Predicting and Preventing Adverse Drug Reactions in the Very Old

Abstract

The size of the elderly population has been increasing steadily for several years. Individuals in this age group often have several concomitant diseases that require treatment with multiple medications. These drugs, for various reasons and especially as a consequence of potential accumulation, may be associated with adverse reactions. Of the numerous factors that can favour the occurrence of these adverse drug reactions, the most important are the pathophysiological consequences of aging, particularly as these apply to the very old. Although absorption of drugs is not usually reduced in the elderly, diffusion, distribution and particularly elimination decline with age. Furthermore, while hepatic metabolic function is fairly normal, renal function is usually markedly depressed in very old individuals, and this can translate into clinical consequences if it is not taken into account. This is why, before administration of any drug in the elderly, evaluation of glomerular filtration rate is essential. Validated estimations such as those obtained from the classical Cockcroft-Gault formula or from more recent methodologies are required. In addition to reductions in various organ functions, factors connected with very old age such as frailty, falls, abnormal sensitivity to medications and polypathology, all of which tend to be more common in the last years of life, all directly impact on adverse drug reaction occurrence. Given these characteristics of the elderly population, the best way to reduce the prevalence of adverse drug reactions in this group is to limit drug prescription to essential medications, make sure that use of prescribed agents is clearly explained to the patient, give drugs for as short a period as possible, and periodically re-evaluate all use of drugs in the elderly.

Canadian Cardiovascular Society consensus conference recommendations on heart failure 2006: Diagnosis and management

“…Elderly patients are vulnerable to adverse drug events (ADEs) due to the growing complexity of medication regimens, age-related physiological changes and a higher burden of comorbid illnesses (142). Cardiovascular medications are frequently associated with ADEs in the elderly (143).…”

Pharmacokinetic Modifications and Drug-Drug Interactions in Clinical Monitoring of the Elderly: A Short Review

“…Moreover, some ions (e.g., calcium, iron), vitamins, and maybe some nucleoside derivatives and gabapentin, which utilize the active transport or facilitated diffusion to cross this epithelium, can be absorbed at a slower rate [12]. In general, however, the enteral absorption is not a critical factor in the onset of interactions [13].…”

“…In the latter case (e.g., benzodiazepines, tricyclic antidepressants, lidocaine, verapamil), the increase of V d can rise the elimination half-life (t½) of the drug, since this parameter is closely associated, and in direct proportion, to the V d [11,12]. Interestingly, the concomitant use of diuretics can reduce even more the extracellular fluid content, increasing the risk of toxicity [13]. Furthermore, the frail elderly with decreased weight has a decline in the percentage of body fat and increased V d even for lipid-soluble substances [13].…”

“…Interestingly, the concomitant use of diuretics can reduce even more the extracellular fluid content, increasing the risk of toxicity [13]. Furthermore, the frail elderly with decreased weight has a decline in the percentage of body fat and increased V d even for lipid-soluble substances [13].…”

“…While serum albumin may be reduced by up to 20%, α 1 -acid glycoprotein may increase [11][12][13][14]. However, these changes have no clinical relevance in general, as evidenced by Grandison and Boudinot in their excellent review [19], except when other conditions trigger/exacerbate such variations such as malnutrition and disease (e.g., cancer) and when the drug has a high rate of binding to these proteins (Box 1) and/or has a low therapeutic index [11,13].…”