Tag: ibuprofen

Choice of NSAID for closure of patent ductus arteriosus?

May 9, 2021 / / 0 Comments

Why is indometacin a drug of choice for closing the ductus arteriosus post-partum? As the ductus arteriosus is kept open by PGE2, may I know why other NSAIDs or paracetamol are not as ideal for this purpose?

The ductus arteriosus allows blood to bypass the lungs in utero but should close after birth. Cyclo-oxygenase-2 (COX-2) mediated production of prostaglandin E2 (PGE2) is important in keeping the ductus arteriosus open in utero. Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit COX-2 when administered at analgesic and anti-inflammatory doses. Therefore, the risk of premature closure of the ductus arteriosus is one reason for the contraindication of NSAIDs in the third trimester of pregnancy.

Patent ductus arteriosus (PDA) occurs when the ductus arteriosus fails to close after birth. NSAIDs can help to close the PDA. Older NSAIDs are typically used because there is a longer history of use and so better knowledge of the risks in infants. Either indometacin, also known as indomethacin (USAN), or ibuprofen is usually used. Paracetamol has also been used as it is has been considered safer in young children. It is not as effectively or widely used, but that it works at all shows that paracetamol can in certain situations inhibit COX-2 in vivo outside of the CNS. Newer NSAIDs are typically not preferred as clinical trials rarely include newborn infants, and so their safety in infants is poorly understood.

Paracetamol for osteoarthritis or rheumatoid arthritis?

May 9, 2021 / / 0 Comments

Some guidelines say paracetamol is only suitable for osteoarthritis, not rheumatoid arthritis (RA), as it is a poor anti-inflammatory. However, further reading online indicates that paracetamol is still used for other inflammatory rheumatological disorders like gout and RA. May I seek further clarification on this point?

Paracetamol (acetaminophen) is no longer recommended as a first-line for the pain associated with osteoarthritis (OA) as it has only small, non-clinically significant effects on the pain and there are safety concerns over long-term use for osteoarthritis (e.g., Macahdo et al., 2015; Roberts et al., 2016). Previously, paracetamol alone was used for the pain associated with OA if there was no significant inflammation following the damage to the joints. However, paracetamol is rarely sufficient for the pain associated with gout or RA. As there is always inflammation in gout and RA, a drug that is both analgesic and anti-inflammatory, such as a non-steroidal anti-inflammatory drug (NSAID), is usually preferable. So you will typically find paracetamol in evidence-based medicine guidelines for OA but not for RA or gout.

However, paracetamol will still cause analgesia. Therefore, you will still find it used sometimes as a safer option in cases when the pain is mild or as an addon between doses of ibuprofen (which happens to have a similar dosing interval) to provide additional analgesia. In addition, for patients for whom NSAIDs are contraindicated, you will often find paracetamol used.

References:
Machado GC, Maher CG, Ferreira PH, Pinheiro MB, Lin CW, Day RO, McLachlan AJ, Ferreira ML. Efficacy and safety of paracetamol for spinal pain and osteoarthritis: systematic review and meta-analysis of randomised placebo controlled trials. BMJ. 2015;350:h1225.
Roberts E, Delgado Nunes V, Buckner S, Latchem S, Constanti M, Miller P, Doherty M, Zhang W, Birrell F, Porcheret M, Dziedzic K, Bernstein I, Wise E, Conaghan PG. Paracetamol: not as safe as we thought? A systematic literature review of observational studies. Ann Rheum Dis. 2016;75(3):552.

Cyclooxygenase inhibitors for closure of the ductus arteriosus

September 25, 2018 / / 0 Comments

Why is it that older non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen or indomethacin, not newer NSAIDs, such as etoricoxib, are used to promote closure of patent ductus arteriosus in preterm infants?

In the fetus, the ductus arteriosus acts as a lung bypass diverting blood from the pulmonary artery into the aorta.  After birth, the ductus arteriosus constricts and is eventually obliterated. In preterm births, the ductus arteriosus may remain patent resulting in insufficient blood flow through the pulmonary circulation and increased risk of mortality.

Prostaglandin E2 (PGE2) is a vasodilator promoting patency of the ductus arteriosus. NSAIDs inhibit the cyclooxygenase (COX) enzyme responsible for producing  PGE2. NSAIDs are therefore contraindicated in the third trimester of pregnancy as they can cause premature closure of the ductus arteriosus in utero. However, in preterm infants, NSAIDs can be valuable in enabling closure of patent ductus arteriosus (PDA).

The NSAIDs used are typically ibuprofen or indomethacin. These are older NSAIDs for which there is a longer history of experience with use in infants. Ibuprofen is generally the preferred agent as it has a lower risk of reducing gastrointestinal and renal blood flow resulting in necrotizing enterocolitis and transient renal insufficiency. The newer coxibs, such as etorixocib, are not used because there is less knowledge of their safety in infants.

Reference:

Philips III, JB (2018) Management of patent ductus ateriosus in preterm infants. Garcia-Prats JA, Fulton DR, Kim MS ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com (Accessed on October 5, 2018).

 

 

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