Pulm: Drugs to Treat Pulmonary HTN

Question 1

WHO Class I-IV of Pulmonary HTN:

Answer 1

I: pHTN w/o limitations
II: pHTN w slight limitation
III: pHTN w marked limitation
IV: pHTN w inability to carry out any physical activity

Question 2

When would you use dihydropyridine CCBs for pHTN?

Answer 2

If they have a positive vasopressor test

-if negative, they may have adverse effects

Question 3

What three treatments are used in pHTN that have very little impact on the hypertension itself?

Answer 3

Anticoagulants-to prevent thrombi
Diuretics-for R HF
Oxygen

Question 4

MOA of prostanoids (contain PROST)?

Answer 4

Mimics the actions of prostacyclin, binds Gs=increase cAMP

• vascular relaxation
• suppresses growth of smooth muscle
• inhibits platelet aggregation

Question 5

Effects of prostinoids on pHTN?

Answer 5

Lowers pulmonary artery resistance and pressure, increases exercise tolerance, and improves short term survival

Question 6

Adverse effects of Prostinoids?

Answer 6

If given IV (epoprostenol and treprostinil):
Sepsis through catheter, life treatening if pump is clogged

Others: nausea, headache, flushing

Question 7

Which prostanoid is given subQ?

Answer 7

Treprostinil

-painful!

Question 8

What is special about treprostinil’s ROA?

Answer 8

Longer half life and no refrigeration

Lots of Routes!
-SubQ, QID Inhalation, and extended release oral form available

Question 9

Which drugs are the prostinoids?

Answer 9

EpoPROSTenol, TrePROSTinil, iloPROST, Selexipag

Question 10

Which prostinoid is only inhaled?

Answer 10

Iloprost

Question 11

Which prostinoid is administered orally, BID?

Answer 11

Selexipag

-very expensive

Question 12

What are the two endothelin antagonists?

Answer 12

Bosentan and Ambrisentan

-sentan!

Question 13

Which endothelin antagonist is nonspecific at the ETa and ETb receptors? Which one is specific?

Answer 13

Bosentan is nonspecific, while ambrisentan is specific

Question 14

Effects of the endothelin antagonists?

Answer 14

Reduce the amount of vasoconstriction and improves exercise intolerance in pHTN

Question 15

Which of the endothelin antagonists interacts with warfarin and oral contraceptives?

Answer 15

Bosentan

-accelerates metabolism of both warfarin and oral contraceptives

Question 16

Which of the endothelin antagnists is teratogenic? What about hepatotoxic?

Answer 16

Teratogenic=Bosentan and Ambrisentan

Hepatotoxic=Bosentan only

Question 17

which drugs are PDE-5 antagonists?

Answer 17

Sildenafil and tadalafil

Question 18

What are the effects of the PDE-5 antagonists?

Answer 18

Prevent breakdown of cGMP, so relax smooth muscle

-Improve exercise intolerance and slow symptoms in pHTN

Question 19

Which PDE-5 antagonists has a longer half life, Sildenafil or tadalafil?

Answer 19

Tadalafil

Question 20

MOA of Riociguat? (3)

Answer 20

Sensitizes soluble guanylate cyclase (sGC) to NO
-stabilizes the binding

Directly stimulates sGC

Increases generation of cGMP=vasodilation

Question 21

Adverse effects of Riociguat?

Answer 21

Hypotension, headache, dizziness, and dyspepsia

-possible severe bleeds and fetal harm

Question 22

Should you take riociguat while pregnant?

Answer 22

Nope

Question 23

Tx for pt with class II or III pHTN and no disease progression, who is willing to take combined therapy?

Answer 23

Ambrisentan and tadalafil

Question 24

Tx for pt with class II and III pHTN, with NO disease progression and wants monotherapy?

Answer 24

Endothelin Antag: Macitentan, ambisentan

Guanylate Cyclase sensitizer: riociguat

PDE-5 blockers: sildenafil, tadalafil

Question 25

If pt has class III pHTN w disease progression or class IV pHTN, what should you use to treat?

Answer 25

A Prostinoid

• IV Epoprostenol
• IV or SubQ Treoprostinil

Question 26

If pt has class IV pHTN and is not willing to take do IV prostanoids, what should you give?

Answer 26

Inhaled prostanoid+oral PDE-5 (-fil) and oral ET-antagonist

Question 27

If a pt with class IV pHTN is treated with a a prostinoid and is still unresponsive, what should you do?

Answer 27

Add a second or even third class!

-after that, list for lung transplant

Question 28

most common combo of drugs used to treat pHTN?

Answer 28

Tadalafil + ambrisentan