Maternal use of cyclobenzaprine (Flexeril) may induce ductal closure and persistent pulmonary hypertension in neonates

Moreira, Alvaro; Barbin, Clay M.; Martinez, Hugo R.; Aly, Ashraf M.; Fonseca, Rafael

doi:10.3109/14767058.2013.850663

Cited by 9 publications

(4 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, we evaluated the possibility that SSRIs may indirectly cause PPHN by constricting the fetal DA. This notion is supported by a recent case report in which a full-term infant, exposed antenatally to a compound with SSRI properties, presented with elevated pulmonary artery pressure, right ventricular hypertrophy, and a completely closed DA, as revealed by an echocardiogram at 1 h of life (34). Interestingly, a study conducted by Lim et al (29) used Doppler ultrasound to measure right pulmonary artery flow characteristics (vessel diameter, vessel cross-sectional area, resistance, peak systolic velocity, flow rate, flow velocity) in 36-wk-old human fetuses, with or without long-term SSRI exposure.…”

Section: Discussionmentioning

confidence: 65%

Selective serotonin reuptake inhibitor exposure constricts the mouse ductus arteriosus in utero

Hooper

Delaney

Streeter

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Use of selective serotonin reuptake inhibitors (SSRIs) is common during pregnancy. Fetal exposure to SSRIs is associated with persistent pulmonary hypertension of the newborn (PPHN); however, a direct link between the two has yet to be established. Conversely, it is well known that PPHN can be caused by premature constriction of the ductus arteriosus (DA), a fetal vessel connecting the pulmonary and systemic circulations. We hypothesized that SSRIs could induce in utero DA constriction. Using isolated vessels and whole-animal models, we sought to determine the effects of two commonly prescribed SSRIs, fluoxetine and sertraline, on the fetal mouse DA. Cannulated vessel myography studies demonstrated that SSRIs caused concentration-dependent DA constriction and made vessels less sensitive to prostaglandin-induced dilation. Moreover, in vivo studies showed that SSRI-exposed mice had inappropriate DA constriction in utero. Taken together, these findings establish that SSRIs promote fetal DA constriction and provide a potential mechanism by which SSRIs could contribute to PPHN. mouse; ductus arteriosus; SSRI; fluoxetine; sertraline; serotonin; PPHN NEW & NOTEWORTHY This study is the first to elucidate a mechanism by which serotonin reuptake inhibitors (SSRIs) alter ductus arteriosus tone. It also puts forth the notion that SSRIs may contribute to persistent pulmonary hypertension of the newborn by causing premature fetal ductus constriction.THE DUCTUS ARTERIOSUS (DA) is an essential fetal vessel connecting the pulmonary and systemic circulations. During fetal life, the DA, responding to low oxygen tension, nitric oxide, and prostaglandin signaling, remains patent to shunt blood to the aorta, bypassing the immature, uninflated lungs. At birth, increasing blood oxygen content and decreasing prostaglandin levels stimulate DA closure, allowing appropriate perfusion of the newly inflated lungs (7,8,43,52). The timing of DA closure is tightly regulated. If the DA fails to close (patent DA), serious consequences including pulmonary hemorrhage, parenchymal lung disease, intraventricular hemorrhage, and death can ensue. Conversely, premature DA constriction in utero is also undesirable and can lead to life-threatening conditions, including right ventricular hypertrophy, functional pulmonary atresia, absent pulmonary valve syndrome, hydrops fetalis, and persistent pulmonary hypertension of the newborn (PPHN) (18,20,23,31,32).PPHN is a disorder characterized by sustained elevated pulmonary vascular resistance (PVR). During fetal life, PVR is high due to a number of factors, including mechanical compression of the pulmonary arterioles by fluid-filled alveoli, low fetal oxygen tension, low levels of vasodilators (prostacyclin, nitric oxide), and elevated levels of vasoconstrictors (endothelin-1, thromboxane) (37). At birth, PVR should fall to facilitate a smooth transition from fetal to extrauterine life. However, in some cases, the pulmonary vasculature fails to relax, causing PPHN, a disorder accompanied by hypoxemia and right-...

show abstract

Section: Discussionmentioning

confidence: 65%

Selective serotonin reuptake inhibitor exposure constricts the mouse ductus arteriosus in utero

Hooper

Delaney

Streeter

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

“…Cyclobenzaprine is considered safe during pregnancy and is one of the most commonly used analgesics for the treatment of PRLSP. Despite a report of early closure of the arterial duct, it is widely used in pregnant women 55 . It has a B classification from the FDA.…”

Section: Pharmacological Treatmentmentioning

confidence: 99%

Pregnancy-related lumbosacral pain

Aragão¹

2019

Brazilian Journal of Pain

View full text Add to dashboard Cite

BACKGROUND AND OBJECTIVES: Pregnancy causes physiological and anatomical changes in the woman's body, affecting several systems such as the musculoskeletal. During pregnancy or in the postpartum period, these changes may cause low back pain or low pelvic pain, preventing the normal movement of these structures and causing suffering. The objective of this study was to discuss the diagnosis and treatment of pregnancy-related lumbosacral pain, focusing on terminology, epidemiology, risk factors, pathophysiology, prognosis, diagnosis, and treatment. CONTENTS: We searched the literature in Pubmed, Cochrane Library, Ovid and Google using the terms "low back pain", "pelvic girdle pain", "lumbopelvic pain", "posterior pelvic pain", "pregnancy-related low back pain", "pregnancy-related pelvic girdle pain" and "pregnancy-related lumbopelvic pain", for articles in English, Portuguese and Spanish in the last 20 years or older, where relevant. CONCLUSION: Pregnancy is one of the main causes of lumbosacral pain, and one of the most frequent diseases during gestation. The correct management of this pathology reduces negative impacts on the life of pregnant women.

show abstract

“…It is considered safe during pregnancy and is one of the most commonly used analgesics for the treatment of pregnancy-related low back pain. Despite a report of early closure of the ductus arteriosus, this drug is already widely used in pregnant women 54 . It is Class B by the FDA.…”

Section: Cyclobenzaprinementioning

confidence: 99%

Pharmacological treatment of pain in pregnancy

Aragão¹,

Tobias²

2019

Brazilian Journal of Pain

View full text Add to dashboard Cite

BACKGROUND AND OBJECTIVES: Non-obstetric causes of pain during pregnancy are very common and can be disabling if not treated properly. The objective of this study is to discuss the pharmacological treatment of pain during pregnancy with a focus on drug classification and pregnancy use, therapy options, teratogenicity, increased fetal malformations and gestational complications associated with the use of therapy. CONTENTS: During pregnancy, the body goes through several anatomical and physiological changes. These changes can precipitate pain, which in some cases can lead to disability. In addition, pregnancy may exacerbate pre-existing painful conditions. The choice to prescribe a drug to a pregnant woman is difficult. The changes in the body of a pregnant woman influence drug absorption, distribution, metabolism, and excretion, and may alter the expected response. CONCLUSION: The risks and benefits of the drug for the mother and the child should be considered, weighing the risks of not treating the disease adequately during pregnancy.

show abstract

Maternal use of cyclobenzaprine (Flexeril) may induce ductal closure and persistent pulmonary hypertension in neonates

Cited by 9 publications

References 18 publications

Selective serotonin reuptake inhibitor exposure constricts the mouse ductus arteriosus in utero

Selective serotonin reuptake inhibitor exposure constricts the mouse ductus arteriosus in utero

Pregnancy-related lumbosacral pain

Pharmacological treatment of pain in pregnancy

Contact Info

Product

Resources

About