(6.1) Pulmonary Hypertension (Wolff)

Question 1

What are the (4) prostanoids?

Answer 1

-prost

Epoprostenol

Treprostinil

Iloprost

Selexipag

Question 2

What are the (2) PDE 5 inhibitors?

Answer 2

-afil

Sildenafil

Tadalafil

Question 3

What are the (3) endothelin antagonists?

Answer 3

-sentan

Bosentan

Ambrisentan

Macicentan

Question 4

What is the (1) guanylate cyclase sensitizer?

Answer 4

Riociguat

Question 5

If you get a positive CCB vasopressor test…

What drugs do you use?

Answer 5

Nifedipine

Diltiazem

Amlodipine

Question 6

What is the primary target for the drugs we are learning for this lecture?

Answer 6

Pulmonary aterial hypertension (PAH)

Question 7

What is the definition of PAH?

Answer 7

Sustained elevation of mean pulmonary arterial pressure (mPAP) is

greater than or equal to 25mmHg at rest

Question 8

What is the normal pulmonary pressure?

Answer 8

14 plus or minus 3 mmHg

Question 9

What population is typically affected by pulmonary HTN?

Answer 9

Young women

Question 10

What is pulmonary arterial hypertension (PAH) characterized by?

Answer 10

Progressive increase in pulmonary vascular resistance (PVR)

Question 11

What does PAH eventually lead to (anatomically)?

Answer 11

Right ventricular overload –> right ventricular failure = premature death

Question 12

What are the EARLY symptoms of PAH?

Answer 12

Dyspnea upon exertion

Fatigue

Chest pain

Tachycardia

Pain on the upper right side of the abdomen

Anorexia

Question 13

What are the LATE symptoms of PAH?

Answer 13

Syncope

Swelling in legs and ankles

Cyanotic lips and skin

Question 14

What is a MAJOR genetic correlation to produce PAH?

Answer 14

BMPR2

Question 15

What is a MAJOR drug that can predispose pts to PAH?

Answer 15

Fenfluramine/phentermine

“fen/phen” weight loss pill

Question 16

What are key components (ligands) involved in pulmonary vascular remodeling?

Answer 16

5-HT

ET-1

Question 17

What is the gold standard for measuring pulmonary pressure?

Answer 17

Right heart catheterization

Question 18

What is the MOA for epoprostenol?

Answer 18

Mimics the actions of endogenous prostacyclin

(endogenous prostacyclin is a compound that promotes vascular relaxation)

Question 19

Noteworthy about epoprostenol?

Answer 19

VERY SHORT HALF LIFE!!!

(6 min)

Must be given by continuous IV

Question 20

What are the toxicities associated with epoprostenol?

Answer 20

Sepsis due to chronic catheter

Life threatening problems if pump lines become clogged

Common side effects = N/V, Headace, flushing jaw pain

Question 21

Since epoprostenol wasn’t great…came out with another drug that has the same MOA, but has a few differences in the pharmacokinetics…

What drugs am I talking about?

Answer 21

Treprostinil

Question 22

What is unique about the pharmacokinetics of treprostinil?

Answer 22

SubQ infusion with a LOT of pain

Higher half life (4hrs) than epoprostenol

Doesn’t require refrigeration

Question 23

Same MOA as both epoprestenol and treprostinil… slightly different pharmacokinetics and toxicities…

What drug am I talking about?

Answer 23

Iloprost

Question 24

What are the unique pharmacokinetics of iloprost?

Answer 24

Administered via INHALATION

Question 25

What are the side effects of **Iloprost?**

Answer 25

**Fainting** due to hypotension Cough, headache, flushing, **jaw pain**

Question 26

Since epoprostenol, treprostinil, iloprost all had some bad qualities to them, came out with another drug that is an **oral medication** used to treat PAH. What drug am I talking about?

Answer 26

Selexipag

Question 27

What is the major downside to using **selexipag?**

Answer 27

SUPER EXPENSIVE $225 per pill

Question 28

What is the MOA of **bosentan?**

Answer 28

Nonspecifically blocks the ET_A and ET_B endothelin receptors

Question 29

What are the side effects associated with **bosentan?**

Answer 29

Hepatotoxicity Teratogenesis

Question 30

What are the noteable drug interactions with **bosentan?**

Answer 30

ORAL CONTRACEPTIVES Warfarin

Question 31

What is the MOA of **ambrisentan?**

Answer 31

SELECTIVELY blocks the **ET_A receptors**

Question 32

What are the advantages and disadvantages of using **ambrisentan?**

Answer 32

Disadvantage: SUPER expensive, teratogenesis Advantages: Does not damage liver, does not interfer with warfarin or oral contraceptives

Question 33

MOA of **sildenafil?**

Answer 33

Selectively blocks phosphodiesterase type V

Question 34

What is the MOA of **riociguat?**

Answer 34

Dual mode of action: 1) Sensitizes soluble guanylate cyclase (sGC) to endogenous nitric oxide (NO) 2) Directly stimulates sGC independent of NO (Together, the increased generation of cGMP leads to increased vasodilation)