Within the past decade, health professionals have expressed a growing concern regarding the amount of drug usage among our elderly population. Utilization studies reveal that more drugs are prescribed for the gerontic segment of society than for younger age groups. Both Rabin1 and Hurwitz2 concluded that significantly more patients of the over 60 age group were subjected to excessive amounts of prescribed drugs. Butler' noted that while elderly citizens (65 years and over) comprise only 11% of the United States population, they consume 25% of all prescribed medications. Zawadski, Glazer, and Lurie4 report that drug expenditures are more than twice as high for the aged than for the nonaged, with a disproportionately large expenditure for psychotropic drugs. Eisdorfer5 points out that psychotropic agents comprise a major proportion of all drugs prescribed in the United States.
The incidence of drug-induced i>ide effects and adverse reactions rises steadily with age and with the number of drugs prescribed.6 Specific physiological changes associated with increasing age maketheelderly client prone to having more, and more severe, drug mishaps.7 Such vulnerability demands that health professionals possess knowledge of the physiology of aging in order to provide effective care. Knowledge of the pharmacodynamic aspects of aging affecting psychotropic kinetics becomes especially cogent in the light of recent utilization studies.
Aging in the Body Systems
Aging, the progressive deterioration of an organism after maturation, is one of the most universal, inevitable, and conspicuous characteristics observable in nature. With the passage of time, changes occur in the properties, organization, or composition of all objects and living systems.8 Suehler defines aging as a universal, intrinsic, progressive, and deleterious process. Since the beginning of time, man has been trying to elucidate how and why the aging process occurs. Although a plethora of theories on the etiology of aging exists today, the primary cause of aging remains unsolved. However, researchers have accumulated a substantial body of knowledge describing the aging process itself. Numerous physiological changes are associated with the various body systems as they age. Many of these age-dependent changes are crucial variables affecting the absorption, distribution, metabolism, and excretion of drugs.
Cardiac output declines in a linear fashion with age. The cardiac output at 80 years of age is about half that at 20 years of age.10 Peripheral resistance and circulatory time increase, resulting in diminished cardiac reserve and regional blood flow. Cardiac output in the elderly is redistributed to the cerebral and coronary circulation at the expense of flow to the kidney, liver, and other organs." Decreased cardiac output and impaired circulation can delay or decrease drug distribution to target sites or organs of elimination.12
The villi of the mucosa of the small bowel change shape as they age, becoming shorter and broader. As a result, with increasing age, absorption of some substances is reduced, incomplete, or delayed.13 Decreased absorption of xylose14 and iron in elders may indicate some decrease in the efficiency of drug absorption. Richey and Bender15 indicate that abnormal gastric motility affects drug metabolism in two ways: (a) the rate at which drugs enter the circulation may be altered resulting in excessive or adverse physiological reactions, or (b) inadequate blood levels are achieved and a limited drug effect takes place. In addition, intestinal blood perfusion is reduced in the elderly by 40 to 50%. Bender16 maintains that depleted blood supply can decrease transfer of drugs across the serosal membrane.
With aging, there is a decrease in hepatic blood flow and the liver decreases in size.17 Kato and Tanaka!li reported age-related impairment of enzyme induction within the smooth endoplasmic reticulum of hepatic microsomes. The duration of action of many drugs is established by the rate at which they are metabolized by the hepatic microsomal enzymes, converted to other forms, and subsequently excreted. Blunted response to hepatic enzyme inducers occurring with age may significantly increase drug plasma levels, causing accumulation and intoxication.19
Diminution of kidney function with age has been well documented. Tubular cell functions decrease steadily with age. Renal blood flow and glomerular filtration rate decrease approximately 50% from age 40 to age 85.2U The kidney is the body's primary organ for drug excretion. Reduced glomerular filtration and renal blood flow in the elderly markedly decrease ihe rate of elimination of drugs excreted by the kidney. Decreased creatinine clearance in the elderly emphasizes the frequency with which cumulation and toxicity can occur.
With advancing age, the mechanism responsible for integrating the activity of organ systems becomes less effective. Finch21 reports age-related changes in brain metabolism with decreased conduction of nerve impulses. Thus, the integrative tasks of the central nervous system (CNS) become less efficient and decreasingly responsive. Consequently, the ageds' overall ability to adjust to stress is greatly diminished. Changes in homeostatic capability may influence elders overall response to a particular drug.
