Pulmonary Arterial HTN

Question 1

For PAH tx, ___________

Answer 1

there are medications specifically for tx of PAH

Question 2

AMBITION trial

Answer 2

• 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

Question 3

If pts do not improve to functional class I or II after CCB initiation…

Answer 3

start additional or alternative PAH therapy

Question 4

When start intervening for PH?

Answer 4

Class II (slight limitation of physical activity - ordinary activity may cause symptoms. Comfortable at rest)

Question 5

Prostacyclins reserved for WHO…

Answer 5

class III and IV pts

Question 6

Adverse effects of ERA

Answer 6

• HA
• anemia
• UTI
• nasopharyngitis
• pharyngitis
• bronchitis
• peripheral edema
• increased LFTs (esp bosentan)

Question 7

What is PAH?

Answer 7

progressive disease involving endothelial dysfunction –> elevated pulmonary arterial pressure and pulmonary vascular resistance

Question 8

Therapeutic pathways for PAH: NO

Answer 8

• PDE5 inhibitors: sildenafil, tadalafil

- sGC: riociguat

Question 9

Therapeutic pathways for PAH: Prostacyclin

Answer 9

• prostacyclins: epoprostenol (IV), iloprost (inh), treprostinil (IV, SQ, inh, oral)
• IP prostacyclin receptor agonist: selexipag

Question 10

Therapeutic pathways for PAH: Endothelin

Answer 10

-Endothelin receptor antagonists = bosentan, macitentan, ambrisentan

Question 11

riociguat cannot be used in combination with ____________

Answer 11

tadalafil or sildenafil due to risk of hypotension

Question 12

How to diagnose PAH

Answer 12

• echocardiogram
• right heart catheterization (confirms diagnosis)
• exercise testing (distance walked in 6 minutes)
• biomarkers (BNP and NTproBNP)

Question 13

What is riociguat?

Answer 13

soluble guanylate cyclase stimulator

alternative to PDE-5i

Question 14

Guideline recommendation for WHO FC III:

WHO FC III w/ rapid progression or poor prognosis

Answer 14

1. 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)

Question 15

What is an acute vasoreactivity test (AVT)?

Answer 15

Acute response to pulmonary-specific vasodilators predicts response to CCBs

Question 16

Prostacyclins are first line if

Answer 16

class IV or rapidly progressing class III

Question 17

Agents during AVT include:

Answer 17

• inhaled NO
• IV epoprostenol
• IV adenosine

Question 18

PAH is _____ and _____

Answer 18

fatal ; rare

Question 19

PH is _____ than PAH

Answer 19

more common

Question 20

When to consider CCBs in PAH pts that have undergone AVT?

Answer 20

In positive responders WITHOUT right-sided failure or other contra to CCB (do NOT use w/out positive AVT)

Question 21

ADRs of prostacyclins

Answer 21

• HA
• jaw pain
• thrombocytopenia (more in epoprostenol)*
• hypotension*

Question 22

Sildenafil/ERA drug interactions

Answer 22

• sildenafil increases bosentan
• bosentan decreases sildenafil
• mechanism: CYP 3A4 interaction

Question 23

Most common prostacyclin medication errors

Answer 23

• flushing of the line (33%)

- calculation or concentration error (31%)

Question 24

Effects of PAH

Answer 24

• 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

Question 25

Shorthand for pulmonary HTN

Answer 25

PH

Question 26

for prostacyclins, do not use....

Answer 26

oral, inhaled and parenteral concurrently

Question 27

PAH more prevalent in ________

Answer 27

women

Question 28

Recommended CCBs in PAH pts that have undergone AVT

Answer 28

- long acting nifedipine - long acting diltiazem* - amlodipine* NO VERAPAMIL due to negative inotropic effects

Question 29

Causes of PAH

Answer 29

- unknown (idiopathic) - genetics - drug and toxin exposure - disease associated w/ PAH: CHD, HIV, connective tissue disorders

