sustained vasoconstriction, vascular remodeling, in situ thrombosis
What are the mechanisms of PAH? (3)
prostacyclin, NO
Which mediators induce vasodilation? (2)
cGMP; cAMP
NO produces ________ & PGI2 produces ________; both of which result in vasodilation.
ET-1
What is the most potent vasoconstrictor?
sildenafil, tadalafil
What are the PDE5 inhibitors? (2)
-Prost suffix
What are the prostacyclin analogs?
selexipag
What is the prostacyclin agonist?
entan- suffix
What are the Endothelin receptor antagonists?
activates sGC---activating cGMP pathway, causing vasodilation and inhibition of proliferation
Inhaled NO MOA?
neonates, PAH diagnosis
Who is Inhaled NO indicated for? (2)
CYP3A4/2C9
Which enzymes metabolize PDE5 inhibitors? (2)
f; selective for PDE5
Sildenafil is a nonselective inhibitor of PDE5. T/F?
b
Which can cause blue-green tinting of vision?
a) tadalafil
b) sildenafil
c) riociguat
d) inhaled NO
a
Which has a longer half-life?
a) tadalafil
b) sildenafil
c
Which stimulates sGC independently of NO?
a) tadalafil
b) sildenafil
c) riociguat
d) inhaled NO
c
Which has a BBW for embryo-fetal toxicity?
a) tadalafil
b) sildenafil
c) riociguat
d) inhaled NO
localized actions; short half-lives
Prostacyclins have ________ & _________.
relax smooth muscle, inhibit platelet aggregation, increase BF & GFR in kidney
What are the physiological effects of Prostacyclin (PGI2)? (3)
decrease CA influx-prevent contraction; inhibit myosin light chain-relaxation; inhibit signaling cascades-antiproliferation
Prostacyclin agonists MOA? (3)
b
Which is inhaled?
a) selexipag
b) Illoprost
c) Epoprostenol
d) Treprostinil
a
Which is a prodrug?
a) selexipag
b) Illoprost
c) Epoprostenol
d) Treprostinil
a
Which has the longest half-life?
a) selexipag
b) Illoprost
c) Epoprostenol
d) Treprostinil
c
Which is a synthetic PGI2?
a) selexipag
b) Illoprost
c) Epoprostenol
d) Treprostinil
mitogen
-a small bioactive protein or peptide that induces a cell to begin cell division,
or enhances the rate of division (mitosis)
a
Primarily located on Vascular smooth muscle.
a) ET-A
b) ET-B
b
Primarily located on endothelial cells.
a) ET-A
b) ET-B
a
Which is most dominant?
a) ET-A
b) ET-B
a
Which is more selective for ET-A?
a) Ambrisentan
b) Macitentan
c) Bosentan
b,c
Which are equally selective for ET-A & ET-B?
a) Ambrisentan
b) Macitentan
c) Bosentan
b
Which has increased lipophilicity & receptor affinity?
a) Ambrisentan
b) Macitentan
c) Bosentan
pregnancy; teratogenic
The Endothelin Receptor Antagonists are contraindicated in ________
because of their _______ effects.
c
Which has the worst hepatotoxicity?
a) Ambrisentan
b) Macitentan
c) Bosentan
activin signaling inhibitor; reverses vascular remodeling
Sotatercept MOA?
TGF-B induces fibroblast/myofibroblast proliferation; causes ECM deposition that leads to scarred lung tissue
How does Pulmonary Fibrosis occur? (2)
inhibits TGF-B, TNF-a, & IL-1B
Pirfenidone MOA?
inhibits receptor Tyr-K by binding to ATP pocket; inhibits VEGFR and FGFR
Nintedenaib MOA?