Epidemiology

Etiology

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Idiopathic
Hereditary (e.g., BMPR2 loss-of-function mutation)
- Encodes a set of inhibitors of vascular smooth muscle cell proliferation
- Associated with a poor prognosis
Drug-induced
- Methamphetamine (and possibly amphetamines and cocaine)
Associated conditions
- Connective tissue diseases, e.g., systemic sclerosis
- Portopulmonary hypertension
- Congenital heart disease (e.g., left-to-right shunt, Eisenmenger syndrome)
- HIV infection
- Schistosomiasis

Calcium channel blockers: First-line pulmonary vasodilator therapy for patients with PAH and positive vasoreactivity testing
Other pulmonary vasodilator therapies: typically second-line agents, the choice of which depends on symptom severity
- Endothelin receptor antagonists (e.g., bosentan, macitentan, ambrisentan)
  - Competitively inhibit endothelin-1 receptors → ↓ vasoconstriction in the pulmonary circuit
- Phosphodiesterase-5 inhibitors (e.g., sildenafil)
  - PDE5 inhibition → ↓ breakdown of cGMP → pulmonary vasodilation, penile smooth muscle relaxation, and ↑ blood flow
- Prostacyclin analogs (iloprost, treprostinil) OR Synthetic prostacyclin (epoprostenol)
  - Prostacyclin (PGI2) acts as a direct vasodilator (systemic and pulmonary) and inhibits platelet aggregation via prostacyclin receptors.
  - Receptor binding of prostacyclins or prostacyclin analogs → ↑ intracellular cAMP → inhibition of myosin light chain kinase → vascular smooth muscle relaxation