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Therapeutics: Portal HTN

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  1. What is normal Hepatic venous pressure?
    1-5 mmHg
  2. What is elevated Hepatic venous pressure?
    > or = to 6
  3. What HVPG level is associated with the highest risk of variceal bleeding?
    > or = to 12 mm Hg
  4. What HVPG level is associated with the highest risk of mortality?
    > or = to 16 mm Hg
  5. What HVPG level is associated with the highest risk of mortality?
    > or = to 30 mm Hg
  6. What are the Clinical Manifestations of Cirrhosis?
    • Hepatic Encephalopathy
    • Ascites
    • Portal Hypertension
    • Jaundice & spider angiomata
    • Gynecomastia
    • Decreased blood pressure
    • Hepatomegaly
    • Lab abnormalities
    • Thrombocytompenia (PLT <100)
    • Encephalopathy
    • Ascites
  7. What three characteristics have the highest predictive value for Cirrhosis?
    • Thrombocytompenia (PLT <100)
    • Encephalopathy
    • Ascites
  8. What are the characteristics used to determine a child Pugh score?
    • Albumin
    • Acites
    • Bilirubin
    • Prothrombin time
    • Encephalopathy
  9. What are the Child-Pugh scores?
    A, B and C
  10. What is the MOA for Lactulose in Hepatic encephalopathy?
    • Removes ammonia and ammonia precursors from the gut
    • Is broken down into C02 and organic acids, lowering the Gut pH and causing the following:
    • Ammonia to move from the gut to the GI
    • NH4 formation and thus increased excretion
    • Inhibition of urease producing bacteria in the GI
  11. What is the maintenance dose of Lactulose?
    • 20-30 grams PO TID or QID
    • Until 2-3 soft stools are produced per day
    • Minimum = 60 grams /day
  12. What is the Acute dosing for Lactulose?
    • 20-30 grams Q1-2H until 2-3 soft stools are produced a day
    • 300 mL rectal syrup enema retained for .5-1H Q4-6H
  13. How long should you wait to check Ammonia levels after Lactulose initiation?
    > 24 hours
  14. What is the main treatment for Hepatic encephalopathy?
    Lactulose
  15. Why would you not want to use Neomycin as an antibiotic therapy for Hepatic Encephalopathy?
    Aminoglycoside that can cause renal insufficiency
  16. What is the best add on therapy for Lactulose?
    Antibiotic: Rifaximin 550 mg BID
  17. What is the dose for Rifaximin antibiotic therapy for Hepatic Encephalopathy?
    550 mg BID
  18. Do you dose adjust for liver disease with Rifaximin?
    No, even though it increases AUC 10x
  19. Why would you avoid Metronidazole and Vancomycin in Hepatic encephalopathy?
    • Metronidazole can lead to disulfarin like reaction and cause vomiting if the person is still drinking
    • Vancomyocin and Metronidazole are the only real treatments for C. diff (don’t want o breed resistance)
  20. What are the secondary treatment options for Hepatic encephalopathy?
    • Flumazenil
    • Sodium Benzoate
    • L-carnitine
    • Memantine
  21. What is the MOA of Flumazenil in Hepatic encephalopathy?
    GABA antagonist
  22. What is the MOA of L-carnitine Hepatic encephalopathy?
    Protective effect against neurotoxicity
  23. What si the MOA of Memantine (Namenda) in Hepatic encephalopathy?
    NMDA receptor antagonist
  24. What are the complications of Portal HTN?
    • Ascites
    • Splenomegaly
    • Thrombocytopenia
    • Formation of portal-systemic collateral vessels
    • Bleeding esophageal varices
    • Bleeding gastric varices
    • Hepatorenal syndrome
    • Hepatopulmonary syndrome
    • Spontaneous Bacterial Peritonitis (SBP)
  25. Define Ascites:
    Accumulation of fluid in the retroperitoneal space
  26. What are the treatment options for Ascites?
    • Peritoneal tap (severe cases)
    • Na restriction (< 2g/day)
    • Fluid restriction (if Na <120)
    • D/C drugs that decrease renal perfusion: NSAIDs, ACEIs/ARBs and Propofol (the last on only if refractory)
    • Loop + K sparing diuretic (1st line)
