Polypharmacy in Chronic Diseases: A Mechanistic and Clinical Review of Drug– Drug Interactions in Elderly Patients

Abstract

The use of multiple drugs, often five or more, is a major global health concern, particularly among elderly individuals with multimorbidity. The frequency of polypharmacy varies from 45–96% in hospitalized patients to 4–39% in older people living in the community and 38–91% in residents of nursing homes. It is caused by things like self-medication with over-the-counter medications, poor medication histories, specialist prescribing, and chronic disease management. This intricacy increases the likelihood of drug-drug interactions (DDIs), adverse drug reactions, and prescribing cascades, which occur when side symptoms are mistaken as new conditions, leading to additional medication and less adherence. Age-related pharmacokinetic changes, such as reduced renal and hepatic clearance (e.g., CYP450 inhibition/induction affecting absorption, metabolism, or excretion) or pharmacodynamic effects (additive, synergistic, or antagonistic actions), exacerbate DDIs caused by pharmacokinetic mechanisms. Polypharmacy increases DDIs in chronic conditions: type 2 diabetes causes hypoglycemia from sulfonylureas-NSAIDs; COPD causes bronchospasm from beta-agonists with non-selective beta-blockers; neurodegenerative cases risk serotonin syndrome or bradyarrhythmias from cholinesterase inhibitors with anticholinergics; and cardiovascular patients experience hypotension from amlodipine-furosemide or bleeding from heparinaspirin. Medication reconciliation, deprescribing unnecessary medications, multidisciplinary teams of doctors, pharmacists, and nurses, and tools like Micromedex or Lexicomp for identifying moderate-to-severe interactions are all key components of management methods. In an effort to balance therapeutic advantage against risks for better results and lower healthcare costs, routine clinical parameter monitoring, pharmacogenomics, and patient education further minimize harms.