Pharm - Pulmonary HTN

Question 1

First Gene Linked to PAH, but is seen in less than <25% of idiopathic.

Answer 1

BMPR2

Question 2

Weight Loss pills associated with PAH

Answer 2

“Fen/Phen”

Fenfluramine/Phenteramine

Question 3

Who is the Vasopressor test indicated for?

Answer 3

Group I PAH Pt’s

Question 4

How does the Vasopressor Test work?

Answer 4

A Short-Acting Vasodilator is administered (adenosine, inhaled NO, epoprostenol)

Test is Positive if:

• Pulmonary arterial pressure falls >10mmHg
• Mean Pulmonary Arterial pressure <40mmHg
• Cardiac output is unchanged or increased

Question 5

What percent of Pt’s have a positive response to the Vasopressor Test? Which PAH Pt’s are more likely to respond? Which are less likely to respond?

Answer 5

13%

Pt’s with idiopathic, familial, or Anorexigenic-Induced PAH are more likely to respond

Pt’s with PAH caused by Connective Tissue Dz, HIV, Toxins are less likely to respond

Question 6

What percent of the 13% of Vasopressor Test Responders will achieve sustained functional improvement and prolonged survival with CCB’s (Dihydropyridines or Diltiazem)?

Answer 6

50% (1/2) of Vasopressor Test Responders will achieved sustained functional improvement and prolonged survival with CCB’s (Dihydropyridines and Diltiazem)

Question 7

What effect might CCB’s (Dihydropyridines and Diltiazem) have in Vasopressor test non-responders?

Answer 7

CCB’s may potentially be deleterious in Vasopressor Non-responders

Question 8

What are the 4 Prostanoids (Prostacyclin-Analogs) we discussed?

Answer 8

Epoprostenol
Trepostinil
Iloprost
Selexipag

Question 9

Which Prostanoid used to treat PAH must be administered by continuous IV infusion with a pump that keeps the drug cool, as it has a very short half-life of 6min? This was the first discovered of the Prostanoids.

Answer 9

Epoprostenol

Question 10

What are the adverse effects of Epoprostenol?

Answer 10

Sepsis due to Chronic Catheter

Life-Threatening problems if the required pump (to keep the drug cool) becomes clogged.

Common side effects include N/V, HA, Flushing, Jaw Pain

Question 11

Which Prostanoid used to treat PAH was initially approved for continuous Subcutaneous infusion, however resulted in intense pain, and thus now is diluted and administered via continuous IV infusion with a pump? It has a half-life of 4 hours and does NOT require Refrigeration, aid inhalation form is also now available.

Answer 11

Trepostinil

Question 12

What are the adverse effects of the Prostanoid, Treprostinil?

Answer 12

Sepsis due to chronic catheter

Common Side effects include site pain with subcutaneous infusion, Jaw Pain, Diarrhea, Edema, and Nausea.

If inhaled - Cough, HA, Throat irritation, Nausea, flushing, dizziness

Question 13

Which Prostanoid, used to treat PAH, is administered by Inhalation 6-9 times a day?

Answer 13

Iloprost

Question 14

What are the adverse effects of the Prostanoid, Iloprost?

Answer 14

Fainting due to hypotension, especially if SBP is <85mmHg

Common Side effects including Cough, HA, Flushing, Jaw Pain

Question 15

Which Prostanoid, used to treat PAH, is administered orally bid, with tablets costing $225 each or $350 each for higher doses?

Answer 15

Selexipag

Question 16

What are the adverse effects of Selexipag?

Answer 16

HA, Flushing, Diarrhea, N/V, Jaw/Limb/Muscle Pain, Skin rash

Question 17

What are 3 Endothelin-1 Receptor Antagonists we discussed?

Answer 17

Bosentan
Ambrisentan
Macitentan

Question 18

Endothelin-1 Receptor Antagonist which nonspecifically blocks ETa and ETb Endothelin Receptors, and only have has 50% bioavailability in presence or absence of food?

Answer 18

Bosentan

Question 19

What are some of the adverse effects of Bosentan?

Answer 19

Potentially Fatal hepatotoxicity
Teratogenesis
HA, Flushing, Peripheral Edema, Nasal Congestion, Anemia, and Reduced Sperm Production

Question 20

What are the significant Drug Interactions of Bosentan?

Answer 20

Accelerates metabolism of Warfarin and Oral Contraceptives (must use more than 1)

Increases concentration of other drugs including cyclosporine or glyburide

Question 21

Endothelin-1 Receptor Antagonist Which selectively blocks ETA receptors that cause vasoconstriction and promote cellular proliferation?

Answer 21

Ambrisentan

Question 22

What are some of the adverse effects of Ambrisentan?

Answer 22

Teratogenesis

Peripheral Edema, Nasal Congestion, Anemia, and Reduced Sperm Production

Question 23

What are the significant Drug Interactions of Ambrisentan?

Answer 23

Does NOT accelerate metabolism of Warfarin or Oral Contraceptives, BUT must still use 2 forms of Birth Control

Question 24

Endothelin-1 Receptor Antagonist that is a Non-Selective Antagonist, distinguished by an approximately 18hr half-life that permits Once a day dosing. It accelerates the metabolism of Warfarin and Oral Contraceptives similar to Bosentan?

Answer 24

Macitentan

Question 25

What PDE-5 Inhibitors may be used to treat PAH?

Answer 25

Sildenafil (Viagra)

Tadalafil (Cialis)

Question 26

What Guanylate Cyclase Sensitizer may be used in the treatment of PAH?

Answer 26

Riociguat

Question 27

What is the MOA of Riociguat?

Answer 27

Riociguat sensitized soluble Guanylate Cyclase to Endogenous Nitric Oxide (NO) by stabilizing the binding of sGC to NO. It also directly stimulates sGC independent of NO. It leads to increased generation of cGMP -> Increased vasodilation

Question 28

Which medication for PAH may be used to treat Type 4 PAH on its own?

Answer 28

Riociguat

Question 29

What are the adverse effects of Riociguat?

Answer 29

Hypotension, HA, Dizziness, and Dyspepsia

rarely severe bleeding may be seen

May cause fetal Harm - only available to women with a negative pregnancy test, and should avoid pregnancy for 1 month following stopping

Question 30

What are some of the drug interactions of Riociguat?

Answer 30

Should not be administered with NO donors or PDE-5 Inhibitors