Drugs for Pulmonary Arterial Hypertension Flashcards
What is the sign that pulmonary hypertension is occuring?
Elevated pulmonary arterial pressure and right ventricular failure.
Symptoms will include SOB, with extertion and slow progression to dyspnea.
What are the three general pathways of pulmonary artery hypertension?
NO cGMP - PDE5 pathway
Prostacyclin pathway
Endothelin pathway
What is the purpose of targeting Endothelin -1 in pulmonary aterial hypertension?
Endothelin 1 is a potent vasoconstrictor peptide produced by the vascular endothelium.
What are the different functonal effects of endothelin 1 receptors:
ETa and ETb?
ETA is expressed on vascular smooth muscle cells, when activated they increase release of intracellular Ca@+
ETb is on vascular endothelial cells where it leads to NO vasorelaxation. IT is also on vascular smooth muscle cells where it leads to vasoconstriction.
What occurs in endothelial dysfunction in PAH in regards to Endothelin?
Leads to a substantial increase in ET1 production and an over expression of ETa and ETb on VSMCs resulting in vasoconstriction.
eNOS is also inhibited blunting NO production.
How does the drug Bosentan work?
This drug is an endothelin receptor antagonist used in treatment of pulmonary artery hypertension.
It works by blocking endothelin receptors.
What is the contraindication of the drug Bosentan?
Pregnancy!
What function does prostacyclin have in the lungs?
Normally prostacyclin acts to provide vasodilation.
However in PAH, the endothelial lung cells are damaged and prostacyxlin is not released.
What is the suffix of the prostacyclin drugs?
These drugs all have the suffix “Prost”
and include:
Epoprostenol, Iloprost, and Treprostinil.
What is the use of prostacyclin analogue drugs?
These drugs work to improve prostacyclin production leading to vasodilation in pulmonary artery hypertension.
What is the indicated use for prostacyclin analogue drugs?
Used to prolong survival of those in need of lung or lung heart transplant.
Name the three prostacyclin analogues in order of half life
Epoprostenol 3-5 mins
Iloprost 30 min
Treprostinil 3-4 hours
Think of it alphabetically !
What is the purpose of targetting phosphodiesterase V in pulmonary artery hypertension?
Acts to block the breakdown of cGMP, this leads to increased calcium channels and ultimately pulmonary vasodilation!
What is the suffix of the Phosphodiesterase V inhibitors?
“Afil”
Sildenafil
and
Tadalafil
