Pulmonary Arterial Hypertension Flashcards
What is PAH
High BP in pulmonary arteries from imbalance of vasoconstriction (↑TXA2, ↑endothelin1) & vasodilation (↓prostacyclin, ↓NO) → right ventricle HF Classified: Group 1 of Pulmonary Hypertension (PH) PAH = mPAP ≥ 25mmHg (Normal 8 -20)
S/Sx of PAH
Fatigue
Dyspnea
Chest pain
Syncope
Edema
Tachycardia
Non-pharm PAH tx
Sodium < 2.4g/day Vaccines: Flu, Pneumonia Avoid high altitudes O2 Sat > 90%
PAH Tx Algorithm
Initial Drug Tx: warfarin INR goal: 1.5-2.5, loop diuretics & digoxin Perform: Right heart catheterization (gold standard) + Acute Vasoreactive Test (IV epoprostenol or IV adenosine or Inhaled NO) *Responder: mPAP ↓10 & < 40 → Tx: CCB: dilt-, amlo, nifed- (NOT verap-) *Non-Responder/failed CCB: ≥ 1 vasodilator: Prostacyclin, ERA, PDE5i or sGC
Pulmonary Fibrosis
Scarred, damaged lung tissue. S/Sx: dyspnea, non-productive cough Causes: amiodarone, bleomycin, dronedarone, MTX Tx: DC offending drug, O2, pirfenidone (Esbriet), nintedanib (Ofeb): slows rate of decline in lung function. sildenafil (off-label
Flolan
Epoprostenol
Veletri
Epoprostenol
Remodulin
Treprostinil
Tyvaso
Treprostinil
Orenitram
Treprostinil
Ventavis
Iloprost
Uptravi
Selexipag
Prostacyclin Analogues ( Prostanoids)
Epoprostenol
Treprostinil
Iloprost
Selepaxig
Key features of Prostacyclin Analogues
MOA: Potent vasodilator + inhibit platelet aggregation
Notes: parenteral: most potent
epoprostenol: protect from light
Flolan: req ice packs for solution
Safety - Prostacyclin Analogues
ADR: Vasodilation reactions (Flushing), Jaw pain, Infusion-site pain Warning: Rebound PH (don’t ↓ dose or DC abruptly) Chronic IV infusions → Infections Avoid: Drugs that ↓prostaglandin (e.g., NSAIDs)
Endothelin Receptor Antagonists
Bosentan
Ambrisentan
Macitentan
Tracleer
Bosentan
Letairis
Ambrisentan
Opsumit
Macitentan
Endothelin Receptor Antagonist - Key features
MOA: Blocks vasoconstriction & proliferation effects
bosentan: ↓ effectiveness of contraceptives
Endothelin Receptor Antagonists - Safety
BBW: embryo-fetal toxicity (negative pregnancy test prior initiation; monthly thereafter),
bosentan: hepatotoxicity
C/I: pregnancy
ADR: HA, hepatotoxicity, ↓Hgb/Hct, fluid retention
**REMS** for all agents
PDE-5 inhibitors
Sildenafil
Tadalafil
Revatio
Sildenafil
Adcirca
Tadalafil
PDE-5 Inhibitor - Key features
MOA: PDE5i → ↑cGMP → pulmonary vasculature relaxation and vasodilation
PDE-5 Inhibitor - Safety
C/I: Use w/nitrates or riociguat
Warning: hearing/vision loss, NAION (nonarteritic anterior ischemic optic neuropathy), priapism, hypotension ADR: HA
Soluble Guanylate Cyclase Stimulator (sGC)
Riociguat
Adempas
Riociguat
Soluble Guanylate Cyclase Stimulator (sGC) - Key features
MOA: sensitizes sGC to endogenous NO and directly stimulates the receptor → ↑cGMP → relaxation and antiproliferative effects in pulmonary artery muscle cells
Soluble Guanylate Cyclase Stimulator (sGC) - Safety
BBW: embryo-fetal toxicity (negative pregnancy test prior initiation; monthly thereafter)
C/I: Pregnancy, use w/nitrates or PDE5i
ADR: hypotension, HA
**REMS**