Psychotropic Drug Handling in the Aged
Various terms have been used to describe different classes of psychotropic drugs. Hollister" employs a simple approach to classifying psychoactive drugs by identifying them according to their areas of effectiveness: (a) antipsychotics, (b) antidepressives, (c) antimaníes, and (d) antianxiety agents.
Phenothiazine derivatives are the most frequently prescribed antipsychotic agents. Age-related physiological changes make the elderly client particularly prone to develop adverse reactions from this potent group of psychotropic drugs. The total effect of phenothiazines in the aged is the sum of the stimulation and inhibition of nerve cells in various parts of a brain in partial decline.23 The aged are particularly sensitive to cholinergic blockage that may aggravate constipation24 and cause xerostoma, possibly leading to parotid infections. In addition, the aged are especially prone to develop the acute neurotoxic side effects of phenothiazine agents. Older clients have a high incidence of parkinsonism-like reactions that are often permanent and unresponsive to antiparkinson drugs. Age-related CNS instability can cause older individuals to develop tardive dyskinesia, a more severe neurotoxic side effect of phenothiazines. Tar-dive dyskinesia is associated with involuntary buccal-facial-mandibular and buccal-lingual movements that may gradually progress to include movements of the limbs and trunk. The symptoms of tardive dyskinesia may become manifest only after reduction in the dosage of the medication, and may persist indefinitely.25 Compromised cardiac status makes the elderly client especially vulnerable to phenothiazine-induced hypotension, which may markedly exacerbate a confusional state.26 Other prominent side effects of phenothiazine therapy such as drowsiness, nasal congestion, dry mouth, and urinary retention, also occur with great frequency in the elderly client due primarily to diminished metabolic function.27
Depression in elderly clients is frequently treated with monamine oxidase inhibitors (MAO) or tri-cyclic derivatives. Adverse reactions of particular concern for older persons taking MAO inhibitors include hypotensive or hypertensive crisis, voiding problems, parkinsonlike tremors, and decreased amount of red blood cells.28 Elders experience an increased incidence of side effects from tricyclicantidepressants because of age-related cardiovascular and CNS changes. Adverse reactions frequently encountered by the aged include severe orthostatic hypotension and syncope, tremors, ataxia, and atropine-like effects. In addition, diminution of liver metabolism rates greatly increase the ageds' risk of developing glaucoma, urinary retention, constipation, and atropine-like delirium. Iatrogenic delirium is often mistaken for an increase in psychiatric symptoms and the dose of the offending agent is raised, further threatening the client.29
Lithium carbonate is often the drug of choice in recurrent depression or in manic-depressive disease. Poor renal clearance may increase the ageds' susceptibility to lithium toxicity. Symptoms of lithium toxicity including confusion, coarse tremor, slurred speech, choreo-athetoid movements, and vasopressinresistant syndromes similar to diabetes insipidus have been reported in elderly clients with therapeutic serum levels.30
Barbiturates are frequently used to control the symptoms of anxiety in elderly clients. Age-related decrements in renal function and hepatic-metabolism make the older client especially prone to experience dangerous side effects of barbiturates including drowsiness, ataxia, confusion, dizziness, blurred vision, headache, constipation, urinary retention, and hypotension. Researchers demonstrated that phénobarbital and amylobarbitone gave significantly higher plasma levels in an elderly group than in a 20-40-year-old group.31 Fine has demonstrated that barbiturates may produce different effects in the aged client, tending to stimulate rather than depress.
Responsibilities of Health Professionals
Evidence exists that aging may influence all phases of pharmacodynamics. Age-related alteration in the absorption, distribution, metabolism, and excretion of drugs augments the risk of drug-induced disease and mortality. Each member in the health care delivery system has a responsibility toward the client in the management of his drug therapy.33 Fulfilling this responsibility necessitates possession of knowledge regarding the involutional changes affecting drug handling in the aged. Prevention of medically induced hazards demands that health professionals come to grips with the variables affecting geriatric pharmacology.
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- 2. Hurwitz Ν: Predisposing factors in adverse reactions to drugs. Br Med J 1:536, 1969.
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