Understanding and preventing drug interactions in elderly patients

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

“…In theory, opioid and cholinergic antagonists, which tend to decrease gastric emptying and gastrointestinal transit, could more significantly restrict the absorption of other drugs in older subjects due to an already compromised basal motility [3,14]. Conversely, some reports show that the gastric emptying time at advanced age is not different from young adults [16].…”

“…For example, the elevation of gastric pH may promote the early dissolution of formulations in the stomach with enteric coating (gastro-resistant) and affect the integrity of the drug and its absorption, which may be augmented in the case of basic drugs. A pharmaceutical product designed to dissolve in the normal gastric pH may also not dissolve properly in a higher pH, which can lead to incomplete absorption of the drug [3,14]. O'Connor-Semmes et al [15] showed that in the presence of ranitidine, the AUC of triazolam was 10% higher in adults < 60 years old and 30% higher in those who were older than that.…”

“…CYP is a hemoprotein that presents several isoforms which differ in the inducibility and inhibitory pattern by certain substances, and probably also in the specificity of its catalytic action [19]. Among the CYP isoenzymes, the most commonly involved in drug biotransformation are CYP3A4, CYP2D6 (as a whole, these two are responsible for biotransformation of approximately 75% of all drugs), CYP1A2, CYP2C9, CYP2C19 and CYP2E1 [3]. Importantly, the activity and expression of the major isoform, CYP3A4, is dependent on normal liver function and is progressively decreased after its optimal performance in adulthood, reflecting the relative inability of biotransformation of older patients [3,11,21].…”

“…Among the CYP isoenzymes, the most commonly involved in drug biotransformation are CYP3A4, CYP2D6 (as a whole, these two are responsible for biotransformation of approximately 75% of all drugs), CYP1A2, CYP2C9, CYP2C19 and CYP2E1 [3]. Importantly, the activity and expression of the major isoform, CYP3A4, is dependent on normal liver function and is progressively decreased after its optimal performance in adulthood, reflecting the relative inability of biotransformation of older patients [3,11,21]. On the other hand, CYP2D6, which is responsible for ~25% of drug biotransformation, is particularly resistant to the relative hepatic impairment seen in the elderly [3,11,29].…”

“…Epidemiological studies indicate that adverse drug reactions (ADRs) produced by drug interactions affect progressively from hospitalized patients to outpatients, where there is usually lack of monitoring and professional care. Hypothetically, the estimation of probabilities of potential interactions through combinatorial analysis reveals, for example, that co-administration of 3, 5 or 7 drugs provides interaction chances of 15, 50 or 100%, respectively [3]. Furthermore, over 80% of registered ADRs are characterized as type A, i.e., arising from an exaggerated, dose-dependent drug effect and, by definition, are predictable and preventable, in contrast to the low prevalence of type B ADRs, i.e., unexpected reactions and disconnected from the action of the drug (idiosyncratic) [4].…”