Pulmonary Arterial HTN Flashcards
For PAH tx, ___________
there are medications specifically for tx of PAH
AMBITION trial
- 500 tx naive pts
- in combo group, AE were more common than in monotherapy groups
- rates of hypotension were similar
- rates of discontinuation and serious ADRs were similar across all groups
- thus, reasonable to combine tadalafil + ambrisentan as 1st line therapy
If pts do not improve to functional class I or II after CCB initiation…
start additional or alternative PAH therapy
When start intervening for PH?
Class II (slight limitation of physical activity - ordinary activity may cause symptoms. Comfortable at rest)
Prostacyclins reserved for WHO…
class III and IV pts
Adverse effects of ERA
- HA
- anemia
- UTI
- nasopharyngitis
- pharyngitis
- bronchitis
- peripheral edema
- increased LFTs (esp bosentan)
What is PAH?
progressive disease involving endothelial dysfunction –> elevated pulmonary arterial pressure and pulmonary vascular resistance
Therapeutic pathways for PAH: NO
- PDE5 inhibitors: sildenafil, tadalafil
- sGC: riociguat
Therapeutic pathways for PAH: Prostacyclin
- prostacyclins: epoprostenol (IV), iloprost (inh), treprostinil (IV, SQ, inh, oral)
- IP prostacyclin receptor agonist: selexipag
Therapeutic pathways for PAH: Endothelin
-Endothelin receptor antagonists = bosentan, macitentan, ambrisentan
riociguat cannot be used in combination with ____________
tadalafil or sildenafil due to risk of hypotension
How to diagnose PAH
- echocardiogram
- right heart catheterization (confirms diagnosis)
- exercise testing (distance walked in 6 minutes)
- biomarkers (BNP and NTproBNP)
What is riociguat?
soluble guanylate cyclase stimulator
alternative to PDE-5i
Guideline recommendation for WHO FC III:
WHO FC III w/ rapid progression or poor prognosis
- Candidate for parenteral prostanoids
2a. Yes –> SC treprostinil, IV treprostinil, IV epoprostenol
2b. No –> Consider inhaled or oral prostanoid (likely in combo w/ ERA + PDE-5i)
What is an acute vasoreactivity test (AVT)?
Acute response to pulmonary-specific vasodilators predicts response to CCBs
Prostacyclins are first line if
class IV or rapidly progressing class III
Agents during AVT include:
- inhaled NO
- IV epoprostenol
- IV adenosine
PAH is _____ and _____
fatal ; rare
PH is _____ than PAH
more common
When to consider CCBs in PAH pts that have undergone AVT?
In positive responders WITHOUT right-sided failure or other contra to CCB (do NOT use w/out positive AVT)
ADRs of prostacyclins
- HA
- jaw pain
- thrombocytopenia (more in epoprostenol)*
- hypotension*
Sildenafil/ERA drug interactions
- sildenafil increases bosentan
- bosentan decreases sildenafil
- mechanism: CYP 3A4 interaction
Most common prostacyclin medication errors
- flushing of the line (33%)
- calculation or concentration error (31%)
Effects of PAH
- pulmonary arterial wall and its smaller vessels become damaged, restricting blood flow to lungs
- left heart becomes smaller
- right heart becomes larger
- heart wall muscle becomes enlarged
Shorthand for pulmonary HTN
PH
for prostacyclins, do not use….
oral, inhaled and parenteral concurrently
PAH more prevalent in ________
women
Recommended CCBs in PAH pts that have undergone AVT
- long acting nifedipine
- long acting diltiazem*
- amlodipine*
NO VERAPAMIL due to negative inotropic effects
Causes of PAH
- unknown (idiopathic)
- genetics
- drug and toxin exposure
- disease associated w/ PAH: CHD, HIV, connective tissue disorders
Key information regarding PGI2 analogs
- prostacyclins require significant education
- $$$
- pts should have their own pumps and supplies
- interview pt, may need to call specialty pharmacy to confirm info
Pulmonary HTN is higher than normal BP ___________
IN THE LUNGS
not the same as HTN
PAH is considered group __ under WHO classification
1
Prostacyclins may be used in combo with
ERA plus PDE-5 or riociguat
Bosentan is the __________ but ambrisentan is __________. Bosentan must be ___________
original ; studied more ; monitored monthly
Prostacyclins available in
parenteral (IV, subQ), oral or inhaled formulations
What do prostacyclins so
- prostacyclins stimulate cAMP pathway to increase pulmonary vasodilation
- inhibits platelet aggregation
- parenteral prostacyclins = standard for severe PH with RV failure (subQ treprostinil is becoming most common)
Shorthand for pulmonary arterial HTN
PAH
Negative predictors of PAH
- advanced functional class
- poor exercise capacity
- high right atrial pressure
- right ventricular dysfunction
- low cardiac output
- underlying scleroderma
Endothelin Receptor Antagonists
- ET receptors on vascular smooth muscle mediate vasoconstriction
- blocking ET –> vasodilation
prostacyclins (oral) contraindicated with
strong CYP2C8 inhibitors (i.e. gemfibrozil)
PAH FC I pts ___________ require immediate drug therapy; consider CCB if responder
do not necessarily
Sildenafil (revatio) more so for __________
kids (20mg TID - might see 40 - 80 TID)
signs and symptoms of PAH
- fatigue
- fainting; light-headedness
- chest pain
- reported SOB
- reported palpitations
- edema
PDE inhibition
- decreases conversion of cGMP to GMP
- increased levels of cGMP –> pulmonary vasodilation
- can be monotherapy or combo, $$$
- often considered 1st line*
PAH prognosis
15% mortality in a year
Avoid using Endothelin Receptor Antagonists in
hepatically impaired pts
do not initiate if LFT > 3x ULN
Pharmacotherapy for PAH
- CCB
- iNO (inhaled NO)
- PDE-5 inhibitors
- Endothelin Receptor Antagonists (ERAs)
- Prostacyclins (oral, inhaled, parenteral)
- riociguat
All endothelin receptor antagonists are in
REMs program
prostacyclins (inhaled) [good for IV but don’t want to give IV i.e. can’t manage] examples
- iloprost (ventavis): requires up to 9 doses daily
- treprostinil (tyvaso): 1 ampule = 24 hrs of therapy
IV sildenafil
- rare, $$$
- restricted for pts who are strictly NPO
- dosing diff from oral
- must be given as slow infusion
must be in the __________ to use prostacyclins
hospital
Tyvaso more common due to ____________
- less frequent dosing
- new device can be charged
- assembling device is hard; done once every day
- txs throughout the day are 2 - 3 minutes
Guideline recommendation for WHO FC IV:
WHO FC IV
- Candidate for parenteral prostanoids
2a. Yes –> SC treprostinil, IV treprostinil, IV epoprostenol
2b. No –> Inhaled prostanoid + ERA + PDE-5i
Tadalafil (adcirca) more so for _________
adults (40mg QD)
Goals of PAH Tx therapy
- alleviate symptoms
- improve QOL
- prevent or delay disease progression
- reduce hospitalization
- improve survival
Guideline recommendation for AVT (acute vasoreactivity testing)
- Suggest acute vasoreactivity testing
2a. Positive responder –> Consider CCB (not for kids or infants)
2b. Negative responder, RV failure, or CCB contraindication –> Do not use CCB
PDE-5 Inhibitor ADRs
- flushing
- HA
- dyspepsia
- visual disturbances (blueish vision)
- tinnitus/hearing loss, sudden vision loss, hypotension*
