Note Nov 11, 2024 (3) 2

Page 1: Introduction

  • Therapeutics of Cirrhosis

    • Soon Hye Yang, MS, PharmD, BCPS

    • Assistant Professor, College of Pharmacy, Department of Clinical & Administrative Sciences, Larkin University

Page 2: Objectives

  • Discuss treatment therapies for cirrhosis and common complications:

    • Portal hypertension and variceal bleeding

    • Ascites and spontaneous bacterial peritonitis

    • Hepatic encephalopathy

    • Hepatorenal syndrome

    • Coagulopathy

    • Alcoholic liver disease

  • Given a patient case, recommend appropriate treatments for complications of cirrhosis.

Page 3: Primary Prophylaxis: β-adrenergic Blockade

  • Mainstay of primary prophylaxis includes nonselective β-adrenergic blocking agents:

    • Examples: Propranolol, Nadolol, Carvedilol

  • Mechanisms of action:

    • Decrease cardiac output (β1 blockade)

    • Decrease splanchnic blood flow (β2 blockade)

  • Indications:

    • Patients with small varices, no history of bleeding, but at increased risk

    • (Child-Pugh Class B or C, red wall marks on varices)

  • Lifelong treatment with weekly titration to achieve either:

    • Heart rate of 55-60 bpm or

    • 25% reduction from baseline heart rate.

Page 4: Management of Moderate/Large Varices

  • Recommended therapy: for portal hypertension

    • Propranolol: 20-40 mg orally twice daily

      • Maximal daily dose 320 mg.

    • Nadolol: 20-40 mg orally once daily

    • Carvedilol: Start with 6.25 mg once daily, max 12.5 mg/day.

    • Endoscopic variceal ligation (EVL): every 2-8 weeks until eradication.

  • Therapeutic goals:

    • Maintain systolic blood pressure >90 mm Hg.

    • HR 55-60


Page 5: Endoscopic Variceal Ligation (EVL)

  • EVL involves placing rubber bands around varices to obliterate them.

  • Does NOT improve survival

  • EVL is intolerant to BB or contraindication:

    • Examples of contraindications:

      • bradycardia

      • heart block

      • uncompensated heart failure

      • severe asthma

      • Diabetes Type 1

      • Pregnancy 2nd/3rd

      • Peripheral Vascular Disease

Page 6: Treatment of Acute Variceal Hemorrhage

  • Initial management:

    • Fluid resuscitation, maintain hemoglobin ~8 g/dL.

  • Combination pharmacological therapy:

    • Endoscopic variceal band ligation (EGD within 12 hours).

      • Administer erythromycin IV before endoscopy.

    • Use vasoactive drugs (e.g., Octreotide).

    • Prophylactic antibiotics :

      • Ceftriaxone,

      • Ciprofloxacin

      • Bactrim

  • Fluid Resuscitation and Hemodynamic Stabilization

    • MaintainHbconcentrationatabout8g/dL
    •Administration of fresh frozen plasma or platelets may be considered for patients with considerable coagulopathy





Page 7: Octreotide in Acute Variceal Hemorrhage

  • Mechanism:

    • Selective vasoconstriction of mesenteric circulation, reducing splanchnic blood flow.

    • Used in combination with endoscopic procedure

  • Dosing:

    • Octreotide 50 mcg IV bolus, followed by 50 mcg/h for 3-5 days.

  • Side effects include hyperglycemia and abdominal cramping.

Page 8: Secondary Prophylaxis (Prevention)

  • For patients with a history of variceal bleeding:

    • Endoscopic band ligation & nonselective β-blocker (e.g., Propranolol, Nadolol).

  • Secondary prophylaxis should start post vasoactive drug therapy ending (ASAP).

  • Associated with reduced incidence of variceal rebleeding.

Page 9: Treatments for Prevention of Recurrent Esophageal Variceal Hemorrhage

  • Recommended dosages for therapies:

    • Propranolol and Nadolol with similar follow-up considerations as previously outlined.

    • EVL: every 1-4 weeks until eradication of varices.

  • Combination platelet therapy is recommended.

Page 10: Management of Ascites

  • Objectives of ascites management include:

    • Control ascites

    • Relieve symptoms

    • Prevent life-threatening complications

      • (e.g., SPB, hepatorenal syndrome).

Page 11: Goals of Therapy for Ascites

  • Calculate Serum-Ascites Albumin Gradient (SAAG): SAAG = serum albumin – ascitic fluid albumin.

  • If SAAG ≥ 1.1 g/dL

    • Ascites is likely secondary to portal hypertension responding to treatment.

  • If SAAG < 1.1 g/dL,

    • treatment is less likely effective.

Page 12: Treatment of Ascites

  • Key elements of treatment include:

    • Alcohol abstinence

    • Sodium restriction (< 2g/day)

    • Fluid restriction if serum sodium <120-125 mmol/L.

  • Diuretics:

    • Spironolactone (inhibits aldosterone) with specific dosing strategies.

    • In cirrhotic patients, antagonize the excessive reabsorption of sodium in the kidney from increased aldosterone

    • Spironolactone PK: metabolized to an active metabolite, canrenone which is also metabolized and has a half-life of 13-26 hours. Need to titrate spironolactone slowly every 5-7 days.


Page 13: Spironolactone Dosing for Ascites

  • Based on urine sodium:pottassium ratio:

    • Start at 200 mg/day (high aldosterone) if <1.0.

    • Start at 50 mg/day (low aldosterone) if >1.0.

  • Titration and combination therapy with furosemide are critical.

  • Titrate using 100 mg : 40 mg ratio to max doses of 400 mg/160

    • prevent hyper or hypokalemia, achieve rapid natiruertic effect