PAH (exam 3) Flashcards
pulmonary arterial hypertension
high blood pressure in the lungs
In PAH, increased pressure in the vessels is caused by
obstruction in the small arteries in the lungs
what kind of heart failure does PAH cause?
right sided HF
group 1 PAH
pulmonary arterial hypertension
group 2 PAH
PH due to left heart disease
group 3 PAH
PH due to lung disease and/or chronic hypoxia
group 4 PAH
PH due to blood clots in the lungs
group 5 PAH
PH due to blood and other disorders (sickle cell disease)
____________ use during pregnancy increases the risk of _________ PAH
SSRI
newborn
disorders associated with PAH
connective tissue diseases (scleroderma)
liver disease
HIV
congenital heart disease
drugs associated with PAH
stimulant use drugs (methamphetamine, cocaine, weight loss stimulants)
main symptoms of PAH
exertional dyspnea
fatigue that progressively worsens
as the disease progresses, symptoms of ____________ dysfunction and failure are present. these include:
right heart
dyspnea at rest, low extremity edema, chest pain, and syncope
what is required for definitive diagnosis of PAH?
pulmonary artery catheterization
normal pulmonary arterial pressure
25/10 mmHg (mean PAP of 15 mmHg)
In PAH, the PAP increases to around ______________
PAH is diagnosed if mean PAP is
4-/20 mmHg
greater than or equal to 25 mmHg
mean PAP =
1/3(systolic PAP) + 2/3(diastolic PAP)
PAH arises from changes in the
small pulmonary arteries and arterioles (effects PVR)
major cause of mortality of PAH
right side HF
In pulmonary HTN, there is an increase in ____________ for the right side of the heart
overtime this increased pressure leads to _____________-
afterload
Right ventricles dysfunction and right heart failure
can respiratory failure occur in PAH
yes
major pathogenic components in the development of PAH
sustained vasoconstriction
pulmonary vascular remodeling
in situ thrombosis
vascular wall stiffening
PAH functional class I
no symptoms/functional limitation
PAH functional class II
slight limitation of physical activity
PAH functional class III
marked limitation of physical activity
PAH functional class IV
symptoms with any activity or at rest
lifestyle modifications for PAH
sodium restricted diet
avoidance of high altitude
patients at risk for VTE should receive
warfarin
patients with fluid overload should receive
a loop diuretic
when is oxygen treatment required in PAH?
when oxygen saturation is below 90%
commonly used vasodilatory CCBs can be used to treat PAH?
long acting nifedipine
sustained release diltiazem
amlodipine
which vasodilatory CCB should not be used in PAH?
verapamil
CCBs are ineffective in PAH when
there is significant stiffening of the pulmonary arteries
Targeted therapies for patients who can’t take CCBs
Prostacyclin receptor agonists
endothelia receptor antagonists
PDE5 inhibitors
sGC stimulator
targeted therapies cause
vasodilation, reduce vascular remodeling and reduce platelet activation
Prostacyclin receptor agonists (prostanoids) examples
epoprostenol (Flolan)
Treprostinil (Tyvaso)
Iloprost (Ventavis)
Selexipag (Uptravi)
endothelial receptor antagonists
Bosentan (Tracleer)
Ambrisentan (Letairis)
Macitentan (Opsumit)
PDE5 inhibitors examples
sildenafil (Revatio)
tadalafil (adcirca)
sGC stimulator example
Riociguat (Adempas)
PAH class I patients should receive
mono therapy or no therapy
PAH class II-III patients should receive
combination therapy
PAH class IV patients should receive
combination therapy with a parenteral prostacyclin receptor agonist
prostacyclin receptor agonist MOA
activate the IP receptor (Gs coupled) which increases CAMP and reduce calcium
leads to vasodilation, reduced platelet activation and reduced vascular remodeling
In PAH, there is a reduction in which prostaglandin?
PGI2
Prostacyclin (PGI2)
released by vascular endothelial cells
maintain homeostasis
physiological antagonist of TxA2
Epoprostenol
synthetic form of PGI2
given continuous infusion via pump
1/2 life: 3-5 min
Treprostinil
given IV/SC infusion, inhaled or oral
longer half life that epoprostenol
Iloprost
given by inhalation
longest half life
Selexipag
not structurally related to PGI2
has an active metabolite
oral
active metabolite of selexipag
ACT-333679
ADRs of prostacyclin receptor agonists
pain
hypotension
GI
cough (if given inhalation)
treprostinil and selexipag are metabolized by
CYP2C8
prostacyclin receptor agonists have to be ____________ due to the chance of _________________ with sudden discontinuation
titrated up
rebound PAH
which prostacyclin receptor agonist is recommended in stage IV PAH
IV epoprostenol
endothelin I primarily bind to the _______ receptor and causes ______________
ETA
vasoconstriction
In PAH, there is up to a ____________ in plasma endothelin-1 and level of elevation correlates with _________________
10x increase
severity of disease
MOA of endothelin receptor antagonists
block the ETA receptor (Gq coupled) which reduces IP3, DAG and calcium
leads to vasodilation, reduced platelet activation and reduced vascular remodeling
ambrisentan
selectively blocks ETA receptor
Bonsentan and Macitentan
blocks both ETA and ETB receptors (higher affinity for A)
ADRs of endothelin receptor antagonists
hypotension
peripheral edema
anemia
increased liver enzymes
how does endothelin receptor antagonists increase liver enzymes?
drug metabolites compete with bile acids for binary excretion causes bile build up
bosentan induces
CYP3A4 and 2C9
endothelin receptor antagonists are contraindicated in
pregnancy
bonsetan has a BBW for
hepatotoxicity
endothelin receptor antagonists have to go through the ________ program due to their BBW for ______________
REMS
skull and facial abnormalities in fetus and CV malformation
In PAH a reduction in synthesis of ___________ occurs leading to a reduction in cGMP
nitric oxide
guanylate cyclase converts
GTP to cGMP
PDE5
enzyme that breaks down cGMP to inactive GMP
example of medications that increase cGMP
PDE5 inhibitors
sGC stimulator
ADRs of PDE5 inhibitors
hypotension
myalgia (tadalafil)
dose dependent visual disturbance
PDE5 inhibitors are metabolized by
CYP3A4
PDE5 inhibitors should not be used in combination with
nitrates or riociguat
sGC stimulator MOA
directly stimulates soluble guanylate cyclase and increases binding of nitric oxide to sGC
ADRs of sGC stimulator
hypotension
GI
anemia
hemorrhage
riociguat is metabolized by
3A4, 1A1, 2C8, 2J2
sGC stimulator should not be used in combination with
nitrates or PDE5 inhibitors
riociguat is contraindicated in ____________ and has to go through ___________
pregnancy
REMS
riociguat is approved for treatment in
PAH
chronic thromboembolic PH
if a woman with PAH becomes pregnant what should be discontinued?
endothelin receptor antagonists
riociguat
what is the best choice for treatment of a pregnant woman with PAH?
IV epoprostenol
pediatric PAH
treated similar to adults
bosentan only drug approved 3 and up
why should woman avoid getting pregnant if they have PAH?
changes in hemodynamics during pregnancy can lead to mortality
