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Flashcards in PHARM: PAH Deck (39):
1

True or False: most drugs used against systemic HTN work for pulmonary HTN.

FALSE: only CCBs have been shown to help pulmonary as well as systemic HTN

2

What are the 4 main "causes" of PAH?

1) Impalance between vasoconstriction and vasodilation
2) SM/Endothelial cell proliferation, propogation, and hypertrophy
3) Thrombosis
4) Fibrosis

3

What is the "sine qua non" of patient with IPAH or heritable PAH?

plexiform lesions (thickened arteroiles as a result of sheer stress)

4

What does prostacyclin do in pulmonary arteries?

inhibits platelet activation and smooth muscle growth
(also vasodilates)

5

What does NO do in pulmonary arteries?

increases cGMP which leads to inhibition of platelet activation and smooth muscle activity (so vasodilation)

6

What does TXA2 do in pulmonary capillaries?

activates platelets

7

What does endothelin-1 do in pulmonary vessels?

induces smooth muscle growth

8

What are the 4 classes of drugs used to treat PAH?

Prostanoids
Endothelin-1 Receptor Antagonists
Phosphodiesterase Type 5 Inhibitors
CCBs

9

What is a prostanoid?

prostacyclin derivative that induces pulmonary artery vasodilation, retards smooth muscle growth and disrupts platelet aggregation

10

List the prostanoids used to treat PAH.

Epoprostenol
Iloprost
Treprostinil

11

What are the disadvantages of prostanoids?

Very expensive and NONE of them are oral (Epoprostenol is IV, Iloprost is inhaled, Treprostinil is SC or IV)

12

Why does epoprostenol have to be IV infused?

it has a 3-5 minute half-life (very short)

13

What are the dose limiting toxicities of epoprostenol?

Hypotension
Muscle pains
HA
Flushing

14

What are the AEs of iloprost?

Cough
Flushing
Hemoptysis* (rarely)

15

What are the AEs of treprostinil?

Injection site erythema, rash, pain.
Jaw pain
CYP2C8 drug interactions

16

What is the MOA of endothelin-1 receptor antagonists?

block the smooth muscle proliferaiton and pulmonary arterial vasoconstriction produced by endothelin-1 upon binding to its Type A (smooth muscle) and Type B (endothelial cell) receptors

17

What is the advantage of endothelin-1 receptor antagonists over prostacyclins?

they are all orally active!

18

What are the disadvantages of endothelin-1 receptor antagonists?

Expensive
TERATOGENIC

19

What are the 2 endothelin-1 receptor antagonists used to treat PAH?

Bosentan
Ambrisentan

20

What are the AEs of Bosentan?

Liver and Blood toxicities
CYP interactions

21

What are the AEs of Ambrisentan?

Peripheral Edema
HA

*Less likely to cause liver problems and have CYP interactions

22

What is the MOA of phosphodiesterase Type 5 inhibitors?

perpetuate endogenously generated cGMP leading to vasodilation and reduce cellular proliferation

23

Who should NEVER talk a phosphodiesterase Type 5 inhibitor?

someone taking organic nitrates

24

List the 2 phosphodiesterase Type 5 inhibitors used to treat PAH.

Sildenafil
Tadalafil

25

What are phosphodiesterase Type 5 inhibitors also used for?

erectile dysfunction
benign prostatic hyperplasia

26

What are some AEs of Sildenafil?

HA
Epistaxis
Dizziness with sudden hearing loss
CYP interactions

27

What are some AEs of tadalafil?

headache
back pain
change in color vision (NAION)
CYP interactions

28

What is the MOA of CCBs?

prevent access of Ca2+ into cells during membrane depolarization (block the key mediator of SM contraction, permitting a vasodilation to endure)

29

True or false: all patients with PAH respond well to CCBs.

FALSE: some can even get worse

30

How do you test to see if patient will respond to CCBs?

"vasodilator challenge"

31

What is involved with a vasodilator challenge?

IV epoprostenol,IV adenosine, or inhaled NO are received at escalated dosing rates while PAP and CO are monitored for 2-3 hours

32

What is considered to be a positive vasodilator challenge?

Decreased pulmonary arterial pressure with NO decrease in CO

33

What CCBs have been used to treat PAH?

Diltiazem (immediate release)
Nifedipine (extended release)
Amlodipine

34

What are the AEs of diltiazem?

bradycardia
hypotnesion
HA
edema
cyp interactions

35

What are the AEs of nifedipine?

Flushing
edema
hypotension
heartburn
cyp interactions

36

What are the AEs of amlodipine?

edema
fatigue
hypotension
cyp interactions

37

Why is verapamil NOT used in PAH treatment?

it has strongly negative inotrophic properties which make it more likely to cause bradycardia

38

What percent of tested patients are positive for the vasodilator challenge?

15%

39

What is the goal of CCB therapy for PAH patients?

to reach NYHA-FC 1 or II after 3-4 months: meaning mild symptoms and/or slight limitation during normal physical activity or less