哺乳期禁用ACEI和ARB类（卡托普利、依那普利除外）

2012年版的妊娠高血压疾病诊治指南中说：哺乳期可继续应用产前使用的降压药物，禁用ACEI和ARB类（卡托普利、依那普利除外），请问为什么把卡托普利和依那普利除外？

查到两篇不算很老的文章关于卡托普利的，依那普利的文章没有找到

文章大意是妊娠期和哺乳期使用卡托普利会影响小鼠的行为。既然如此就提示这个药在妊娠和哺乳期使用都存在神经系统致畸的问题。
我觉得指南里的依据就显得乏力了，毕竟只是III B，从安全性的角度考虑，还是换药最妥当。既然有风险，应该视风险从大的原则。

Clin Exp Pharmacol Physiol. 2009 May;36(5-6):495-500. doi: 10.1111/j.1440-1681.2008.05108.x. Epub 2008 Oct 28.

Behavioural changes induced by angiotensin-converting enzyme inhibition during pregnancy and lactation in adult offspring rats.

Mecawi AS1, Araujo IG, Fonseca FV, Almeida-Pereira G, Côrtes WS, Rocha FF, Reis LC.

Abstract
1. The use of angiotensin-converting enzyme (ACE) inhibitors during pregnancy is contraindicated because of their association with increased risks of fetopathy, including central nervous systems malformations. In addition, some reports have shown that renin-angiotensin system components are expressed differently during embryonic development and adulthood in the rat. 2. Because angiotensin II and its derivative peptides have been implicated in anxiety and modulation of nociception, the aim of the present study was to investigate whether inhibiting ACE during prenatal and neonatal periods would alter behavioural plasticity in adult male offspring rats. 3. Female Wistar rats were treated with captopril (2 mg/mL water; approximately 200 mg/kg per day) during pregnancy and lactation. At adulthood, the offspring were subjected to the open field, elevated plus maze, social interaction, forced swimming and tail flick tests. 4. Perinatal captopril treatment significantly increased ambulation (33%; P < 0.05) and decreased resting time (37.5%; P < 0.05) in the open field test. Perinatal captopril treatment did not alter any of the behavioural parameters of the elevated plus maze; however, captopril treatment did cause a significant increase in social interaction (75.3%; P < 0.05). In the forced swimming test, there was an increased latency period (102.9%; P < 0.001) and a decreased immobility period (38.7, P < 0.05) in rats treated with perinatal captopril. In the tail flick test, perinatal captopril treatment significantly reduced the latency time (26.3%; P < 0.01). 5. The data show that ACE inhibition during prenatal and neonatal periods affects behavioural responses in adult offspring rats, suggesting that ACE is required for the development of neural systems that are associated with adult anxiety and nociceptive behavioural responses.

这篇提示是可能影响水盐平衡
Physiol Behav. 2010 Jan 12;99(1):118-24. doi: 10.1016/j.physbeh.2009.10.018.

Ontogenetic role of angiontensin-converting enzyme in rats: thirst and sodium appetite evaluation.

Mecawi AS1, Araujo IG, Rocha FF, Coimbra TM, Antunes-Rodrigues J, Reis LC.

Abstract
We investigated the influence of captopril (an angiotensin converting enzyme inhibitor) treatment during pregnancy and lactation period on hydromineral balance of the male adult offspring, particularly, concerning thirst and sodium appetite. We did not observe significant alterations in basal hydromineral (water intake, 0.3M NaCl intake, volume and sodium urinary concentration) or cardiovascular parameters in adult male rats perinatally treated with captopril compared to controls. However, male offspring rats that perinatally exposed to captopril showed a significant attenuation in water intake induced by osmotic stimulation, extracellular dehydration and beta-adrenergic stimulation. Moreover, captopril treatment during perinatal period decreased the salt appetite induced by sodium depletion. This treatment also attenuated thirst and sodium appetite aroused during inhibition of peripheral angiotensin II generation raised by low concentration of captopril in the adult offspring. Interestingly, perinatal exposure to captopril did not alter water or salt intake induced by i.c.v. administration of angiotensin I or angiotensin II. These results showed that chronic inhibition of angiotensin converting enzyme during pregnancy and lactation modifies the regulation of induced thirst and sodium appetite in adulthood.

嗯，我也觉得能不用尽量还是不要用这两种药，还是存在风险的，谢谢版主的详细解释！

谢分享！

这个两个药好象是不需要经过肝脏转化的，其他的药物都是前体药物

lxyzzj 发表于 2014-11-24  10:09
这个两个药好象是不需要经过肝脏转化的，其他的药物都是前体药物

确定？我看到的是卡托普利是需要经肝脏转化的非前体药物，贝那普利不经肝脏转化，依那普利好像是前体药物吧