Category: paracetamol

Choice of NSAID for closure of patent ductus arteriosus?

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.

Route of administration of N-acetylcysteine for paracetamol poisoning

In a clinical setting of paracetamol poisoning, how would N-acetylcysteine be administered to the patient? 

It is usually administered intravenously (IV). It is best administered within 8 hrs of paracetamol overdose, and dosing is maintained over the next 20 hrs.

Paracetamol for osteoarthritis or rheumatoid arthritis?

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.

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