Category: NSAIDs

NSAIDs increase risk of gastritis and gastric ulcers

What is the mechanism for NSAIDs leading to gastric ulcer formation? Can it also cause gastritis?

With high levels of acidity and digestive enzymes, and food movement, the stomach is an aggressive environment for the tissues lining the stomach wall. Prostaglandins mediate endogenous protective mechanisms, including (1) increased mucosal blood flow; (2) increased mucus secretion; (3) increased bicarbonate secretion; and, at high concentrations, (4) reduced acid secretion.

Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit the cyclo-oxygenase (COX) enzyme. COX is involved in the production of prostanoids, including classical prostaglandins. In the stomach, COX-1 is essential for the production of the protective prostaglandins. Therefore, inhibition of COX by NSAIDs increases the risk of gastritis (the general term for conditions involving inflammation of the lining of the stomach), including gastric ulcers.

Aspirin for prevention of preeclampsia

Non-steroidal anti-inflammatory drugs (NSAIDs) are contraindicated in the third trimester of pregnancy because of the risk of premature closure of the ductus arteriosus. So why is aspirin used to prevent preeclampsia?

Low-dose aspirin is used to prevent preeclampsia in women at high risk of developing preeclampsia. However, NSAIDs are known to promote closure of the ductus arteriosus (see Cyclooxygenase inhibitors for closure of the ductus arteriosus) and so are contraindicated in the third trimester of pregnancy.  So why is aspirin used to prevent preeclampsia?

Preeclampsia is associated with increased platelet turnover and increases in platelet-derived thromboxane levels. Low doses of aspirin once per day are sufficient to be antiplatelet and reduce thromboxane production by the platelets. Such low doses are unlikely likely to trigger closure of the ductus arteriousus and so are relatively safe even in the third trimester of pregnancy. Thus, for the women at high risk of preeclampsia the risk-to-benefit ratio is in favour of prescribing low-dose aspirin.

Additionally, it has been reported that preeclampsia is associated with exaggerated inflammatory responses. The anti-inflammatory actions of aspirin may therefore also be beneficial in preventing preeclampsia, although the low doses used would not produce a strong anti-inflammatory effect.

There remains debate over the optimal dose and the best time to start aspirin treatment. Typically, doses between 75 mg and 162 mg/day have been used started typically before 12 weeks of gestation and certainly before 16 weeks.

Reference:

August, P & Jeyabalan, A (2019) Preeclampsia: Prevention. Lockwood, CJ & Barss, VA ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com (Accessed on February 19, 2019).

Cyclooxygenase inhibitors for closure of the ductus arteriosus

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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