites) that are eliminated predominantly by the kidney (Table 14-6). These drugs are cleared from the body more slowly, their half-lives (and duration of action) are prolonged, and there is a tendency to accumulate to higher (and potentially toxic) drug concentrations in the steady state.

TABLE 14-6 IMPORTANT CONSIDERATIONS IN GERIATRIC PRESCRIBING

DRUG MAJOR ROUTE OF ELIMINATION OTHER PHARMACOLOGICAL CONSIDERATIONS OTHER CONSIDERATIONS
ANALGESICS (SEE CHAP. 10)
Nonnarcotic
   Acetaminophen Hepatic No substantial age-related change in kinetics
Liver toxicity may occur in high doses
Analgesic effects of noninflammatory condition similar to aspirin and other antiinflammatory agents
   Aspirin Renal Highly protein- bound
Half-life may be prolonged at higher dosages
Enteric-coated preparations useful
   Nonsteroidal antiinflammatory agents Renal (naproxen, ibuprofen)
Hepatic (indomethacin)
Highly protein-bound (See Chap. 10)
   Cyclooxygenase-2 (COX-2) inhibitors Mixed    
Narcotic Hepatic Blood levels may be higher, pain relief longer Lower doses generally effective for analgesia
Constipation a major problem
ANTIMICROBIALS
Antibacterial
   Aminoglycosides (gentamicin, tobramycin, amikacin) Renal Half-life prolonged Nephrotoxicity and ototoxicity are major problems
Blood levels important
   Aztreonam Renal Half-life prolonged  
   Cephalosporins Renal Half-life prolonged  
   Clindamycin Hepatic    
   Erythromycin Hepatic    
   Quinolones Renal, hepatic Relatively long half-life allows twice a day dosage Can increase warfarin effects
   Penicillins Renal
Hepatic (nafcillin, cloxacillin)
Half-life prolonged
Highly protein-bound (nafcillin, cloxacillin, oxacillin)
Carbenicillin and ticarcillin high parenteral doses give a large sodium load
   Sulfonamides Renal Highly protein-bound Increased effects of warfarin
   Tetracyclines Renal
Hepatic (doxycycline)
Half-life prolonged  
   Vancomycin Renal Half-life prolonged Ototoxicity, nephrotoxicity
Blood levels important
Poor oral absorption makes oral preparation useful for Clostridium difficile associated diarrhea
Antitubercular
   Ethambutol Renal    
   Isoniazid Hepatic Genetic variation in rate of metabolism; no substantial age-related change Hepatotoxicity increases with age
   Rifampin Hepatic    
Antifungal
   Amphotericin Nonrenal   Nephrotoxicity a major problem
ANTIPARKINSONIAN AGENTS (SEE CHAP. 10)
Amantadine Renal    
Bromocriptine Hepatic    
Carbidopa-levodopa Hepatic   Cardiovascular toxicity increased
Entacapone, tolcapone Hepatic    
Pergolide Hepatic   Postural hypotension may occur
Pramipexole Renal    
Ropinirole Hepatic   Hallucinations relatively common at higher doses
Trihexyphenidyl Nonrenal    
CARDIOVASCULAR DRUGS (SEE CHAP. 11)
Antiarrhythmic
   Disopyramide Renal, hepatic   Can cause urinary retention
   Encainide Hepatic    
   Lidocaine Hepatic Volume of distribution increased
Half-life prolonged
Clearance unchanged
Blood levels helpful
Procainamide Renal Clearance decreased
Steady-state levels higher
Blood levels helpful
Quinidine Nonrenal Highly protein-bound
Clearance decreased
Half-life prolonged
Blood levels helpful
Tocainide Renal, hepatic    
Verapamil Hepatic Clearance decreased Pharmacological effects more pronounced and prolonged Interacts with and raises digoxin blood levels
Anticoagulant
   Heparin Nonrenal    
   Sulfinpyrazone Renal    
   Warfarin Hepatic Highly protein-bound
Sensitivity to effects increased
Multiple drug interactions
Antihypertensives     See Chap. 11 for more detailed discussion of antihypertensive therapy
   Atenolol Renal    
   Captopril Renal    
   Clonidine Renal    
   Diltiazem Hepatic Clearance decreased Use carefully with sinus node dysfunction
   Enalapril/lisinopril Renal Pharmacological effects more pronounced and prolonged  
   Hydralazine Hepatic Highly protein-bound  
   Metoprolol Hepatic Blood levels higher  
   Methyldopa Renal    
   Nadolol Renal    
   Nifedipine Hepatic    
   Propranolol Hepatic Highly protein-bound
Blood levels higher
Clearance decreased
Half-life prolonged
Sensitivity to effects decreased
 
