Question

Which of the following drugs is known to cause retroperitoneal fibrosis?

• A. Methysergide
• B. Metformin
• C. Amlodipine
• D. Propranolol

Hint:

This ergot derivative used for migraine prophylaxis is the classic drug associated with retroperitoneal fibrosis.

Answer 1

The Correct Option is A

Retroperitoneal fibrosis (RPF) is a high-yield NEET PG topic in pharmacology adverse effects.

Prototype drug: Methysergide
Methysergide is an ergot alkaloid derivative used in migraine prophylaxis. It is the classic drug causing drug-induced RPF. It is a partial agonist at 5-HT2A/2B receptors and an antagonist at 5-HT2C receptors.

Mechanism of fibrosis:
5-HT2B receptor agonism activates fibroblasts and promotes collagen deposition in the retroperitoneal space, leading to progressive fibrosis encasing the ureters and great vessels.

Clinical features of RPF:
- Dull back/flank pain
- Hydronephrosis and renal failure (ureteral obstruction)
- Lower limb edema (venous/lymphatic compression)

Other drugs causing RPF:
- Ergotamine (ergot class)
- Pergolide and cabergoline (dopamine agonists -- 5-HT2B agonism)
- Beta-blockers (atenolol, propranolol -- rare association)
- Hydralazine, methyldopa

Prevention:
Drug holiday of 1 month for every 6 months of methysergide therapy is recommended.

Memory tip: $\text{Methysergide} \rightarrow \text{Retroperitoneal Fibrosis}$ (also causes pleuropulmonary and endocardial fibrosis)

\[\boxed{\text{Methysergide}}\]