Obeticholic Acid (OCA) Lecture Notes

Jun 23, 2024

Lecture Notes: Obeticholic Acid (OCA)

Introduction

  • Drug: Obeticholic acid (OCA)
  • Class: Farnesoid X receptor agonist
  • Function: Reduces bile acid levels in hepatocytes
  • Derived from: Chenodeoxycolic acid (secondary bile acid)

Mechanism of Action

  • Bile Acids and Receptors
    • Acts on farnesoid X receptors (FXR)
    • Reduces hepatic apoptosis and cirrhosis
  • Primary Biliary Cholangitis (PBC)
    • Condition involving increased gallstones and decreased biliary flow leading to cholestasis and inflammation
    • OCA reduces bile acid levels, used in PBC treatment

Usage

  • Combination with UDCA: Ursodeoxycholic acid (often used for PBC)
  • Patient Sensitivity: Should be given to patients who do not tolerate UDCA
  • Hepatic Decompensation: OCA should be restricted to avoid severe hepatic effects

Chemical Nature

  • Structure: Cholan-24-oic acid; 3,7-Dihydroxy; 6 alpha-ethyl
  • Synthesis Pathway: Cholesterol → Bile acids (mediated by CYP7A1)

Transporters Affected

  • NTCP: Sodium taurocholate co-transporting polypeptide (uptake of bile acids)
  • BSEP: Bile salt export pump (secretion of bile acids)
  • ASBT: Apical sodium bile acid transporter (absorption of bile acids)
  • Effects:
    • Inhibits NTCP (reduces bile acid uptake)
    • Promotes BSEP (increases bile acid secretion)
    • Inhibits ASBT (reduces bile acid absorption)
    • Induces FGF19 (fibroblast growth factor 19), further reducing bile acid synthesis

Precautions

  • Hepatic Issues: Can cause hepatic decompensation
  • Symptoms to Watch: Jaundice, ascites, GI bleeding
  • Pruritus: Severe itching causing sleep disturbance
  • HDL Cholesterol: Can decrease HDL levels, increasing cardiovascular risks

Side Effects

  • Common Side Effects:
    • Abdominal pain, fatigue, arthralgia (joint pain)
    • Pruritus (itching), dizziness, constipation
    • Eczema, peripheral edema, palpitations, pyrexia (fever)

Dosage

  • Form: Tablets (5 mg and 10 mg)
  • Initial Dose: 5 mg once daily
  • Increased Dose: Can be increased to 10 mg once daily after 3 months
  • Hepatic Dysfunction: Reduce to 5 mg once weekly

Summary

  • Effectiveness: Reduces hepatic apoptosis and biliary cirrhosis by affecting bile acid levels and transporters
  • Combination with UDCA: Enhances efficacy of PBC treatment
  • Careful Use: Needed in patients with hepatic decompensation

Conclusion

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