   Prazosin Hepatic Highly protein-bound  
   Terazosin Renal, hepatic Highly protein-bound  
Diuretics
   Furosemide Renal Highly protein-bound Older patients predisposed to dehydration and electrolyte imbalance
Thiazides Renal   Potassium supplementation not always necessary
   Triamterene Hepatic   Glucose intolerance or diabetes may worsen
Digoxin Renal (15 40 % nonrenal) Decreased clearance
Half-life prolonged
Many with heart failure and sinus rhythm may not need digoxin (see Chap. 11)
HYPOGLYCEMIC AGENTS (SEE CHAP. 12)
Oral
   Acetohexamide Renal, hepatic Highly protein-bound (all oral hypoglycemics) See Chap. 12 for more detailed discussion of hypoglycemic therapy in the elderly
   Glipizide Hepatic    
   Glyburide Hepatic    
   Metformin Renal   May cause lactic acidosis
Must be withheld 48 h before and after iodinated contrast media
   Pioglidazone, rosiglitazone Hepatic    
   Tolazamide Hepatic    
   Tolbutamide Hepatic    
   Troglitazone Hepatic   Serum transminase monitoring suggested
Insulin Renal, hepatic Renal metabolism may be decreased
Sensitivity to effects may be decreased
 
PSYCHOTROPIC DRUGS (SEE Tables 14-9, 10 and 11)
Antidepressants (tricyclic, tetracyclic) Hepatic Highly protein-bound
Blood levels may be higher
See Chap. 7 for more detailed discussion on antidepressant drugs
Selective serotonin reuptake inhibitors (SSRIs) Hepatic Can inhibit cytochrome P450 isoenzymes May cause inappropriate antidiuretic hormone secretion and hyponatremia
Lithium Renal Clearance decreased Blood levels important
Antipsychotics Hepatic Highly protein-bound See Tables 14-9 and 14-11
Sedatives and hypnotics
   Benzodiazepines Hepatic
Renal (oxazepam)
Highly protein-bound
Diazepam half-life prolonged
See Tables 14-10 and 14-11
   Chloral hydrate Hepatic Highly protein-bound  
   Diphenhydramine Hepatic   Anticholinergic side effects may be a problem
PSYCHOTROPIC DRUGS
Zolpidem Hepatic Highly protein-bound  
OTHER DRUGS
Aminophylline, theophylline Hepatic Half-life prolonged Lower doses may give therapeutic blood levels
Blood levels helpful
Carbamazepine Hepatic Highly protein bound Several drugs can affect metabolism
Blood levels helpful
Cimetidine Renal Half-life prolonged
Steady-state blood levels higher
Can cause mental changes at high doses
Famotidine Renal, hepatic    
Gabapentin Renal Clearance decreased  
Nizatidine Renal    
Oxybutynin Hepatic   Prominent anticholinergic effects
Phenytoin Hepatic   Blood levels helpful
Low albumin results in higher free drug than levels indicate
Prophylthiouracil Hepatic, renal    
Raloxifene Hepatic   Increased risk of thromboembolism
Ranitidine Renal    
Sildenafil Hepatic Half-life prolonged  
Terbutaline Hepatic    
Thyroxine Hepatic Clearance decreased Maintenance dose lower
Effects can be monitored by thyroid-stimulating hormone blood levels (see Chap. 12)
Tolterodine Hepatic Blood levels higher Can have anticholinergic effects

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Several considerations are important in determining the effects of age on renal function and drug elimination:

  • There is wide interindividual variation in the rate of decline of renal function with increasing age. Thus, although renal function is said to decline by 50 percent between the ages of 20 and 90 years, this is an average decline. A 90-year-old individual may not have a creatinine clearance of only 50 percent of normal. Applying average declines to individual elderly patients can result in over- or underdosing.

  • Muscle mass declines with age; therefore, daily endogenous creatinine production declines. Because of this decline in creatinine production, serum creatinine may be normal at a time when renal function is substantially reduced. Serum creatinine, therefore, does not reflect renal function as accurately in elderly people as it does in younger persons.

  • A number of factors can affect renal clearance of drugs and are often at least as important as age-related changes. State of hydration, cardiac output, and intrinsic renal disease should be considered in addition to age-related changes in renal function.

