PAH
P A H PULMONARY
ARTERIAL
HYPERTENSION
An elevated mean pulmonary arterial pressure
(mPAP) >20mmHg, confirmed by RIGHT HEART
CATHETERIZATION
PAH is the specific category of PH
without association with LV, lung
disease and thrombosis
PAH CAN BE...
PAH CAN BE...
idiopathic
inherited
drug or toxin induced
secondary to a primary infection
or disease
persistent PH of newborn
Drugs associated with PAH
Aminorex
Benfluorex
Dasatinib
Dexfenfluramine
Fenfluramine
Methamphetamines
Toxic rapeseed oil
Appetite suppstressants,
amphetamines and SSRIs
increase serotonin levels
Serotonin acts as a
growth factor for
pulmonary arterial
smooth muscle cells
Hyperproliferation of PA
leads to hypertension
FUNCTION AL CLASS WHO-FC
FUNCTION AL CLASS WHO-FC
ival
n Surv
Media
5
Years:
CL ASS I
ation of
No limit
l activity
physica
I
SS I
f
A
L
C
on o
i
t
a
t
y
limi
t
h
tivit
g
c
a
Sli
l
sica
phy
Me
Media
n Surv
ival Ye
ars: 0.
5
CL AS
S III
More
limita
ti
phys
ical a on of
ctivit
y
CL ASS IV
Uncomfortab
le at
dian Su
rest
rvival Y
ears: 2
R
ig
ht heart failu
.5
re
ENDOTHELIN INHIBITOR
NITRIC OXIDE
PROSTACYCLIN
Dual ERAs
blocks ET-1 binding to
both ET A&B receptors,
inhibit vasoconstriction
and proliferation
Bosentan
Macitentan
Selective ERAs
blocks ET A only,
retaining the ET B effect
of vasodilation and antiproliferation
Ambrisentan
CI: PREGNANCY, LIVER
IMPAIRMENT
PDE5 inhibitors
block degradation of
NO, promotes
vasodilation and antiproliferation
Sildenafil
Tadalafil
sGC stimulator
downstream of NO
pathway, activate
sGC, increase cGMP
Riociguat
IP receptor agonists(IV)
bind to prostacyclin
receptor and activate
cAMP, leading to
vasodilation, antiproliferation and antiplatelet.
Epoprostenol
Treprostinil
Selexipag(new oral)
CI: HYPOTENSION, NO
DONORS, OCULAR
DISEASE, PREGNANCY
If not vasoreactive, FC I-II, START
WITH dual oral or mono therapy
For advanced disease, need triple
therapy with at least one of IV IP
agonists
Triple Tx with Selexipag showed no
difference compared to dual oral
Tx in RCT
Adherence issues: Tadalafil daily vs
Sildenafil TID
For IV drugs, need continuous
infusion and will carry pumps
around
ADRs: vasodilation: flushing,
headache, edema, congestion
TX CHO ICE
TX CHO ICE
DI with anticoagulants.
monitor for bleeding
Special ADR: Jaw pain
VASORE ACTIVIT Y
VASORE ACTIVIT Y
Test for mPAP reduction by at least
10mmHg after administration of a
short-acting vasodilator and less than
40mmHg, with minimal change on
systemic blood pressure
If positive, which means PA is sensitive
and reactive to vasodilation
START CCB before advanced therapy
above
Amlodipine, Nifedipine, Diltiazem
Reference
Lecture notes by Nilu Partovi(PharmD), Dynamed-Pulmonary Arterial Hypertension, Lexicomp,Chin, K. M., Sitbon, O., Doelberg,
M., Feldman, J., Gibbs, J. S. R., Grünig, E., Hoeper, M. M., Martin, N., Mathai, S. C., McLaughlin, V. V., Perchenet, L., Poch, D.,
Saggar, R., Simonneau, G., & Galiè, N. (2021). Three- Versus Two-Drug Therapy for Patients With Newly Diagnosed Pulmonary
Arterial Hypertension. Journal of the American College of Cardiology, 78(14), 1393–1403.
https://doi.org/10.1016/j.jacc.2021.07.057
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