Question 30

Key information regarding PGI2 analogs

Answer 30

- prostacyclins require significant education - $$$ - pts should have their own pumps and supplies - interview pt, may need to call specialty pharmacy to confirm info

Question 31

Pulmonary HTN is higher than normal BP ___________

Answer 31

IN THE LUNGS not the same as HTN

Question 32

PAH is considered group __ under WHO classification

Answer 32

1

Question 33

Prostacyclins may be used in combo with

Answer 33

ERA plus PDE-5 or riociguat

Question 34

Bosentan is the __________ but ambrisentan is __________. Bosentan must be ___________

Answer 34

original ; studied more ; monitored monthly

Question 35

Prostacyclins available in

Answer 35

parenteral (IV, subQ), oral or inhaled formulations

Question 36

What do prostacyclins so

Answer 36

- 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)

Question 37

Shorthand for pulmonary arterial HTN

Answer 37

PAH

Question 38

Negative predictors of PAH

Answer 38

- advanced functional class - poor exercise capacity - high right atrial pressure - right ventricular dysfunction - low cardiac output - underlying scleroderma

Question 39

Endothelin Receptor Antagonists

Answer 39

- ET receptors on vascular smooth muscle mediate vasoconstriction - blocking ET --> vasodilation

Question 40

prostacyclins (oral) contraindicated with

Answer 40

strong CYP2C8 inhibitors (i.e. gemfibrozil)

Question 41

PAH FC I pts ___________ require immediate drug therapy; consider CCB if responder

Answer 41

do not necessarily

Question 42

Sildenafil (revatio) more so for __________

Answer 42

kids (20mg TID - might see 40 - 80 TID)

Question 43

signs and symptoms of PAH

Answer 43

- fatigue - fainting; light-headedness - chest pain - reported SOB - reported palpitations - edema

Question 44

PDE inhibition

Answer 44

- decreases conversion of cGMP to GMP - increased levels of cGMP --> pulmonary vasodilation - can be monotherapy or combo, $$$ - often considered 1st line*

Question 45

PAH prognosis

Answer 45

15% mortality in a year

Question 46

Avoid using Endothelin Receptor Antagonists in

Answer 46

hepatically impaired pts do not initiate if LFT > 3x ULN

Question 47

Pharmacotherapy for PAH

Answer 47

- CCB - iNO (inhaled NO) - PDE-5 inhibitors - Endothelin Receptor Antagonists (ERAs) - Prostacyclins (oral, inhaled, parenteral) - riociguat

Question 48

All endothelin receptor antagonists are in

Answer 48

REMs program

Question 49

prostacyclins (inhaled) [good for IV but don't want to give IV i.e. can't manage] examples

Answer 49

- iloprost (ventavis): requires up to 9 doses daily | - treprostinil (tyvaso): 1 ampule = 24 hrs of therapy

Question 50

IV sildenafil

Answer 50

- rare, $$$ - restricted for pts who are strictly NPO - dosing diff from oral - must be given as slow infusion

Question 51

must be in the __________ to use prostacyclins

Answer 51

hospital

Question 52

Tyvaso more common due to ____________

Answer 52

- less frequent dosing - new device can be charged - assembling device is hard; done once every day - txs throughout the day are 2 - 3 minutes

Question 53

Guideline recommendation for WHO FC IV: WHO FC IV

Answer 53

1. Candidate for parenteral prostanoids 2a. Yes --> SC treprostinil, IV treprostinil, IV epoprostenol 2b. No --> Inhaled prostanoid + ERA + PDE-5i

Question 54

Tadalafil (adcirca) more so for _________

Answer 54

adults (40mg QD)

Question 55

Goals of PAH Tx therapy

Answer 55

- alleviate symptoms - improve QOL - prevent or delay disease progression - reduce hospitalization - improve survival

Question 56

Guideline recommendation for AVT (acute vasoreactivity testing)

Answer 56

1. 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

Question 57

PDE-5 Inhibitor ADRs

Answer 57

- flushing - HA - dyspepsia - visual disturbances (blueish vision) - tinnitus/hearing loss*, sudden vision loss*, hypotension*