Several formulas and nomograms have been used to estimate renal function in relation to age. Table 14-7 shows the most widely used and accepted formula. This formula is useful in initial estimations of creatinine clearance for the purpose of drug dosing in the geriatric population. Clinical factors (such as state of hydration and cardiac output), which vary over time, should be considered in determining drug dosages.

TABLE 14-7 RENAL FUNCTION IN RELATION TO AGE*

equation
* Several other factors can influence creatinine clearance (see text).
Source: From Cockcroft and Gault, 1976, with permission.

When drugs with narrow therapeutic:toxic ratios are being used, actual measurements of creatinine clearance and drug blood levels (when available) should be used.

Tissue Sensitivity

A proportion of the drug or its active metabolite will eventually reach its site of action. Age-related changes at this point that is, responsiveness to given drug

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concentrations (without regard to pharmacokinetic changes) are termed pharmacodynamic changes. Older persons are often said to be more sensitive to the effects of drugs. For some drugs, this appears to be true. For others, however, sensitivity to drug effects may decrease rather than increase with age. For example, older persons may be more sensitive to the sedative effects of given blood levels of benzodiazepines but less sensitive to the effects of drugs mediated by -adrenergic receptors. There are several possible explanations for these changes (see Table 14-5). The effects of age-related pharmacodynamic changes on dosages of specific drugs for individual geriatric patients remain largely unknown.

GERIATRIC PRESCRIBING

General Principles

Several considerations make the development of specific recommendations for geriatric drug prescribing very difficult. These include the following:

  • Multiple interacting factors influence age-related changes in drug pharmacology.

  • There is wide interindividual variation in the rate of age-related changes in physiological parameters that affect drug pharmacology. Thus, precise predictions for individual older persons are difficult to make.

  • The clinical status of each patient (including such factors as state of nutrition and hydration, cardiac output, intrinsic renal and liver disease) must be considered in addition to the effects of aging.

  • As more research studies with newer drugs are carried out in well-defined groups of older subjects, more specific recommendations will be possible.

Adherence to several general principles can make drug therapy in the geriatric population safer and more effective (Table 14-8). Cardiovascular drugs, which account for a substantial proportion of adverse drug reactions, are also discussed in Chap. 10. Because psychotropic drugs are so commonly used, they are discussed in greater detail below.

TABLE 14-8 GENERAL RECOMMENDATIONS FOR GERIATRIC PRESCRIBING

  1. Evaluate geriatric patients thoroughly in order to identify all conditions that could (a) benefit from drug treatment; (b) be adversely affected by drug treatment; (c) influence the efficacy of drug treatment.
  2. Manage medical conditions without drugs as often as possible.
  3. Know the pharmacology of the drug(s) being prescribed.
  4. Consider how the clinical status of each patient could influence the pharmacology of the drug(s).
  5. Avoid potential adverse drug interactions.
  6. For drugs or their active metabolites eliminated predominantly by the kidney, use a formula or nomogram to approximate age-related changes in renal function and adjust dosages accordingly.
  7. If there is a question about drug dosage, start with smaller doses and increase gradually.
  8. Drug blood concentrations can be helpful in monitoring several potentially toxic drugs used frequently in the geriatric population.
  9. Help to ensure compliance by paying attention to impaired intellectual function, diminished hearing, and poor vision when instructing patients and labeling prescriptions (and by using other techniques listed in Table 14-1).
  10. Monitor older patients frequently for compliance, drug effects, and toxicity.

GERIATRIC PSYCHOPHARMACOLOGY

Psychotropic drugs can be broadly categorized as antidepressants (discussed in detail in Chap. 7), antipsychotics (Table 14-9), and sedatives and hypnotics (Table 14-10). These drugs are probably the most misused class of drugs in the geriatric population. Several studies show that more than half of nursing home residents are prescribed at least one psychotropic drug and that these prescriptions are changed

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frequently. Ironically, there is also evidence that antidepressants may be underused in nursing homes, where there is a high prevalence of depression. Other studies suggest that psychotropic drugs are commonly prescribed inappropriately in the nursing home setting. This is of special concern because of the frequency of adverse reactions to these drugs. Federal rules and regulations contained in the Omnibus Budget Reconciliation Act of 1987 (OBRA 1987) contained specific guidelines on the use of psychotropic drugs in nursing homes. The OBRA 1987 guidelines are discussed in detail elsewhere (Ouslander et al., 1997) and are currently being updated (as of June 2003). These guidelines emphasize avoiding the use of frequent as needed dosing for nonspecific symptoms (e.g., agitation, wandering) and the inappropriate use of these drugs as chemical restraints. The appropriate use of antipsychotics for psychosis and several behavioral symptoms associated with dementia must, however, be distinguished from their use as chemical restraints.