  27. What is the desired ratio for Spirolactone to Furosemide in ascites treatment?
    • Spirolactone: Furosemide
    • 10:4
  28. What are the appropriate doses for Spirolactone and Furosemide in the treatment of ascites?
    • Spiro: 100-400 mg/day
    • Lasix: 40-160 mg/day
  29. If a patient is refractory to Furosemide treatment of Ascites, what can be used?
    • Torsemide (2x potent)
    • Bumetinide (40x potent)
  30. If a patient has gynecomastia on spirolactone, what drugs might you switch to?
    Eplerenone or Amiloride
  31. Can thiazide diuretics be used for Ascites?
    No, has to be a loop or a loop with a K sparing
  32. What patient parameters would make you D/C your diuretics in ascites?
    • Encephaolopathy continues
    • Hyponatremia continues despite fluid restriction
    • Renal insufficnecy (SCr >2 mg/dL)
  33. After paracentisis, what treatment should be administered if we remove more than 5 liters (in ascites)
    • Give Albumin
    • To avoid throwing off the circulatory system that has adapted to the ascites
  34. When would we treat a patient with Spontaneous bacterial peritonitis?
    • PMN = >250 cells/mm3
    • Or
    • PMN < 250 w/ symptoms
  35. Ascites can lead to what complications?
    • Spontaneous bacterial peritonitis
    • SOB//respiratory failure
  36. What patients would you consider SBP prophylaxis in?
    • Low protein ascites fluid
    • Hx of SBP
    • GI hemorrhage
    • Elevated serum bilirubin
  37. What would you use for prophylaxis of SBP with ascites?
    • Quinolone (-floxacin)
    • Bactrim (SMZ/TMP)
  38. What are the options for treating Esophageal and gastric varies in a portal HTN patient?
    • Non-selective BBs
    • Most studied: Porpranolol, nadolol and timolol
    • Propranolol and Nadolol are most commonly used
  39. If a patient cannot tolerate BB therapy for varices, what would their next treatment option be?
    Endoscopic Band Ligation (EBL)
  40. If a patient does not have esophageal varices, would you treat them prophylactically?
    Yes, very common to give BBs prophylactically
  41. What are the dosing guidelines for varices prophylaxis?
    • Start at the lowest dose
    • Titrate to max tolerated
    • Goal: 20-25% of HR or HR of 55-60
  42. What is the main drug therapy for variceal bleeding?
    • Octreonide 50-100 mcg bolus
    • Followed by 25-50 mcg/hr drip
  43. What is the MOA of Octreonide in treatment of variceal bleeding?
    • Decreases splancnic blood flow
    • Decreases portal inflow
    • Inhibits vasodilatory GI peptides
  44. What are the various drug therapies for variceal bleeds?
    • Octreonide
    • Vasopressin (w/ or w/o NO)
    • Prophylactic antibiotic therapy
  45. Why is Vasopression not a first line treatment for Variceal bleeding?
    Adverse effects
  46. What is the MOA of antibiotic therapy in Variceal bleeding?
    Prevent sepsis, especially if there are s/s of ascites
  47. What are the pharmacological options for secondary prophylaxis of variceal bleeding?
    • Non-selective BB
    • Long acting nitrate w/ or w/o a BB (isosorbide dinitrate/mononitrate)
  48. What is the goal for BB and long acting nitrate therapy for secondary prophylaxis of variceal bleed?
    Portal pressure gradient of: < 12 mm Hg
  49. The treatment for variceal bleed is the same for primary and secondary treatment, which is it more efficacious for?
    More evidence for Secondary
  50. What is the treatment regimen for Hepatorenal syndrome?
    • NE drip or vasopressin = to increase MABP
    • Albumin = pull fluid from 3rd space
    • Midodrine = alpha 1 agonist systemic vasoconstricotr
    • Octreonide = splanicnic vessel vasoconstrictor
  51. What is the goal of therapy for Hepatorenal sysndrome?
    • Decrease MABP
    • Decrease SCr to less than or = to 1.5
  52. Why would you switch from NE to Vasopressin in Hepatorenal syndrome?
    • Vasopressin will not increase HR like NE
    • If tachycardia is too high, would want to switch
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kyleannkelsey
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Therapeutics: Portal HTN
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Therapeutics: Portal HTN
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