Division of Pulmonary and Sleep Medicine, Bethesda North Hospital, Cincinnati, OH, USA.
Adjunct Professor of Medicine, Division of Cardiology, The Ohio State University, Columbus, Ohio, USA.
Sleep. 2024 Aug 14;47(8). doi: 10.1093/sleep/zsae038.
Medication-induced central sleep apnea (CSA) is one of the eight categories of causes of CSA but in the absence of awareness and careful history may be misclassified as primary CSA. While opioids are a well-known cause of respiratory depression and CSA, non-opioid medications including sodium oxybate, baclofen, valproic acid, gabapentin, and ticagrelor are less well-recognized. Opioids-induced respiratory depression and CSA are mediated primarily by µ-opioid receptors, which are abundant in the pontomedullary centers involved in breathing. The non-opioid medications, sodium oxybate, baclofen, valproic acid, and gabapentin, act upon brainstem gamma-aminobutyric acid (GABA) receptors, which co-colonize with µ-opioid receptors and mediate CSA. The pattern of ataxic breathing associated with these medications is like that induced by opioids on polysomnogram. Finally, ticagrelor also causes periodic breathing and CSA by increasing central chemosensitivity and ventilatory response to carbon dioxide. Given the potential consequences of CSA and the association between some of these medications with mortality, it is critical to recognize these adverse drug reactions, particularly because discontinuation of the offending agents has been shown to eliminate CSA.
药物引起的中枢性睡眠呼吸暂停（CSA）是 CSA 八种病因之一，但由于缺乏认识和仔细的病史，可能被误诊为原发性 CSA。虽然阿片类药物是呼吸抑制和 CSA 的已知原因，但包括羟丁酸钠、巴氯芬、丙戊酸、加巴喷丁和替格瑞洛在内的非阿片类药物则不太为人所知。阿片类药物引起的呼吸抑制和 CSA 主要是通过 µ 阿片受体介导的，µ 阿片受体在参与呼吸的桥脑延髓中枢中大量存在。非阿片类药物羟丁酸钠、巴氯芬、丙戊酸和加巴喷丁作用于脑脑干γ-氨基丁酸（GABA）受体，GABA 受体与 µ 阿片受体共同定植，并介导 CSA。这些药物引起的共济失调性呼吸与阿片类药物在多导睡眠图上诱导的呼吸模式相似。最后，替格瑞洛通过增加中枢化学敏感性和对二氧化碳的通气反应也会引起周期性呼吸和 CSA。鉴于 CSA 的潜在后果以及其中一些药物与死亡率之间的关联，识别这些药物不良反应至关重要，特别是因为已经证明停用引起 CSA 的药物可消除 CSA。