TABLE 14-9 EXAMPLES OF ANTIPSYCHOTIC DRUGS*

DRUG APPROXIMATE EQUIVALENT DOSE (MG) GERIATRIC DAILY DOSE RANGE (MG) RELATIVE SEDATION POTENTIAL FOR SIDE EFFECTS
HYPOTENSION EXTRAPYRAMIDAL EFFECTS
Chlorpromazine (Thorazine, others) 100 10 300 Very high High Moderate
Haloperidol (Haldol) 2 0.25 6 Low Low Very high
Olanzapine (Zyprexa) 2.5 10 Low Low Low
Quetiapine (Seroquel) 12.5 200 Low Low Low
Risperidone (Risperdal) 0.25 8 Low Low Low
Thioridazine (Mellaril) 100 10 300 High Moderate Low
Thiothixene (Navane) 5 1 5 Low Low Very high
Ziprasidone (Geodon) 80 20 40 Low Moderate Low
* Other agents are also available.
Rigidity, bradykinesia, tremor, akathisia.
Not available.
Geriatric dosage ranges not well studied.

Several considerations can be helpful in preventing the misuse of psychotropic drugs in the geriatric population:

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  • Psychological symptoms (depression, anxiety, agitation, insomnia, paranoia, disruptive behavior) are often caused or exacerbated by medical conditions in geriatric patients. A thorough medical evaluation should therefore be done before symptoms are attributed to psychiatric conditions alone and psychotropic drugs are prescribed.

  • Reports of psychiatric symptomatology such as agitation are often presented to physicians by family caregivers and nursing home personnel who are inexperienced in the description, interpretation, and differential diagnosis of these symptoms. Agitation or disruptive behavior may, in fact, have been a reasonable response to an inappropriate interaction or situation created by the caregiver. Psychotropic drugs should, therefore, be prescribed only after the physician has clarified what the symptoms are and what correctable factors might have precipitated them.

  • Psychological symptoms and signs, like physical symptoms and signs, can be nonspecific in the geriatric patient. Therefore, appropriate drug treatment often depends on an accurate psychiatric diagnosis. Psychiatrists and psychologists experienced with geriatric patients should be consulted, when available, in order to identify and help target psychotropic drug treatment to the major psychiatric problem(s).

  • Many nonpharmacological treatment modalities can either replace or be used in conjunction with psychotropic drugs in managing psychological symptoms. Behavioral modification, environmental manipulation, supportive psychotherapy, group therapy, recreational activities, and other related techniques can be useful in eliminating or diminishing the need for drug treatment.

  • Within each broad category of psychotropic drug, there are considerable differences among individual agents with regard to effects, side effects, and potential interactions with other drugs and medical conditions. Rational prescription of these drugs necessitates careful consideration of the characteristics of each drug in relation to the individual patient.

  • Because geriatric patients are, in general, more sensitive to the effects and side effects of psychotropic drugs, initial doses should be lower, increases should be gradual, and monitoring should be frequent.

  • Careful, ongoing assessment of the response of target symptoms and behaviors to psychotropic drugs is essential. In addition to reports from patients themselves, objective observations by trained and experienced professionals should be continuously evaluated in order to adjust psychotropic drug therapy.

All psychotropic drugs must be used judiciously in geriatric patients because of their potential side effects. The most common and potentially disabling side effects of psychotropic drugs fall into four general categories: changes in cognitive status (e.g., sedation, delirium, dementia) and extrapyramidal, anticholinergic, and cardiovascular effects. Research documents that psychotropic drugs can

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contribute to cognitive impairment (Larson et al., 1987) and are associated with hip fractures in the geriatric population (Ray et al., 1987).

Anticholinergic and cardiovascular side effects are most prominent with the tricyclic antidepressants. Antipsychotic drugs with -adrenergic blocking properties, including chlorpromazine and thioridazine, also have cardiovascular side effects, most notably hypotension. Newer drugs without such effects have largely replaced these agents. Extrapyramidal side effects are most common with several antipsychotic drugs (see Table 14-9). These effects which include pseudoparkinsonism (rigidity, bradykinesia, tremor), akathisia (restlessness), and involuntary dystonic movements (such as tardive dyskinesia) can be severe and may cause substantial disability. Rigidity and bradykinesia can lead to immobility and the complications discussed in Chap. 10. Akathisia can make the patient appear more anxious and agitated, and can lead to the inappropriate prescription of more medication. Tardive dyskinesia can cause permanent disability as a consequence of continuous orolingual movements and difficulty with eating. In addition to side effects, many psychotropic drugs interact with each other and with other drug classes. Some of these interactions can be clinically important and can enhance the risk of toxicity (Steffens and Krishnan, 1998).

