Pulmonary Arterial Hypertension

Question 1

What is PAH

Answer 1

High BP in pulmonary arteries from imbalance of vasoconstriction (↑TXA2, ↑endothelin1) & vasodilation (↓prostacyclin, ↓NO) → right ventricle HF Classified: Group 1 of Pulmonary Hypertension (PH) PAH = mPAP ≥ 25mmHg (Normal 8 -20)

Question 2

S/Sx of PAH

Answer 2

Fatigue

Dyspnea

Chest pain

Syncope

Edema

Tachycardia

Question 3

Non-pharm PAH tx

Answer 3

Sodium < 2.4g/day Vaccines: Flu, Pneumonia Avoid high altitudes O2 Sat > 90%

Question 4

PAH Tx Algorithm

Answer 4

Initial Drug Tx: warfarin INR goal: 1.5-2.5, loop diuretics & digoxin Perform: Right heart catheterization (gold standard) + Acute Vasoreactive Test (IV epoprostenol or IV adenosine or Inhaled NO) *Responder: mPAP ↓10 & < 40 → Tx: CCB: dilt-, amlo, nifed- (NOT verap-) *Non-Responder/failed CCB: ≥ 1 vasodilator: Prostacyclin, ERA, PDE5i or sGC

Question 5

Pulmonary Fibrosis

Answer 5

Scarred, damaged lung tissue. S/Sx: dyspnea, non-productive cough Causes: amiodarone, bleomycin, dronedarone, MTX Tx: DC offending drug, O2, pirfenidone (Esbriet), nintedanib (Ofeb): slows rate of decline in lung function. sildenafil (off-label

Question 6

Flolan

Answer 6

Epoprostenol

Question 7

Veletri

Answer 7

Epoprostenol

Question 8

Remodulin

Answer 8

Treprostinil

Question 9

Tyvaso

Answer 9

Treprostinil

Question 10

Orenitram

Answer 10

Treprostinil

Question 11

Ventavis

Answer 11

Iloprost

Question 12

Uptravi

Answer 12

Selexipag

Question 13

Prostacyclin Analogues ( Prostanoids)

Answer 13

Epoprostenol

Treprostinil

Iloprost

Selepaxig

Question 14

Key features of Prostacyclin Analogues

Answer 14

MOA: Potent vasodilator + inhibit platelet aggregation

Notes: parenteral: most potent

epoprostenol: protect from light

Flolan: req ice packs for solution

Question 15

Safety - Prostacyclin Analogues

Answer 15

ADR: Vasodilation reactions (Flushing), Jaw pain, Infusion-site pain Warning: Rebound PH (don’t ↓ dose or DC abruptly) Chronic IV infusions → Infections Avoid: Drugs that ↓prostaglandin (e.g., NSAIDs)

Question 16

Endothelin Receptor Antagonists

Answer 16

Bosentan

Ambrisentan

Macitentan

Question 17

Tracleer

Answer 17

Bosentan

Question 18

Letairis

Answer 18

Ambrisentan

Question 19

Opsumit

Answer 19

Macitentan

Question 20

Endothelin Receptor Antagonist - Key features

Answer 20

MOA: Blocks vasoconstriction & proliferation effects

bosentan: ↓ effectiveness of contraceptives

Question 21

Endothelin Receptor Antagonists - Safety

Answer 21

BBW: embryo-fetal toxicity (negative pregnancy test prior initiation; monthly thereafter),

bosentan: hepatotoxicity

C/I: pregnancy

ADR: HA, hepatotoxicity, ↓Hgb/Hct, fluid retention

**REMS** for all agents

Question 22

PDE-5 inhibitors

Answer 22

Sildenafil

Tadalafil

Question 23

Revatio

Answer 23

Sildenafil

Question 24

Adcirca

Answer 24

Tadalafil

Question 25

PDE-5 Inhibitor - Key features

Answer 25

MOA: PDE5i → ↑cGMP → pulmonary vasculature relaxation and vasodilation

Question 26

PDE-5 Inhibitor - Safety

Answer 26

C/I: Use w/nitrates or riociguat

Warning: hearing/vision loss, NAION (nonarteritic anterior ischemic optic neuropathy), priapism, hypotension ADR: HA

Question 27

Soluble Guanylate Cyclase Stimulator (sGC)

Answer 27

Riociguat

Question 28

Adempas

Answer 28

Riociguat

Question 29

Soluble Guanylate Cyclase Stimulator (sGC) - Key features

Answer 29

MOA: sensitizes sGC to endogenous NO and directly stimulates the receptor → ↑cGMP → relaxation and antiproliferative effects in pulmonary artery muscle cells

Question 30

Soluble Guanylate Cyclase Stimulator (sGC) - Safety

Answer 30

BBW: embryo-fetal toxicity (negative pregnancy test prior initiation; monthly thereafter)

C/I: Pregnancy, use w/nitrates or PDE5i

ADR: hypotension, HA
**REMS**