Question

Indomethacin when given beyond 36 weeks what will happen?

• A. Premature closure of PDA
• B. Still birth
• C. No effect
• D. Teratogenic

Hint:

Recall which molecules maintain patency of the ductus arteriosus and what indomethacin does to their synthesis.

Answer 1

The Correct Option is A

Step 1: Recall the mechanism of action of Indomethacin.
Indomethacin is a non-selective NSAID (non-steroidal anti-inflammatory drug) that inhibits cyclooxygenase (COX-1 and COX-2) enzymes, thereby reducing prostaglandin synthesis. Prostaglandins -- specifically prostaglandin E2 (PGE2) and prostacyclin (PGI2) -- are critical for maintaining patency of the ductus arteriosus (DA) in the fetus.

Step 2: Understand the role of prostaglandins in the ductus arteriosus.
The ductus arteriosus is kept open (patent) in fetal life by the vasodilatory effect of prostaglandins, particularly PGE2. After birth, the rise in oxygen tension and fall in prostaglandins cause functional closure of the DA.

Step 3: Effect of indomethacin beyond 36 weeks.
When indomethacin is given after 36 weeks of gestation, it inhibits prostaglandin synthesis, reducing PGE2. This causes premature constriction (closure) of the ductus arteriosus in utero. This is actually the pharmacological basis for using indomethacin to close a patent ductus arteriosus (PDA) in preterm neonates. However, in a fetus beyond 36 weeks, this leads to premature in-utero closure of the DA, causing increased right ventricular afterload, tricuspid regurgitation, and potentially right heart failure in the fetus.

Step 4: Note on teratogenicity.
Indomethacin is not classically teratogenic (does not cause structural malformations). Its fetal effects are pharmacodynamic (related to its prostaglandin inhibition), not teratogenic.

Conclusion: The correct answer is Premature closure of PDA.