Therapeutics: IPAH

  1. What does IPAH stand for?
    • Idiopathic Pulmonary Arterial Hypertension
    • What qualifies a patient as having IPAH?
    •  mPAP >25 mmHg at rest or 30 mmHg under stress
    • Determined by Right heart catheterization (pulmonary vessels exit right heart)
  2. What is the cause of IPAH?
    • Shear stress (congenital Heart abnormality)
    • Viruses, Drugs
    • Infalmmation
    • Mutation
    • Autoimmunity (CREST, SLE
    • All cause Endothelial dysfunction and proliferation
  3. What are the pathological responses to IPAH?
    •  Smooth muscle hypertrophy (collapses onto vessel)
    •  Intima hyperplasia (narrowing)
    •  In-situ thrombosis (plaques)
  4. What is the Goal of therapy for IPAH?
    Prolong life, ↓progression and ↑ QOL = no hemodynamic goals
  5. What is the Focus of treatment for IPAH?
    • Open constricted vessels in the pulmonary system
    • What are the three general methods of treating IPAH?
    • Avoidance = reduce circulating mediatiors (Thromboxane, Serotonin, Platelets)
    • Endothelial-dependent factors = ↑ NO and prostacyclin, ↓endothelin and Thromboxane
    • Smooth muscle ion channel activity = Ca balance in cells (use CCBs to treat)
  6. What are the 5 WHO classes for PAH?
    • Group 1: idiopathic (IPAH), HIV, Portal Hypertension, congenital, newborn, drug/toxin induced
    • Group 2: Left heart disease = treat underlying disease
    • Group 3: lung disease or hypoxemia = treat underlying disease
    • Group 4: Chronic thromboembolic pulmonary hypertension = often recurrent PE = prevent PEs
    • Group 5: Unclear multifactorial = treat underlying diseases
  7. What are the general treatment focuses for the 5 WHO classes for PAH?
    • Group 1: Vasodilation
    • Group 2: Treat underlying disease
    • Group 3: Treat underlying disease
    • Group 4: Prevent PEs
    • Group 5: Treat underlying diseases 
  8. What are the IPAH function Classes?
    • Class 1: w/o physical limitation of dyspnea, fatigue, chest pain or presyncope
    • Class 2: Mild physical limitation during ordinary or excessive activity
    • Class 3: Marked limitation of physical activity, fine at rest.
    • Class 4: Inability to perform any activity w/o symptoms, symptoms at rest, signs of Right heart failure, JVD, accentuated heart sounds, edema
  9. Is IPAH progressive?
     Progressive, can be temporarily revert with treatment, but will eventually progress
  10. What are the Non-pharma treatments for IPAH?
     avoid strenuous activity(walking OK), pregnancy, ↑elevation (↓O2), infection 
  11. What drugs should be avoided w/ IPAH?
    • Vasoactive decongestants (phenyl-pseudoephrine)
    • Cardiodepressant antihypertensives (BBs)
    • Warfarin/Anticoag interacting drugs
  12. How do the doses for IPAH pharmacological treatment compare to normal doses?
    Usually much higher doses
  13. How do you deal with Tolerance to IPAH drugs?
    Increase dose or switch medication
  14. What drug has a mortality benefit for IPAH?
  15. What is the Goal INR for Warfarin use in IPAH?
  16. Why is Warfarin used in IPAH and not new anticoags Riva, Apix and Daba?
     Have not been studied but could be used
  17. Why do we need to anticoagulate IPAH patients?
    Risk of thrombus/emboli  from catherter(w/ epoprostenol) or physical inactivity, venous stasis/slowing
  18. How is a vasodilator challenge performed?
    Small doses of epoprostenol, adenosine or inhaled NO while under RH cath
  19. What indicates in a Positive vasodilator challenge?
    •  Decreased mPAP by 10mmHg
    • Increased or unchanged CO or CI
    • Unchanged Systemic Pressure
    • Unchanged O2 sat.
  20. What drugs would you try to use if you had a positive vasodilator challenge result?
    Vasodilators like Nifedipine and Diltiazem = higher likelihood of success
  21. What indicates in a Negative vasodilator challenge?
    • Increased or unchanged mPAP
    • Decreased CO or CI or O2 sat.
