When Pollutants Meet Pharmaceuticals: Pollutant-Drug Interactions and Their Hidden Impact on Human Health

Environmental pollutants and pharmaceutical wastes increasingly coexist in environmental and biological systems, but their combined health effects remain poorly understood. This narrative review examines interactions between commonly used drugs, including antibiotics, vaccines, nonsteroidal anti-inflammatory drugs (NSAIDs), psychotropic drugs, paracetamol, and phosphodiesterase type 5 (PDE5) inhibitors, and major environmental pollutants such as microplastics, perfluoroalkyl and polyfluoroalkyl substances (PFAS), heavy metals, disinfectant biocides, arsenic, and nitrates. Evidence suggests that these interactions can alter drug bioavailability, therapeutic efficacy, toxicity, and resistance dynamics through adsorption, oxidative stress, immune modulation, and coselection mechanisms. Microplastics can adsorb antibiotics, favoring the emergence and spread of antimicrobial resistance, while also transporting psychotropic drugs and increasing their bioavailability after ingestion. PFAS exposure has been associated with a lower antibody response to tetanus vaccines in children and enhanced horizontal transfer of antibiotic resistance genes. Heavy metals and disinfectant biocides can further coselect for antibiotic resistance through shared mobile genetic elements and cross-resistance mechanisms. Current evidence is dominated by experimental and environmental studies, whereas clinically relevant human data remain limited. A central objective of this manuscript is to encourage research that addresses current knowledge gaps in this field, particularly through environmentally realistic mixing models, longitudinal exposure studies, and mechanistic multiomics approaches to improve toxicological risk assessment and public health strategies.