Thigpen James C, Odle Brian L, Harirforoosh Sam
Department of Pharmacy Practice, Gatton College of Pharmacy, East Tennessee State University, Johnson City, TN, USA.
Department of Pharmaceutical Sciences, Gatton College of Pharmacy, East Tennessee State University, Box 70594, Johnson City, TN, 37614-1708, USA.
Eur J Drug Metab Pharmacokinet. 2019 Oct;44(5):591-609. doi: 10.1007/s13318-019-00552-0.
Pain management in the pediatric population is complex for many reasons. Mild pain is usually managed quite well with oral acetaminophen or ibuprofen. Situations involving more severe pain often require the use of an opioid, which may be administered by many different routes, depending on clinical necessity. Acute and chronic disease states, as well as the constantly changing maturational process, produce unique challenges at every level of pediatrics in dosing and management of all medications, especially with regard to high-risk opioids. Although there has been significant progress in the understanding of opioid pharmacokinetics and pharmacodynamics in neonates, infants, children, and adolescents, somewhat limited data exist from which necessary information, concerning the safe and effective use of these agents, may be drawn. The evidence here provided is intended to be helpful in directing the practitioner to patient-specific reasons for preferring one opioid over another. As our knowledge of opioids and their effects has grown, it has become clear that older medications like codeine and meperidine (pethidine) have very limited use in pediatrics. This review provides pharmacokinetic and pharmacodynamic evidence on the currently available opioids: morphine, fentanyl (and derivatives), codeine, meperidine, oxycodone, hydrocodone, hydromorphone, methadone, buprenorphine, butorphanol, nalbuphine, pentazocin, ketobemidone, tramadol, piritramide, naloxone and naltrexone. Morphine, being the most studied opioid analgesic, is the standard against which all others are compared. Pharmacokinetic parameters of morphine that have been found in neonates, i.e., higher volume of distribution, immature metabolic processes that develop at various rates, elimination that is variable based on age and weight, as well as treated and untreated disease processes, are an example of all opioids in the population discussed in this review. Outside the premature and neonatal population, the use of opioids in infants, children, and adolescents quickly begins to resemble the established values found in adults. As such, the concerns (risks) of these medications become comparable to those seen in adults.
由于多种原因,儿科人群的疼痛管理很复杂。轻度疼痛通常使用口服对乙酰氨基酚或布洛芬就能很好地控制。涉及更严重疼痛的情况通常需要使用阿片类药物,根据临床需要,阿片类药物可以通过多种不同途径给药。急性和慢性疾病状态,以及不断变化的成熟过程,在儿科的各个层面上,在所有药物的给药和管理方面都带来了独特的挑战,尤其是对于高风险阿片类药物。尽管在理解新生儿、婴儿、儿童和青少年的阿片类药物药代动力学和药效动力学方面取得了重大进展,但有关这些药物安全有效使用的必要信息的数据仍然有限。此处提供的证据旨在帮助从业者了解针对特定患者选择一种阿片类药物而非另一种的原因。随着我们对阿片类药物及其作用的了解不断增加,很明显,像可待因和哌替啶(度冷丁)这样的老药在儿科的用途非常有限。本综述提供了关于目前可用阿片类药物的药代动力学和药效动力学证据:吗啡、芬太尼(及其衍生物)、可待因、哌替啶、羟考酮、氢可酮、氢吗啡酮、美沙酮、丁丙诺啡、布托啡诺、纳布啡、喷他佐辛、凯托米酮、曲马多、匹利卡明、纳洛酮和纳曲酮。吗啡是研究最多的阿片类镇痛药,是与所有其他药物进行比较的标准。在新生儿中发现的吗啡药代动力学参数,即分布容积较大、以不同速率发育的不成熟代谢过程、基于年龄和体重以及治疗和未治疗疾病过程而变化的消除情况,是本综述中所讨论人群中所有阿片类药物的一个例子。在早产儿和新生儿群体之外,婴儿、儿童和青少年中阿片类药物的使用很快就开始类似于在成人中发现的既定值。因此,这些药物的关注点(风险)与成人中所见的相当。