Optimal efficacy of psychotropic drugs necessitates considering the characteristics of the drugs in relation to several clinical factors in each patient (Table 14-11). In general, the antipsychotic agents should be reserved for treatment of psychoses (i.e., paranoid states, delusions, and hallucinations), which are common in dementia patients. These drugs may also be useful for severe physical and/or verbal agitation that does not respond to nonpharmacological interventions. Environmental and behavioral interventions should be attempted before psychotropic drugs are prescribed. There is no clear choice of one antipsychotic agent over another based on controlled clinical trials. Some of the newer agents, such as risperidone, olanzapine, and quetiapine, have less extrapyramidal side effects than older drugs. They are clearly the drugs of choice for psychosis that occurs in dementia of Parkinson's disease and dementia associated with Lewy bodies (see Chap. 6). In some situations, intermittent agitation, especially at night, is best treated by a short-acting benzodiazepine (see Table 14-10). When antipsychotics fail or cause side effects, and sedation is not desired, carbamazepine and valproic acid may be useful alternatives in some patients. Both of these drugs, however, have the potential for hematological and hepatic toxicity and must be used cautiously in the geriatric population. Periodic attempts to taper and discontinue the use of these drugs are required in nursing facilities, and can result in the successful removal of psychotropics for some patients (Cohen Mansfield et al., 1999).

TABLE 14-11 CLINICAL CONSIDERATIONS IN PRESCRIBING PSYCHOTROPIC DRUGS

CLINICAL INDICATOR MOST USEFUL TYPES COMMENTS
Depression with psychomotor retardation Less sedating antidepressant (e.g., fluoxitene, paroxetine, sertraline) See Chap. 7
Depression with insomnia and/or weight loss Antidepressant with sedative and weight-gaining effects (e.g., mirtazapine)  
Agitation without psychosis that occurs at night Short-acting sedative (e.g., lorazepam) or a hypnotic (e.g., zolpidem, temazepam) Should generally be used on an as-needed basis
Nonpharmacologic intervention may be more appropriate
Psychoses without prominent agitation (e.g., delusions and hallucinations in patients with depression or dementia) Less sedating antipsychotic (e.g., risperidone, olanzapine) Extrapyramidal effects may occur
Risperidone may cause postural hypotension if not titrated slowly
Severe physical or verbal agitation poorly controlled by nonpharmacological intervention More sedating antipsychotic (e. g., quetiapine, thioridazine, loxapine) Akathisia can make patient appear more agitated
Insomnia Temazepam
Zolpidem
Underlying cause (s) should be sought; nonpharmacological interventions often helpful

TABLE 14-10 EXAMPLES OF SEDATIVES AND HYPNOTIC AGENT*

DRUG (BRAND NAME) GERIATRIC DAILY DOSE RANGE (MG) RELATIVE RAPIDITY OF EFFECT AFTER ORAL ADMINISTRATION HALF-LIFE(H) ACTIVE METABOLITES
BENZODIAZEPINES
Longer acting
  Clonazepam (Klonopin) 0.5 5 Intermediate 20 100 No
  Clorazepate (Tranxene) 7.5 15 Fast 50 100 Yes
  Diazepam (Valium) 1 5 Fast 40 200 Yes
  Flurazepam (Dalmane) 15 Fast 18 50 Yes
Shorter acting
  Alprazolam (Xanax) 0.25 0.75 Fast 2 5 No
  Estrazolam (ProSom) 0.5 2 Intermediate 10 24 No
  Lorazepam (Ativan) 1 2 Intermeidate 10 20 No
  Oxazepam (Serax) 10 30 Slow 5 15 No
  Temazepam (Restoril) 7.5 15 Fast 5 15 No
  Triazolam (Halcion) 0.0625 0.125 Intermediate 2 5 No
OTHERS
  Chloral hydrate (Noctec, etc.) 500 1500 Fast 7 10 Yes
  Buspirone (BuSpar) 10 30 Fast 2 3 Yes
  Zaleplon (Sonata) 10 Very fast 1 No
  Zolpidem (Ambien) 5 Very fast 2 3 No
* Several other agents are also available.
Longer-acting benzodiapines should be avoided in geriatric patients.
Must be used chronically to be an effective antianxiety agent.

