Pulmonary Arterial HTN

Question 1

pulmonary arterial HTN (PAH):

A group of diseases distinguished by_1_ of the small pulmonary arteries with associated elevated pulmonary arterial pressure and_2_ failure.

Answer 1

1. vascular remodeling

2. right ventricular failure

Question 2

MOA of Bosentan

Answer 2

endothelin receptor antagonists

Nonselective receptor blocker, blocking both the initial vasodilatory response (ETB) and the sustained vasoconstrictive response (ETA)

Question 3

when is bosentan contraindicated

Answer 3

pregnancy

Question 4

what drug is a prostacyclin derivative for PAH

Answer 4

eroprostenol, iloprost, treprostinil

Question 5

MOA of eroprostenol, iloprost, treprostinil

Answer 5

Prostacyclin derivative approved for PAH

Prostacyclin produced by ECs causes vasorelaxation
Gs-coupled IP receptor –> increased cAMP
Endothelial dysfunction in PAH
Reduced PGI2 –> vasoconstriction

Question 6

PDE5 inhibitors

Answer 6

Sildenafil

Tadalafil

Question 7

MOA of Sildenafil and Tadalafil

Answer 7

inhibits phosphodiesterase type V (abundant in pulmonary vasculature) –> accumulation of cGMP –> sequestration of vascular smooth muscle Ca2+ –> pulmonary vasodilation –> decrease PAH

Question 8

SE of PAH drugs

Answer 8

flushing, nausea, diarrhea, hypotension

due to vasodilation

Question 9

do prostacycline derivatives or PDE5 inhibitors have longer T1/2

Answer 9

PDE5 inhibitors

Question 10

Effects of epoprostenol, iloprost, treprostinil

Answer 10

Improves symptoms, prolongs survival, delays/prevents the need for lung or lung-heart transplantation

Question 11

effects of SILDENAFIL, Tadalafil

Answer 11

reduces mean PA pressure, PA resistance; improves exercise capacity, prolongs survival, delays/prevents the need for lung or lung-heart transplantation