Drug interactions and opioid-related emergency room visits and hospitalizations among older adults

老年人即使在服用阿片类药物时，也会出现与阿片类药物相关的不良反应 开了处方。大约三分之一的老年人每年至少收到一张阿片类药物处方，许多 接受高剂量，平均剂量超过药品标签上的建议剂量。阿片类药物 负责35000多次急诊室就诊，近12.5万次住院治疗，近9000次 每年都有老年人死亡。使用阿片类药物的老年人中多药使用率特别高。AS 与不使用阿片类药物的患者相比，使用阿片类药物的患者更有可能患有其他许多疾病 合并症，包括抑郁症和心血管疾病。平均而言，使用阿片类药物的患者占52 每年约有10个药物类别开出处方。一些老年人常用的药物 成人可能与阿片类药物相互作用，增加与阿片类药物相关的不良事件的风险。例如，羟考酮，一 治疗慢性疼痛最常用的药物和阿片类药物中最常见的一种 过量，由肝酶细胞色素P450 3A4(细胞色素P450 3A4)和细胞色素P2D6代谢。精选的- 5-羟色胺再摄取抑制剂(SSRI)氟西汀和帕罗西汀是使用最广泛的 抗抑郁药物，抑制细胞色素P3A4。这些药物之间的相互作用可能会增加羟考酮 阿片类药物在体内的浓度并可能增加不良事件导致阿片类药物相关紧急情况的风险 探视房间和住院治疗。芬太尼也由3A4代谢，氢可酮由2D6代谢，以及 曲马多由3A4、2D6和2B6代谢。尽管药物相互作用可能会发挥重要的作用 在老年人中玩耍，几乎不知道这些假定的相互作用是否可能增加阿片类药物相关 急诊室就诊和住院，以及是否有更安全的治疗方案供患者选择 需要阿片类药物治疗。这个项目的首要目标是产生新的证据来帮助 患者和医疗保健提供者识别并避免与阿片类药物的重要相互作用 有可能增加与阿片类药物相关的急诊室就诊和住院风险。该项目将重点放在 通常影响老年人的三种并存疾病(抑郁症、高血压和急性冠脉综合征) 成人，某些药物可能与阿片类药物相互作用，但有可能更安全的替代品。 该项目的具体目的是评估：(1)抑制2D6(氟西汀、帕罗西汀)的SSRIs 使用阿片类药物的老年人与阿片类药物相关的急诊室就诊和住院率增加 羟考酮、氢可酮或曲马多；(2)抑制3A4(地尔硫卓， 维拉帕米)增加与阿片类药物相关的急诊室就诊和住院率 使用羟考酮、芬太尼或曲马多；以及(3)抑制2B6的抗血小板药物(氯吡格雷、噻氯匹定) 使用阿片类药物的老年人与阿片类药物相关的急诊室就诊和住院率增加 曲马多。

Older adults are at high risk of opioid-related adverse effects even when they use these medications as prescribed. Approximately one in three older adults receives at least one opioid prescription each year and many receive high amounts, with average doses that exceed recommendations on the drug labels. Opioids are responsible for more than 35,000 emergency room visits, nearly 125,000 hospitalizations, and nearly 9,000 deaths among older adults each year. Polypharmacy among older adults who use opioids is especially high. As compared to patients who do not use opioids, those that use opioids are more likely to have many other comorbidities, including depression and cardiovascular disease. On average, patients who use opioids fill 52 prescriptions per year from about 10 drug classes. A number of medications that are commonly used by older adults may interact with opioids to increase risk of opioid-related adverse events. For example, oxycodone, one of the most commonly used medications for chronic pain and the drug most frequently involved in opioid overdoses, is metabolized by the liver enzymes cytochrome P450 3A4 (CYP3A4) and CYP2D6. The selective- serotonin reuptake inhibitors (SSRIs) fluoxetine and paroxetine, which are among the most widely used antidepressant medications, inhibit CYP3A4. Interactions between these drugs could increase oxycodone concentrations in the body and potentially increase risk of adverse events leading to opioid-related emergency room visits and hospitalizations. Fentanyl is also metabolized by 3A4, hydrocodone is metabolized by 2D6, and tramadol is metabolized by 3A4, 2D6, and 2B6. Despite the potentially important role that drug interactions may play in older adults, little is known about whether these putative interactions are likely increase opioid-related emergency room visits and hospitalizations and whether there may be safer treatment alternatives for patients requiring opioid treatment. The overarching goal of this project is to generate novel evidence that will help patients and healthcare providers identify and avoid important drug interactions with opioids that have the potential to increase risk of opioid-related emergency room visits and hospitalizations. This project will focus on three comorbid conditions (depression, hypertension, and acute coronary syndromes) that commonly affect older adults and for which certain drugs may interact with opioids but where potentially safer alternatives are available. The specific aims of this project are to evaluate whether: (1) SSRIs that inhibit 2D6 (fluoxetine, paroxetine) increase rates of opioid-related emergency room visits and hospitalizations among older adults who use oxycodone, hydrocodone, or tramadol; (2) calcium channel blockers (CCBs) that inhibit 3A4 (diltiazem, verapamil) increase rates of opioid-related emergency room visits and hospitalizations among older adults who use oxycodone, fentanyl, or tramadol; and (3) antiplatelet agents that inhibit 2B6 (clopidogrel, ticlopidine) increase rates of opioid-related emergency room visits and hospitalizations among older adults who use tramadol.