    • Decreased Systemic Pressure
    • Increased R atrial pressure
  22. What drugs would you avoid if you had a positive vasodilator challenge result?
    Vasodilators like Nifedipine and Diltiazem = lower likelihood of success
  23. What Vasodilators are available for IPAH?
    Diltizem, Nifedipine, Epoprostenol, Treprostinil, Bosentan (Tracleer), Macitentan (Opsumit), Ambrisentan (Letairis), Sildenafil (Revatio), Tadalafil (Adcirca)
  24. What class is Nifedipine & Diltiazem useful for treating?
    Class II: useful in 25-30% of patients
  25. How does tolerance develop to Nifedipine & Diltiazem in IPAH?
    High doses leads to tolerance
  26. Epoprostenol (Flolan) is what type of drug?
  27. What is the major con to Epoprostenol (Flolan)?
    t1/2 = 3-5 min, Continuous IV, Judicious education required
  28. How do you titrate Epoprostenol (Flolan)?
    Titrate 3-7 days, then each month
  29. What are the dose limiting SEs of Epoprostenol (Flolan)?
     Jaw pain, Hypotension, HA, N/V, Flushing (titrate to these, then reduce)
  30. Treprostinil (Remodulin) is what type of drug?
    Prostacyclin analogue
  31. What is the benefit of Treprostinil (Remodulin) over Epoprostenol (Flolan)?
    t1/2 = 3-4 hrs, stable at RT (no ice packing), Neutral pH
  32. What is the Dose for Treprostinil (Remodulin)?
     1.25 ng/kg/min to 40 ng/kg/min, IV or SQ
  33. What are the Endothelin-receptor antagonists: 
    • Bosentan (Tracleer)
    • Macitentan (Opsumit)
    • Ambrisentan (Letairis)
  34. What is the route of administration for Bosentan (Tracleer)?
  35. What is CI/NR for Bosentan (Tracleer)?
     Liver failure, CYP3A4 & 2C9 Inducer 
  36. What testing is required prior to Bosentan (Tracleer) use?
    Requires baseline liver test
  37. What is the Dose for Bosentan (Tracleer)?
     62.5mg BID for 4 weeks followed by 125mg BID
  38. What is the route of administration for Macitentan (Opsumit)?
  39. What is CI/NR for Macitentan (Opsumit)?
    • Pregnancy X (REM = restricted entity medical)
    • CYP3A4 substrate
  40. What is eth dose for Macitentan (Opsumit)?
    10 mg/day
  41. What is CI/NR for Ambrisentan (Letairis)?
    • Liver failure
    • CYP3A4 & 2C19 substrate
  42. What is the dose for Ambrisentan (Letairis)?
    5mg QD ↑ to 10mg QD
  43. What are the Phosphodiesterase type 5 inhibitors for IPAH?
    • Sildenafil (Revatio)
    • Tadalafil (Adcirca)
  44. What is the route of administration for Sildenafil (Revatio)?
  45. Which IPAH drugs are FDA approved for PAH?
    • Sildenafil (Revatio)
    • Tadalafil (Adcirca)
  46. What class is Tadalafil (Adcirca) and Sildenafil (Revatio) used for?
    Class II-III
  47.  What is the dosae for Sildenafil (Revatio)?
    20 mg TID, useful in combo
  48. What are the SEs for Sildenafil (Revatio)?
     HYPOtension, don’t use w/ Nitrates
  49. What is the route of administration for Tadalafil (Adcirca)?
  50. What is the dose for Tadalafil (Adcirca)?
     40 mg QD (Better than Sildenafil, which is TID), useful in combo
  51. Iloprost is mainly used for what?
    Neonates b/c requires constant inhalation
  52. At what point would you consider Combos for IPAH?
    • Stage III or IV
    • Single drugs not effective anymore
  53. What is the first thing all IPAH patients should be placed on?
    1st: Oral anticoagulant
  54. After an oral anticoagulant has been given, what is the second thing IPAH patients should have done?
    2nd: Vasodilator challenge 
  55. What would you give an IPAH patient after a Positive Response?
    Oral CCB
  56. What would you give an FC II IPAH patient after a Negative Response? 
    Ambrisentan, Bosentan, Sildenafil, Tadalafil
  57. What would you give an FC III IPAH patient after a Negative Response? 
    Ambrisentan, Bosentan, Epoprostenol IV, Iloprost Inh, Sildenafil, Tadalafil
  58. What would you give an FCIV IPAH patient after a Negative Response? 
    Epoprostenol IV, Iloprost Inh, Treprostinil SC, Treprostinil IV, Ambrisentan, Bosentan, Sildenafil, Tadalafil
  59. What would you give a patient with no improvement at FCIII or FCIV after all treatment options have been tried?
    Combo therapy of Prostanoid, ERA or PDE-5 Inhibitor
Card Set
Therapeutics: IPAH
Therapeutics: IPAH