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

老年人即使在使用这些药物时，也有很高的风险发生阿片类药物相关的不良反应。 规定的。大约三分之一的老年人每年至少接受一次阿片类药物处方， 接受高剂量，平均剂量超过药物标签上的建议。阿片类药物是 负责超过35，000次急诊，近125，000次住院，近9，000次 每年都有老年人死亡。使用阿片类药物的老年人中的多药使用率特别高。作为 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许多其他疾病。 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种药物。老年人常用的一些药物 成人可能与阿片类药物相互作用，增加阿片类药物相关不良事件的风险。例如，羟考酮， 最常用的慢性疼痛药物和最常涉及阿片类药物的药物 过量，通过肝酶细胞色素P450 3A 4（CYP 3A 4）和CYP 2D 6代谢。选择性- 5-羟色胺再摄取抑制剂（SSRIs）氟西汀和帕罗西汀，这是最广泛使用的 抗抑郁药物，抑制CYP 3A 4。这些药物之间的相互作用可能会增加羟考酮 在体内的浓度，并可能增加不良事件的风险，导致阿片类药物相关的紧急情况 房间访问和住院治疗。芬太尼也通过3A 4代谢，氢可酮通过2D 6代谢， 曲马多通过3A 4、2D 6和2B 6代谢。尽管药物相互作用可能具有潜在的重要作用， 在老年人中，人们对这些假定的相互作用是否可能增加阿片类药物相关性知之甚少 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， 患者和医疗保健提供者识别并避免与阿片类药物的重要药物相互作用， 可能增加阿片类药物相关急诊和住院的风险。该项目将重点关注 三种共病（抑郁症、高血压和急性冠脉综合征）通常影响老年人 对成年人而言，某些药物可能与类阿片发生相互作用，但有可能更安全的替代品。 本项目的具体目的是评价：（1）抑制2D 6的SSRIs（氟西汀、帕罗西汀） 使用阿片类药物的老年人中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3A 4的钙通道阻滞剂（CCB）（地尔硫卓， 维拉帕米）增加了老年人中与阿片类药物相关的急诊室就诊率和住院率， 使用羟考酮、芬太尼或曲马多;（3）抑制2B 6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中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.