Pulmonary arterial hypertension Flashcards
what is pulmonary arterial hypertension
- progressive disease involving endothelial dysfunction -> elevated pulmonary arterial pressure and pulmonary vascular resistance
what is the mean pulmonary artery pressure (mPAP) in PAH
> 20 mmHg
what is pulmonary artery wedge pressure (PAWP) in PAH
<= 15 mmHg
what is the pulmonary vascular resistance (PVR) in PAH
> 2 Wood units
what is normal pulmonary arterial wedge pressure
4-12 mmHg
what is the gold standard way to diagnose PAH
right heart catheterization
what is another way other than right heart catheterization to evaluate PAH
echocardiogram
risk factors and associated conditions for PAH
- collagen vascular disease
- congenital heart disease
- portal htn
- HIV infection
- drugs and toxins
- pregnancy
main genetic factor for PAH
abnormal BMPR2 gene
what does PAH endothelial dysfunction cause
- decreased NO2 synthase, prostacyclin production
- increased thromboxane production, endothelin 1 production
what is PAH class 1
symptom free when physically active or resting
what is PAH class 2
- slight limitation of physical activity - ordinary activity may cause Sx
- comfortable at rest
what is PAH class 3
- marked limitation in physical activity - less than ordinary activity causes Sx
- comfortable at rest
what is PAH class 4
- significant Sx w/ activity
- Sx at rest
at what PAH class do we consider starting tx
class 2
PAH goals of therapy
- alleviate Sx
- improve QOL
- prevent or delay disease progression
- reduce hospitalization
- improve survival
what is the result of a positive acute vasoreactivity test (AVT)
drop in mPAP >10 mmHg w/ PAP less than 40 mmHg w/ stable-improved cardiac output
when should CCBs be considered for PAH
- positive responders to CCBs w/o right-sided failure or other CI to CCB
- do not use w/o positive AVT
why should verapamil not be used for PAH
due to negative inotropic effects
what to do if patient does not improve to functional class I or II after CCB initation
start additional or alternative PAH therapy
recommended PAH first line CCBs if patient is a positive responder
- long acting nifedipine 120-240 mg daily
- long acting diltiazem 240-720 mg daily
- amlodipine 20 mg daily
PDE-5i inhibition effects
- decreases conversion of cGMP to GMP
- increased levels of cGMP -> pulmonary vasodilation
PDE-5i meds for PAH
- sildenafil
- tadalfil
what do PDE-5i meds do that improves PAH
- improved 6MWD
- functional capacity
when are PDE-5i meds first line for PAH
functional class II and III w/o rapid progression
sildenafil (revatio) half life
5 hours
tadalafil (adcirca) half life
15-35 hours
sildenafil dose adjustments
none
tadalafil dose adjustments
renal
PDE-5i meds major drug interactions
- avoid use with riociguat or nitrates (hypotension)
- CYP3A4 substrates
PDE-5i drugs AEs
flushing, headache, dyspepsia, visual disturbances, priapism, tinnitus/hearing loss, sudden vision loss, hypotension
endothelin receptor antagonists moa
- ET receptors on vascular smooth muscle mediate vasoconstriction
- overexpression of ET-1 in PH patients, correlates with remodeling
- blocking ET -> vasodilation
when should endothelin receptor antagonists be used
an option in functional class II-IV
what is combo first line for class II and III without rapid progression
tadalafil + ambrisentan
what do endothelin receptor antagonists do
improve 6MWD, pro-BNP, delay time to clinical worsening, optimize hemodynamics
how soon are improvements expected with endothelin receptor antagonists
8-10 weeks
where are ETa receptors located
pulmonary smooth muscle walls
ETa receptors effects
promotes vasoconstriction, proliferation, inflammation
ETb receptors on endothelium effects
promote vasodilation, stimulate NO and prostacyclin production
ETb receptors on muscle cells of vascular walls effects
cause vasoconstriction and cell proliferation
what is going on with ET receptors in PAH
expression of ETb receptors are upregulated in the media of blood vessels (vasoconstriction)
soluble guanylate cyclase stimulator med
riociguat (adempas)
when could riociguat be used
may be used as an alternative to PDE-5i
why can’t riociguat be used with PDE-5i
risk of hypotension
prostacyclins moa
stimulates cAMP pathway to increase pulmonary vasodilation
what is standard tx for severe PH w/ RV failure
parenteral prostacyclins -> subQ treprostinil
when are prostacyclins used in PAH
reserved for class III and IV patients
what other drug classes may prostacyclins be used with
combination w/ ERA + PDE-5i or riociguat
treprostinil half life
4 hours
what should not be done w/ IV treprostinil
IV infusion requires stable access, do not co-infuse with anything else
when is IV used over subQ
for patients who cannot tolerate subQ
why is subQ treprostinil better than IV
- subQ avoids risk of central lines
- utilizes undiluted drug
common prostacyclin medication errors
- flushing of line
- calc or conc error
- programming error
- pump turned off
- inappropriate change in weight
when should lung transplantation be considered
for functional class III and IV patients w/ inadequate response to maximal pharmacotherapy
when are adjunct therapy considered
treat underlying/contributing conditions like htn/sleep apnea
when is anticoag adjunct therapy considered
- consider depending on cardiac function
- warfarin: INR goal 1.5-2.5
- aspirin 81 mg daily
when is diuretic adjunct therapy considered
to maintain euvolemia
other supportive therapies
- immunizations (influenza, pneumococcal, COVID, RSV)
- supplemental oxygen (pulmonary vasodilation)
- iron supplementation if deficient
- avoid air travel/high altitudes (may need supplemental O2 to keep saturations >91%)
why should pregnancy be avoided during PAH therapy
- estrogen containing contraceptives may increase VTE risk
- Bosentan can cause birth defects
- ERAs and riociguat are category X
