Pulmonary Artery Hypertension

Question 1

At what presssure can PAH be diagnosed?

Answer 1

> 20mmHg at rest

Question 2

What does pulmonary artery hypertension lead to in the arteries?

Answer 2

Arteriosclerosis

• Medial hypertrophy
• Intimal fibrosis of pulmonary arteries
• Plexiform lesions

Question 3

What inactivating gene mutation causes heritable PAH?

Answer 3

BMPR2

Question 4

How does a BMPR2 mutation lead to PAH?

Answer 4

BMPR2 usually inhibits vascular SM proliferation

- Endothelial dysfunction results in incr vasoconstrictors (e.g. endothelin) and decr vasodilators (NO, prostacyclins)

Question 5

What are other causes of PAH (outside of BMPR2 mutation)?

Answer 5

• Amphetamines, cocaine
• Connective tissue disease
• HIV infection
• Portal hypertension
• Congenital Heart disease
• Schistosomiasis

Question 6

What are the 3 different classes of drugs used to treat Pulmonary hypertension?

Answer 6

• Endothelin receptor (endothelin-1) antagonists (Bosentan)
• PDE5 inhibitors (sildenafil)
• Prostacyclin analogs (epoprostenol, iloprost)

Question 7

What is the MOA of PDE5 inhibitors (sildenafil)?

Answer 7

Inhibits PDE-5

• Increasing cGMP
• Prolonged vasodilatory effect of NO

Question 8

When are PDE5 inhibitors (sildenafil) contraindicated?

Answer 8

When taking nitroglycerin or other nitrates

- Risk of severe hypotension

Question 9

What is the MOA of Prostacyclin analogs (epoprostenol, iloprost)?

Answer 9

PGI2 (prostacyclin) with direct vasodilatory effects on pulmonary and systemic arterial vascular beds
- Inhibits platelet aggregation

Question 10

What are side effects of Prostacyclin analogs (epoprostenol, iloprost)?

Answer 10

• Flushing

- Jaw pain