Neonatal complications after the administration of indomethacin for preterm labor

Norton, Melanie; Merrill, Jeffrey D.; Cooper, Bernard A.; Kuller, Jeffrey A.; Clyman, Ronald I.

doi:10.1016/0020-7292(94)90439-1

Cited by 56 publications

(77 citation statements)

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“…Translated to the clinical situation, this new concept on indomethacin action well accounts for several observations in the management of the prematurely born infant. Not only does it provide a reason for the higher incidence of a persistent duct in infants from pregnancies complicated by NSAID intake ( Norton et al , 1993 ; Suarez et al , 2002 ), but also allows to interpret the way premature infants often respond to NSAID treatment ( Ohlsson et al , 2004 ; Shah and Ohlsson, 2004 ). Quite commonly, in fact, patients present a transient constriction of their duct that may not become permanent upon repeated courses of drug.…”

Section: Discussionmentioning

confidence: 99%

“…Available data accord with this possibility. Antenatal exposure to COX inhibitors, whether dual (COX1/COX2) or isoform specific, increases the incidence of patent ductus in the neonate ( Norton et al , 1993 ; Loftin et al , 2002 ; Suarez et al , 2002 ), and this outwardly paradoxical finding could reflect the increased importance of a compensatory mechanism. The same explanation may also account for the frequent failure of COX inhibitors, such as indomethacin and ibuprofen, to close a patent ductus in the premature infant despite their adequate concentration in the circulation and a transient constriction to the compounds attesting to their intrinsic efficacy ( Ohlsson et al , 2004 ; Shah and Ohlsson, 2004 ).…”

Section: Introductionmentioning

confidence: 99%

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Indomethacin promotes nitric oxide function in the ductus arteriosus in the mouse

Sodini

Baragatti

Barogi

et al. 2008

British J Pharmacology

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Background and purpose: Prenatal patency of ductus arteriosus is maintained by prostaglandin (PG) E 2 in concert with nitric oxide (NO) and carbon monoxide (CO). Accordingly, we have previously found that NO activity increases upon deletion of either COX. Here, we have examined whether COX inhibition by indomethacin mimics COX deletion in promoting NO. Experimental approach: Experiments were performed in vitro and in vivo with wild-type (WT) and eNOSÀ/À, near-term mouse foetuses. Indomethacin was given p.o. to the mother as single (acute treatment) or repeated (daily for 3 days; chronic treatment) doses within a therapeutic range (2 mg kg À1 ). Key results: Indomethacin promoted eNOS mRNA expression in the WT ductus. Coincidentally, the drug enhanced the contraction of the isolated ductus to the NOS inhibitor, N G -nitro-L-arginine methyl ester, and its effect augmented with the length of treatment. No such enhancement was seen with the eNOSÀ/À ductus. Chronic indomethacin also increased, albeit marginally, the contraction of the WT ductus to the CO synthesis inhibitor, zinc protoporphyrin. Whether given acutely or chronically, indomethacin induced a little narrowing of the ductus antenatally and had no effect on postnatal closure of the vessel. Conclusions and implications:We conclude that activation of NO and, to a much lesser degree, CO mechanisms is an integral part of the indomethacin effect on the ductus. This relaxing influence may oppose the contraction from PGE 2 suppression and could explain the failures of indomethacin therapy in premature infants with persistent duct.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Indomethacin promotes nitric oxide function in the ductus arteriosus in the mouse

Sodini

Baragatti

Barogi

et al. 2008

British J Pharmacology

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“…Indomethacin is known to give rise to in utero closure of ductus arteriosus (32), and in some animals cyclooxygenase 2 (COX2) inhibitors seem to have similar effects (33). Prenatal closure of ductus arteriosus may result in right ventricular overload and even in cardiac arrest in the fetus; in the neonate, it may give rise to pulmonary hypertension.…”

Section: Reasons For Cautionmentioning

confidence: 99%

The potential benefits of using fish oil in relation to preterm labor: the case for a randomized controlled trial?

Olsen

Bjornsson

et al. 2003

Acta Obstet Gynecol Scand

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“…COX‐2 is the predominant isoform in foeto‐placental membranes and myometrium ( Slater et al ., 1995 ; 1997 ), whereas the constitutive isoform, COX‐1, is expressed in foetal tissues. Nimesulide is therefore a potentially useful tocolytic agent ( Sawdy, 1997 ), enabling the targeting of foeto‐placental and uterine COX and avoiding the harmful foetal side effects that preclude the use of non‐selective COX‐inhibitors such as indomethacin ( Norton et al ., 1993 ).…”

Section: Introductionmentioning

confidence: 99%

Calcium antagonistic properties of the cyclooxygenase‐2 inhibitor nimesulide in human myometrial myocytes

Knock

Aaronson

1999

British J Pharmacology

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1 The non-steroidal anti-in¯ammatory drug nimesulide is a selective inhibitor of cyclooxygenase-2 which relaxes spontaneously contracting human myometrium in vivo and is potentially a useful tocolytic drug. Part of the relaxant action of nimesulide may be via block of myometrial Ca 2+ channels. Here, we describe the Ca 2+ channel blocking properties of nimesulide in freshly dispersed human term-pregnant myometrial smooth muscle cells (HMSMCs). 2 Both L-and T-components of the whole cell Ca 2+ channel current were inhibited by 100 mM nimesulide (38+3 and 35+1% block, respectively). At physiological pH inside and outside the cell (pH o /pH i =7.4/7.2), this block did not depend on the holding or test potential, although a degree of use-dependence was observed during high frequency stimulation at a higher concentration of drug (300 mM). 3 At pH o /pH i =6.8, under which condition the concentration of the non-ionized form of the drug is increased 3 fold compared to pH 7.4, nimesulide blocked the L-type current more potently (58+3% inhibition at 100 mM, P50.01) compared to physiological pH. Nimesulide caused a 7 mV leftward shift in the availability curve of the current at pH 6.8, suggesting that the anity of the drug for the inactivated channel is approximately 4 fold higher than its anity for the closed channel. We speculate that acidi®cation and depolarization of the myometrium during the intense and prolonged contractions of labour might increase the potency of nimesulide as a Ca 2+ channel antagonist, promoting its action as a tocolytic agent.

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Neonatal complications after the administration of indomethacin for preterm labor

Cited by 56 publications

References 0 publications

Indomethacin promotes nitric oxide function in the ductus arteriosus in the mouse

Indomethacin promotes nitric oxide function in the ductus arteriosus in the mouse

The potential benefits of using fish oil in relation to preterm labor: the case for a randomized controlled trial?

Calcium antagonistic properties of the cyclooxygenase‐2 inhibitor nimesulide in human myometrial myocytes

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