(6.1) Pulmonary Hypertension (Wolff) Flashcards
What are the (4) prostanoids?
-prost
Epoprostenol
Treprostinil
Iloprost
Selexipag
What are the (2) PDE 5 inhibitors?
-afil
Sildenafil
Tadalafil
What are the (3) endothelin antagonists?
-sentan
Bosentan
Ambrisentan
Macicentan
What is the (1) guanylate cyclase sensitizer?
Riociguat
If you get a positive CCB vasopressor test…
What drugs do you use?
Nifedipine
Diltiazem
Amlodipine
What is the primary target for the drugs we are learning for this lecture?
Pulmonary aterial hypertension (PAH)
What is the definition of PAH?
Sustained elevation of mean pulmonary arterial pressure (mPAP) is
greater than or equal to 25mmHg at rest
What is the normal pulmonary pressure?
14 plus or minus 3 mmHg
What population is typically affected by pulmonary HTN?
Young women
What is pulmonary arterial hypertension (PAH) characterized by?
Progressive increase in pulmonary vascular resistance (PVR)
What does PAH eventually lead to (anatomically)?
Right ventricular overload –> right ventricular failure = premature death
What are the EARLY symptoms of PAH?
Dyspnea upon exertion
Fatigue
Chest pain
Tachycardia
Pain on the upper right side of the abdomen
Anorexia
What are the LATE symptoms of PAH?
Syncope
Swelling in legs and ankles
Cyanotic lips and skin
What is a MAJOR genetic correlation to produce PAH?
BMPR2
What is a MAJOR drug that can predispose pts to PAH?
Fenfluramine/phentermine
“fen/phen” weight loss pill
What are key components (ligands) involved in pulmonary vascular remodeling?
5-HT
ET-1
What is the gold standard for measuring pulmonary pressure?
Right heart catheterization
What is the MOA for epoprostenol?
Mimics the actions of endogenous prostacyclin
(endogenous prostacyclin is a compound that promotes vascular relaxation)
Noteworthy about epoprostenol?
VERY SHORT HALF LIFE!!!
(6 min)
Must be given by continuous IV
What are the toxicities associated with epoprostenol?
Sepsis due to chronic catheter
Life threatening problems if pump lines become clogged
Common side effects = N/V, Headace, flushing jaw pain
Since epoprostenol wasn’t great…came out with another drug that has the same MOA, but has a few differences in the pharmacokinetics…
What drugs am I talking about?
Treprostinil
What is unique about the pharmacokinetics of treprostinil?
SubQ infusion with a LOT of pain
Higher half life (4hrs) than epoprostenol
Doesn’t require refrigeration
Same MOA as both epoprestenol and treprostinil… slightly different pharmacokinetics and toxicities…
What drug am I talking about?
Iloprost
What are the unique pharmacokinetics of iloprost?
Administered via INHALATION
What are the side effects of Iloprost?
Fainting due to hypotension
Cough, headache, flushing, jaw pain
Since epoprostenol, treprostinil, iloprost all had some bad qualities to them, came out with another drug that is an oral medication used to treat PAH.
What drug am I talking about?
Selexipag
What is the major downside to using selexipag?
SUPER EXPENSIVE
$225 per pill
What is the MOA of bosentan?
Nonspecifically blocks the ETA and ETB endothelin receptors
What are the side effects associated with bosentan?
Hepatotoxicity
Teratogenesis
What are the noteable drug interactions with bosentan?
ORAL CONTRACEPTIVES
Warfarin
What is the MOA of ambrisentan?
SELECTIVELY blocks the ETA receptors
What are the advantages and disadvantages of using ambrisentan?
Disadvantage: SUPER expensive, teratogenesis
Advantages: Does not damage liver, does not interfer with warfarin or oral contraceptives
MOA of sildenafil?
Selectively blocks phosphodiesterase type V
What is the MOA of riociguat?
Dual mode of action:
1) Sensitizes soluble guanylate cyclase (sGC) to endogenous nitric oxide (NO)
2) Directly stimulates sGC independent of NO
(Together, the increased generation of cGMP leads to increased vasodilation)
