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

老年人的药物相互作用以及与阿片类药物相关的急诊室就诊和住院治疗

• 批准号: 10263197
• 负责人: Katsiaryna Bykov
• 金额: $ 40万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-30 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10263197
• 关键词: Drug; interactions; opioid; related; emergency

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.

老年人即使将这些药物作为阿片类药物相关的不良反应有高风险 规定。大约三分之一的老年人每年至少收到一个阿片类药物处方 接受高量，平均剂量超过了药物标签的建议。阿片类药物是 负责超过35,000次急诊室就诊，近125,000次住院和近9,000 每年老年人死亡。使用阿片类药物的老年人中的一多药特别高。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拥有许多其他 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填充52 每年大约10种药物的处方。较旧的许多药物通常使用 成年人可能与阿片类药物相互作用，以增加阿片类药物相关的不良事件的风险。例如，羟考酮，一个 最常用的用于慢性疼痛的药物和阿片类药物最常涉及的药物 过量服用，由肝酶细胞色素P450 3A4（CYP3A4）和CYP2D6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，抑制CYP3A4。这些药物之间的相互作用可能会增加羟考酮 体内的浓度并可能增加导致阿片类药物相关的不良事件的风险 室访和住院。芬太尼还通过3A4代谢，氢可酮由2d6代谢，然后 Tramadol由3A4、2D6和2B6代谢。尽管药物相互作用可能具有重要作用 在老年人中玩耍，对这些推定的相互作用是否可能增加阿片类药物有关 急诊室就诊和住院以及患者是否有更安全的治疗方法 需要阿片类药物治疗。该项目的总体目标是产生新的证据，以帮助 患者和医疗保健提供者确定并避免与具有的阿片类药物进行重要的药物相互作用 增加与阿片类药物相关的急诊室就诊和住院风险的潜力。这个项目将重点放在 通常影响较老的三种合并症（抑郁，高血压和急性冠状动脉综合征） 成年人和某些药物可能与阿片类药物相互作用，但可以使用可能更安全的替代品。 该项目的具体目的是评估：（1）抑制2d6的SSRI（氟西汀，帕罗西汀） 使用阿片类药物相关的急诊室就诊和住院的发生率 羟考酮，氢可酮或曲马多； （2）抑制3A4的钙通道阻滞剂（CCB）（diltiazem， 维拉帕米（Verapamil 使用羟考酮，芬太尼或曲马多； （3）抑制2B6的抗血小板剂（氯吡格雷，ticlopidine） 使用阿片类药物相关的急诊室就诊和住院的发生率 曲马多。