A 62-year-old woman with pancreatic head cancer and obstructive jaundice presents with pruritus and steatorrhoea. She is awaiting palliative bilioenteric bypass. Which drug is the first-line choice to relieve her itching while awaiting surgical intervention?

Explanation

## Management of Pruritus in Obstructive Jaundice **Key Point:** Bile salt sequestrants (cholestyramine) are the first-line pharmacological treatment for cholestatic pruritus in obstructive jaundice. ### Mechanism of Pruritus in Obstructive Jaundice 1. Accumulation of bile salts in skin and serum 2. Bile salts activate pruritogenic pathways (TGR5, FXR receptors) 3. Elevated lysophosphatidic acid (LPA) and other pruritogens 4. Central and peripheral itch signalling amplified ### First-Line: Cholestyramine **Mechanism:** - Bile acid sequestrant (anion-exchange resin) - Binds bile salts in the intestinal lumen - Prevents enterohepatic circulation and reabsorption - Reduces serum bile salt concentration - Onset: 2–7 days **Dosing:** 4–8 g once or twice daily (before meals) **Advantage:** Effective, safe, minimal systemic absorption ### Stepwise Approach to Cholestatic Pruritus | Step | Agent | Indication | Notes | |------|-------|-----------|-------| | 1st line | Cholestyramine | All patients | Bile salt sequestrant; onset 2–7 days | | 2nd line | Ursodeoxycholic acid | If inadequate response | UDCA 13–15 mg/kg/day; slower onset | | 3rd line | Rifampicin | Refractory cases | 150–300 mg BD; induces bile acid metabolism; hepatotoxicity risk | | 4th line | Opioid antagonists (naltrexone) | Severe refractory pruritus | Off-label; limited evidence | | Adjunctive | Antihistamines | Symptomatic only | Do NOT use as monotherapy; minimal efficacy in cholestatic itch | **Clinical Pearl:** Antihistamines are ineffective for cholestatic pruritus because the itch is not histamine-mediated; they may help only if concurrent atopic dermatitis exists. **High-Yield:** In obstructive jaundice awaiting definitive decompression (ERCP, bypass, or resection), cholestyramine should be started immediately and continued until bile flow is restored. Steatorrhoea improves once the biliary obstruction is relieved. **Mnemonic: CURE for Cholestatic Pruritus** - **C**holestyramine (1st line) - **U**rsodeoxycholic acid (2nd line) - **R**ifampicin (3rd line) - **E**xperimental agents (naltrexone, sertraline)