Table 2.

Proposed Mechanisms to Elucidate the Impact of Polypharmacy on Functional Status

Factors	Proposed Mechanism
Age-related regression of function reserve affects drug pharmacokinetics and pharmacodynamics	Reduced physiologic resilience and altered drug metabolism and/or drug clearance increases susceptibility to adverse drug reactions. Medication dose-adjustments may be warranted, if applicable.
Increased number of medical conditions increases the risk for drug-disease interactions and/or drug-geriatric syndrome interactions	A drug-disease interaction is an event in which a drug intended for therapeutic use causes harmful effects due to a comorbid disease, condition or syndrome (e.g., using diphenhydramine for seasonal allergies in a patient with cognitive impairment or a history of falls).
Increased number of medications increases the risk for drug-related toxicities or drug-drug interactions	Increased number of medications may lead to cumulative drug toxicity. The risk for drug-drug interactions approach 100% when 8 or more medications are used concurrently.
Use of medications in which the risk outweighs the benefit	Benzodiazepines and anticholinergic drugs (e.g., oxybutynin, amitriptyline) may interfere with memory, alertness, and orientation, leading to delirium, falls/fractures, and other adverse reactions.