Potential drug-drug interactions in Alzheimer patients with behavioral symptoms

Abstract

The use of multi drug regimens among the elderly population has increased tremendously over the last decade although the benefits of medications are always accompanied by potential harm, even when prescribed at recommended doses. The elderly populations are particularly at an increased risk of adverse drug reactions considering comorbidity, poly-therapy, physiological changes affecting the pharmacokinetics and pharmacodynamics of many drugs and, in some cases, poor compliance due to cognitive impairment and/or depression. In this setting, drug-drug interaction may represent a serious and even life-threatening clinical condition. Moreover, the inability to distinguish drug-induced symptoms from a definitive medical diagnosis often results in addition of yet another drug to treat the symptoms, which in turn increases drug-drug interactions. Cognitive enhancers, including acetylcholinesterase inhibitors and memantine, are the most widely prescribed agents for Alzheimer's disease (AD) patients. Behavioral and psychological symptoms of dementia, including psychotic symptoms and behavioral disorders, represent noncognitive disturbances frequently observed in AD patients. Antipsychotic drugs are at high risk of adverse events, even at modest doses, and may interfere with the progression of cognitive impairment and interact with several drugs including anti-arrhythmics and acetylcholinesterase inhibitors. Other medications often used in AD patients are represented by anxiolytic, like benzodiazepine, or antidepressant agents. These agents also might interfere with other concomitant drugs through both pharmacokinetic and pharmacodynamic mechanisms. In this review we focus on the most frequent drug-drug interactions, potentially harmful, in AD patients with behavioral symptoms considering both physiological and pathological changes in AD patients, and potential pharmacodynamic/pharmacokinetic drug interaction mechanisms.

Keywords: AChEIs; Alzheimer; antipsychotic; drug–drug interaction.

Figure 1

Pharmacodynamic drug–drug interaction in a cholinergic synapse: acetylcholinesterase inhibitor (AChEI) and anti-muscarinic drug. Notes: The concomitant administration of AChEIs (green triangles) and anticholinergic drugs may result in a pharmacodynamic interaction in the synapse where the beneficial increment of acetylcholine (blue circle), related to AChE (blue triangles) inhibition, is at least partially reversed by anti-muscarinic drugs (red ellipse) at receptor levels (blue bars).