Medications that inhibit ductal closure

Medications that inhibit ductal closure

Inadvertent Relaxation of the Ductus Arteriosus by Pharmacologic Agents
that are Commonly Used in the Neonatal PeriodReese J, Veldman A, Shah L, Vucovich M, 
and Cotton, RB.  Semin Perinatol 2010; 34:224-230  

Premature birth and disruption of the normal maturation process leave the immature ductus
arteriosus unable to respond to postnatal cues for closure. Strategies that advocate
conservative management of the patent ductus arteriosus (PDA) in premature infants are
dependent on identification of the symptomatic PDA and understanding the risk factors that
predispose to PDA. Exposure of premature infants to unintended vasodilatory stimuli may
be one of the risk factors for PDA that is underrecognized. In this article, we summarize the
clinical factors that are associated with PDA and review commonly used neonatal drugs for
their vasodilatory properties. Data demonstrating relaxation of the ductus arteriosus by
gentamicin and other aminoglycoside antibiotics, by cimetidine and other H2 receptor
antagonists, and by heparin are provided as examples of neonatal therapies that have
unanticipated effects that may promote PDA.

Comments:

Date:            27 May 2010
Time:            09:40 AM

The authors of this thought-provoking article remind us that a balance in vasodilatory 
and contractile forces is required in order to obtain closure of the ductus arteriosus, 
describing how medications commonly prescribed during the antenatal and neonatal periods 
contribute to patency of the DA. Prostaglandins and COX inhibitors are efficient DA 
dilators, and nitric oxide produces vasodilation of most vascular beds including the DA. 
In addition, medications used during pregnancy, such as magnesium and other tocolytics, 
ACE inhibitors, antihistamines, and anticonvulsants, are associated with higher rates of 
PDA.

However, other medications of vasodilatory potential are also used commonly during the 
neonatal period, and, due to their early and extended administration, these drugs merit 
careful monitoring. Aminoglycosides – including gentamicin, and H2 antagonists and 
heparin are identified as potential mediators of ductus relaxation, perhaps contributing 
to persisting patency.

Additional studies are needed to determine whether these drugs represent significant 
clinical risk factors for PDA. In the meantime, we should consider the possibility that 
commonly used medications may deliver cumulative vasodilatory effects to the DA. Perhaps 
our interventions are producing unintended consequences.

UserName:        Alta Kendall BSN RNC-NIC
UserEmail:       alta@telebyte.com
UserTel:         360-434-0945
UserHOSP:        Tacoma General Hospital, Tacoma, WA

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