A variety of nonpharmacological measures can be effective in geriatric patients with agitation or excessive anxiety. Specific behavioral and other nonpharmacological therapeutic approaches are described in detail in some of the

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suggested readings at the end of this chapter (see also Chap. 6). These measures, however, are often unavailable, impractical, inappropriate, or unsuccessful. Patients with severe impairment of cognitive function can be especially difficult to manage with nonpharmacological measures alone, particularly when their physical and/or verbal agitation is interfering with their care (or the care of others around them). Thus, drug treatment of agitation is necessary in these patients.

Insomnia, like agitation, can be the manifestation of depression or physical illness. It is a very common complaint in geriatric patients, and causes of sleep disorders should be sought (see Chap. 7). Nonpharmacological measures (such as increasing activity during the day, diminishing nighttime noise, and ensuring cooler nighttime temperatures) are sometimes helpful. Several alternatives are available for drug treatment of insomnia (see Table 14-10). Melatonin, a naturally occurring hormone available over the counter, has gained increasing popularity as a hypnotic. Geriatric sleep disturbances are associated with changes in the melatonin cycle. Doses of 1 to 3 mg may improve the initiation and maintenance of sleep. The long-term effects of chronic hypnotic use in the geriatric population are unknown, but rebound insomnia can become a problem in patients who use hypnotics (especially benzodiazepine hypnotics and melatonin) regularly and then discontinue them. Whatever the indication, it is extremely important that after a psychotropic drug is prescribed the patient be closely monitored for the effects of the drug on the target symptoms and side effects, and that the drug regimen be adjusted accordingly.

References

Cockcroft DW, Gault MH: Predictions of creatinine clearance from serum creatinine. Nephron 16:31 41, 1976.

Cohen-Mansfield J, Lipson S, Werner P, et al: Withdrawal of haloperidol, thioridazine, and lorazepam in the nursing home. Arch Intern Med 159:1733 1740, 1999.

Heerdink ER, Leufkens HG, Herings RMC, et al: NSAIDs associated with increased risk of congestive heart failure in elderly patients taking diuretics. Arch Intern Med 158:1108 1112, 1998.

Larson EB, Kukull WA, Buchner D, et al: Adverse drug reactions associated with global cognitive impairment in elderly persons. Ann Intern Med 107:169 173, 1987.

Lazarou J, Pomeranz BH, Corey PN: Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA 279:1200 1205, 1998.

Ouslander J, Morley J, Osterweil D: Medical Care in the Nursing Home, 2d ed. New York, McGraw-Hill, 1997.

Ray WA, Griffin MR, Schaffner W, et al: Psychotropic drug use and the risk of hip fracture. N Engl J Med 316:363 369, 1987.

Steffens DC, Krishnan KRR: Metabolism, bioavailability, and drug interactions. Clin Geriatr 14:17 32, 1998.

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Suggested Readings

Anonymous: Antimicrobial prophylaxis in surgery. Med Lett 39:97 102, 1997.

Anonymous: Drugs for psychiatric disorders. Med Lett 39:33 40, 1997.

Anonymous: Drugs that may cause psychiatric symptoms. Med Lett 44:59 62, 2002.

Beers MH: Explicit criteria for determining potentially inappropriate medication use by the elderly. Arch Intern Med 157:1531 1536, 1997.

Board of Directors of the American Association for Geriatric Psychiatry, Clinical Practice Committee of the American Geriatrics Society, and Committee on Long- Term Care and Treatment for the Elderly: Psychotherapeutic medications in the nursing home. J Am Geriatr Soc 40:946 949, 1992.

Carlson DL, Fleming KC, Smith GE, et al: Management of dementia-related behavioral disturbances: a nonpharmacologic approach. Mayo Clin Proc 70:1108 1115, 1995.

Mintzer JE, Hoernig KS, Mirski DF: Treatment of agitation in patients with dementia. Clin Geriatr Med 14:147 175, 1998.

Selma TP, Beizer JL, Higbee MD: Geriatric Dosage Handbook, 5th ed. Hudson, OH, American Pharmaceutical Association and Lexi-Comp, 2000 2001.



Essentials of Clinical Geriatrics
Understanding Thin Client/Server Computing (Strategic Technology Series)
ISBN: 71498222
EAN: 2147483647
Year: 2002
Pages: 23
Authors: Joel P Kanter

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