2. Peters - PAH & Meds Flashcards
What are the four PAH groups of WHO class one PH
- Idiopathic
- Heritable
- Drug induced
- Misc.
PAH clinical definition
- A mean pulmonary artery pressure > 25mmHg at rest w/ a pulmonary wedge pressure or left ventricular end
3 Biological Mediators of PAH
- Prostacyclin - vasodilator and anti-Proliferative substance produced by endothelial cells –> levels are reduced in PAH
- Endothelin - vasoconstrictor produced in the endothelium that stimulates proliferation of pulmonary artery smooth muscle –> levels are increased in PAH
- Nitric Oxide - vasodilator produced from endothelium that inhibits platelet aggregation and vascular smooth muscle cell proliferation –> levels decreased in PAH
Signs and Symptoms of PAH
Exertional dyspnea, fatigue, weakness, exertional chest pain, general exertion tolerance, dyspnea at rest, syncope, lower extremity edema
3 Diagnosis
- Echocardiogram (TTE) - noninvasive, use to assess treatment, cannot be used for a definitive diagnosis
- Right Heart Catheterization - definitive diagnosis, pts given a vasodilator to see how it impacts PAH
- Exercise Capacity - 6 minute walk test, used to monitor
Nonpharm Treatment
- Management of comorbid conditions
- Pregnancy prevention
- Immunization
- Supervised exercise activity
- Supplemental oxygen
- Low-sodium diet (
Bosentan (Tracleer)
PO BID
Class: Endothelin Receptor Antagonist
MOA: block endothelin receptors on vascular endothelium & smooth muscle
AE: increase in liver function tests, anemia,
Misc: Black box warning - hepatotoxicity and pregnancy, improves exercise capacity, functional class, hemodynamics, only available though REMS program
Ambrisentan (Letairis)
PO QD
Class: Endothelin-Receptor Antagonists
MOA: block endothelin receptors on vascular endothelium & smooth muscle
AE: anemia,
Misc: Black box warning - idiopathic pulmonary fibrosis and pregnancy, improves exercise capacity, hemodynamics, only available though a REMS program, very rare liver toxicity
Macitentan (Opsumit)
PO QD
Class: Endothelin-Receptor Antagonist
MOA: block endothelin receptors on vascular endothelium & smooth muscle
AE: anemia
Misc: black box warning - pregnancy, only drug shown to reduce morbidity and mortality
Nitric Oxide (INOmax) Peds dosing
MOA: selectively dilates pulmonary vasculature when inhaled
AE: hypotension
Misc: vasodilator during vas reactivity trial, primary use is in peds
Epoprostenol (Flolan, Veletri)
Dosed IV
Class: Prostacyclin Derivative
MOA: synthetic analog of prostacyclin
AE: N/V/D is dose limiting
Misc: must be given as continuous IV (super short half life), increased risk of infection
Treprostinil (Remodulin, Tyvaso, Orenitram)
IV dosing
Class: Prostacyclin Derivative
MOA: synthetic analog of prostacyclin
AE: infusion site pain w/ subQ. inhaled-irritation, cough, headache. PO-headache, nausea, jaw pain
Misc: similar improvements and easier to use than epoprostenol
Iloprost (Ventavis)
Inhaled
Class: Prostacyclin Derivative
MOA: prostacyclin analog
AE: lock jaw, cough
Misc: inhalation dosing system, no risk of infections
Selexipag (Uptravi)
PO BID
Class: Prostacyclin Receptor Agonist
MOA: prostacyclin IP receptor agonist
AE: headache
Misc: high binding affinity for IP receptor, most recent agent
Sildenafil (Revatio)
PO TID
IV TID
Class: Phosphodiesterase-5 Inhibitor
MOA: increase intracellular conc of cyclic guanosine monophosphate leading to vasorelaxation and antiproliferative effects on vascular smooth muscle
AE: headache, flushing
Misc: reduce mPAP and improve functional class, contraindicated w/ concurrent nitrate therapy
