Principles of drug therapy in geriatric patients.

The elderly comprise 12 percent of the U.S. population but consume 33 percent of all prescription drugs. The incidence of adverse drug reactions is significantly higher in persons over age 65 than in younger population groups. The increased risk of adverse drug effects is related to decreased organ reserve capacity, to altered pharmacokinetics and pharmacodynamics, and to polypharmacy with associated drug-drug and drug-disease interactions. An organized therapeutic plan and critical evaluation of the list of drugs an elderly patient is taking will help in establishing a safe and effective drug regimen.

Alternative first-line therapies in geriatric hypertension.

Between 45 and 60% of elderly persons have mild to moderate hypertension. In those with combined systolic/diastolic hypertension, blood pressure reduction significantly reduces morbidity and mortality. Secondary causes of hypertension, particularly renovascular, should be considered in elderly patients with a recent history of hypertension. Because of their proven efficacy and low cost, low-dose thiazide diuretics remain an important first-line therapy. Angiotensin-converting enzyme (ACE) inhibitors and calcium-channel blocking agents have also been shown to be effective and well-tolerated in the elderly. Increased attention is being paid to adverse drug effects and to the overall effect of antihypertensive therapy on quality of life. ACE inhibitors are particularly attractive in the elderly due to their possibilities in this area. In the elderly, the combination of a low-dose thiazide diuretic with an ACE inhibitor enhances antihypertensive efficacy while blunting the adverse metabolic effects of the diuretic.

Digitalis glycosides.

The digitalis glycosides are potent cardiovascular drugs with a low therapeutic index and a high incidence of iatrogenic complications. Digoxin is the most commonly used preparation. Common indications include rate control in atrial fibrillation, as well as the treatment of other atrial tachyarrhythmias, and low-output congestive heart failure. Digitalis is contraindicated in idiopathic hypertrophic subaortic stenosis (unless atrial fibrillation is present) and in some patients with Wolff-Parkinson-White syndrome.

Hyperlipidemia.

Ten percent of the U.S. population has hyperlipidemia. The most commonly encountered phenotypes include Type IIa, Type IIb and Type IV. Anion-exchange resins are the drugs of choice for hypercholesterolemia, while gemfibrozil is the preferred agent for massive hypertriglyceridemia. Clofibrate is the drug of choice for the rare Type III hyperlipidemia. Successful management begins with evaluation of the total clinical picture, including genetic factors, measurement of cholesterol and triglycerides, and visual examination of the serum.

The effect of chlorpropamide hyponatremia on mental status in a nursing home population.

Fifty-nine nursing home patients (average age, 79.9 +/- .9 years) receiving chlorpropamide were screened with a serum sodium determination. Nine patients (15.3 percent) had a serum sodium concentration less than 135 mEq/L; six of these patients (10.2 percent) had a serum sodium equal to or less than 130 mEq/L; none of the patients had a serum sodium less than 125 mEq/L. Five hyponatremic patients (Na less than or equal to 130 mEq/L) and nine normonatremic patients (Na greater than or equal to 135 mEq/L) were screened with a standardized mental status examination and additional laboratory studies. The hyponatremic patients were switched to tolazamide after a one-week wash-out period, and the mental status examination and laboratory studies were repeated in both groups four weeks later. One patient in the hyponatremic group died during the course of the study; the other four became normonatremic on tolazamide. Mental status scores increased significantly in the hyponatremic group, 16.0 +/- 3.6 to 20 +/- 4.6 (a 37.3 +/- 21.5 percent increase), compared with the normonatremic group, 14.5 +/- 2.6 to 15.8 +/- 2.9 (a 7.8 +/- 3.2 percent increase). There were no significant differences in serum glucose, creatinine, chlorpropamide, or antidiuretic hormone concentrations between the two groups. It is recommended that periodic serum sodium determinations be obtained in geriatric patients receiving chlorpropamide.

Drug interactions.

Drug interactions have been implicated in approximately 7 percent of all reported adverse drug reactions. Although many drug interactions are not clinically significant, the potential for an interaction increases from 5.6 percent in patients receiving two drugs to 100 percent in patients receiving eight or more drugs. Drug interactions can involve alterations in the pharmacokinetic parameters of absorption, distribution, metabolism and excretion, or can result from cumulative or antagonistic effects.

Atrial fibrillation.

Although most cases of sustained atrial fibrillation are associated with mitral valve disease, hypertension, cardiac failure and atherosclerotic heart disease, some cases occur in the absence of any identifiable organic pathology. The consequences of atrial fibrillation include reduction in cardiac output, systemic emboli and an exaggerated ventricular response to exercise. In most clinical situations, digoxin is the drug of choice for controlling the ventricular response. Cardioversion should be undertaken in appropriately selected patients.

Hyperuricemia and gout.

Although chronic tophaceous gout has become increasingly uncommon, hyperuricemia and acute gout are still common clinical entities. Most patients with hyperuricemia are under-excreters, and many of these cases are drug induced. Since longstanding asymptomatic hyperuricemia does not appear to cause progressive renal insufficiency, and uric acid renal stones are uncommon in underexcreters, these patients generally require no treatment. The minority of patients who overproduce uric acid are at increased risk for urolithiasis, and therapy should be decided on an individual basis. Acute gout is best treated with colchicine or indomethacin. The newer non-steroidal anti-inflammatory drugs (ie, ibuprofen, sulindac) may prove to be equally effective and are associated with fewer gastrointestinal side effects. Prophylaxis should be undertaken in patients with recurrent gout or documented uric acid urolithiasis. Although uricosuric drugs appear to be less toxic than allopurinol, they should not be used in patients who overproduce uric acid or in patients who have a history of urolithiasis or renal insufficiency. The allopurinol hypersensitivity syndrome is being reported with increased frequency and may be fatal.

Geriatric drug therapy.

Elderly Americans make up 11 percent of the population but consume 25 percent of all prescription medications. The incidence of adverse drug effect is 1.5 to 3 times higher in older patients and accounts for numerous hospitalizations. The basic pharmacokinetic parameters of absorption, distribution, metabolism, and excretion are all significantly altered in geriatric patients. Certain specific drug side effects, such as orthostatic hypotension and anticholinergic effects, can be particularly hazardous in older patients. This paper describes general therapeutic principles for geriatric patients. Commonly used drug categories are considered separately. A thorough knowledge of these principles will allow the physician to prescribe drugs more effectively, improve patient compliance, and minimize adverse drug effects.

Antiplatelet therapy.

Much new information has been gleaned about the morphology, biochemistry and function of platelets. The pathophysiology of atherosclerosis and thromboembolic disorders appears to be related to abnormal platelet function. Endothelial damage, thromboxane A2, Thrombin, adenosine diphospate and epinephrine may each promote platelet aggregation, whereas prostacyclin impairs aggregation. Aspirin, sulfinpyrazone and dipyridamole have been used as antiplatelet agents, and specific indications are being developed to guide their selection.

Rational use of drug levels.

Considerable strides have been made in pharmacokinetics the last decade. Such techniques as gas chromatography and radioimmunoassay can measure minute quantities of drugs in serum and other body fluids. These assays are now available in many community hospitals. Therapeutic serum concentrations have been established for many drugs. Proper interpretation of serum drug levels permits precision in the use of drugs and minimizes adverse effects.