Unexpected extra‐renal effects of loop diuretics in the preterm neonate

Abstract

The loop diuretics furosemide and bumetanide are commonly used in neonatal intensive care units (NICUs). Furosemide, due to its actions on the ubiquitous NKCC1 co-transporter and its promotion of prostanoid production and release, also has non-diuretic effects on vascular smooth muscle, airways, the ductus arteriosus, and theoretically the gastrointestinal tract. Loop diuretics also affect the central nervous system through the inhibitory neurotransmitter, GABA. Conclusion The loop diuretics have a variety of biological effects that are potentially harmful as well as beneficial. Care should be taken with the use of these agents since the range of their effects may be broader than the single action sought by the prescribing physician.

Diagnosis and Management of Patent Ductus Arteriosus

“…Certain diuretics, such as furosemide, can prevent a ductus from closing (42) and are not recommended in the first 1 to 3 weeks, when the greatest decrease in ductus diameter occurs spontaneously. Conservative measures also include avoidance of other drugs that promote ductus arteriosus relaxation (43) and proactive use of agents like caffeine that are associated with lower rates of PDA.…”

Furosemide suppresses ileal and colonic contractility via interactions with GABA‐A receptor in mice

“…NKCC1 and CFTR are widely expressed throughout the body including the gastrointestinal (GI) tract. Therefore, in addition to the role of furosemide in enhancing urine output, some studies have reported its non‐diuretic effects, including effects on vascular smooth muscle, airways, ductus arteriosus, the brain, and possibly the GI tract …”

“…Therefore, in addition to the role of furosemide in enhancing urine output, some studies have reported its non-diuretic effects, including effects on vascular smooth muscle, airways, ductus arteriosus, the brain, and possibly the GI tract. 5 Some previous studies have shown the side effects of taking furosemide on the GI tract including nausea, diarrhoea and constipation; 6 however, the direct effect of furosemide on the GI tract is still unclear. Constipation commonly occurs when stools move too slowly through the GI tract, and the intestine, especially the colon, absorbs too much water from the stool, causing it to become hard and dry.…”

Further studies of GABA and Glutamate imbalances in autism are important challenges for future research

“…NKCC1 transports Cl − , along with Na + and K + , into the neuron, which increases (Cl − ) leading to depolarisation (excitatory state) on the opening of Cl − channels, such as GABA‐A receptors. KCC2 transports Cl − , along with K + , out of the neuron, which decreases (Cl − ) leading to hyperpolarisation (inhibitory state) with Cl − channel opening . NKCC1 is widely distributed throughout the body and is also found in neurons .…”