Use of antiarrhythmic drugs in elderly patients

Abstract

Human aging is a global issue with important implications for current and future incidence and prevalence of health conditions and disability. Cardiac arrhythmias, including atrial fibrillation, sudden cardiac death, and bradycardia requiring pacemaker placement, all increase exponentially after the age of 60. It is important to distinguish between the normal, physiological consequences of aging on cardiac electrophysiology and the abnormal, pathological alterations. The age-related cardiac changes include ventricular hypertrophy, senile amyloidosis, cardiac valvular degenerative changes and annular calcification, fibrous infiltration of the conduction system, and loss of natural pacemaker cells and these changes could have a profound effect on the development of arrhythmias. The age-related cardiac electrophysiological changes include up- and down-regulation of specific ion channel expression and intracellular Ca(2+) overload which promote the development of cardiac arrhythmias. As ion channels are the substrates of antiarrhythmic drugs, it follows that the pharmacokinetics and pharmacodynamics of these drugs will also change with age. Aging alters the absorption, distribution, metabolism, and elimination of antiarrhythmic drugs, so liver and kidney function must be monitored to avoid potential adverse drug effects, and antiarrhythmic dosing may need to be adjusted for age. Elderly patients are also more susceptible to the side effects of many antiarrhythmics, including bradycardia, orthostatic hypotension, urinary retention, and falls. Moreover, the choice of antiarrhythmic drugs in the elderly patient is frequently complicated by the presence of co-morbid conditions and by polypharmacy, and the astute physician must pay careful attention to potential drug-drug interactions. Finally, it is important to remember that the use of antiarrhythmic drugs in elderly patients must be individualized and tailored to each patient's physiology, disease processes, and medication regimen.

Keywords: aging; antiarrhythmic drugs; cardiac electrophysiology; ion channels; pharmacodynamics; pharmacokinetics; polypharmacy.

Figure 1.. World population by age and sex: 1950–2050. Distribution of the world population by age and sex from 1950 (top panel) to 2000 (middle panel) and 2050 (bottom panel). With global aging, the world population is being transformed from a population pyramid to a population dome. These changes occur not only in developed countries (grey) but also in developing countries (white). Adopted from United Nations and United States Census Bureau.,

Figure 2.. Age-related changes in pharmacokinetics of antiarrhythmic drugs. Diagrammatic representation of age-related changes in the absorption, distribution, metabolism, and elimination of antiarrhythmic drugs. GI: gastrointestinal; GFR: glomerular filtration rate; CrCl: creatinine clearance; ↔: unalter; ↑: increase; ↓: decrease.