PHT

Question 1

What are the 4 drug categories for Pulm. Arterial Hypertension (PAH)

Answer 1

1. Prostanoids
2. PDE 5 inhibitors
3. Endothelin antagonists
4. Guanylate cyclase sensitizer

Question 2

What are the 4 Prostanoids

Answer 2

1. Epoprostenol
2. Treprostinil
3. Iloprost
4. Selexipag

Question 3

What is the suffix for the 2 PDE 5 inhibitors?

Answer 3

-afil

1. Sildenafil
2. Tadalafil

Question 4

What are the 3 Endothelin Antagonists and their suffix??

Answer 4

all end in -entan

1. Bosentan
2. Ambrisentan
3. Macicentan

Question 5

Name the 1 Guanylate cyclase sensitizer

Answer 5

Riociguat

Question 6

What was the first gene linked to PAH?

Answer 6

TGF-B receptor BMPR2, showed there is some family history with PAH

Question 7

WHO classifies PAH in class 1-4, how?

Answer 7

1. Pt has PAH but without resulting limitation
2. Pt has PAH with slight limitation of physical activity
3. Pt has PAH with marked limitation on physical activity
4. Pt has PAH with inability to carry out any physical activity

Question 8

What Test is recomended for those withclass 1 PAH?

Answer 8

Vasopressor Test

Question 9

Describe Vasopressor test

Answer 9

short-acting vasodilator is administered (epoprostenol, adenosine); test is + if Pulm artery pressure falls greater than 10mmhg; mean pulm. artery pressure is less than 40 or CO is unchanged or increased

Question 10

What 3 Tx are used for Pt with PAH that help but do NOT impact the PAH itself?

Answer 10

1. anticoagulants
2. Diuretics
3. Oxygen therapy

Question 11

Whats the MOA for PDE 5 inhibitor?

Answer 11

Induce relaxation and anti-proliferative effects on vascular smooth muscle cells

Question 12

What is the MOA for Guanylyl cyclase stimulants/

Answer 12

Directly mimic vasodilatory action of NO and potentiate effects of locally released NO

Question 13

Epoprostenol MOA/pharmacokinetics

Answer 13

Promotes vascular relaxation, binds to G-Protein coupled receptors on cell membrane to generate cAMP, has short 1/2 life.

Question 14

Epoprostenol toxicity/AE

Answer 14

Sepsis due to chronic catheter, headache (49%) and flushing(58%) most common AE

Question 15

Treprostinil MOA/Pharmaco

Answer 15

MOA same as others Subq infusion, longer 1/2-life than epo, qid inhalation form and extended-release oral form now available

Question 16

Treprostinil toxicity/AE

Answer 16

Most common is site pain at subQ injection (85%), headache

Question 17

Iloprost

Answer 17

Andminstered by inhalation 6-9 x/day. Fainting, cough, flushing

Question 18

Selexipag

Answer 18

Oral b.i.d, tablets are $225-$350 depending on dose so expensive

Question 19

Bosentan MOA

Answer 19

Endothelin antagonist blocks ET-a and ET-b endothelin receptors

Question 20

Bosentan toxicity/AE

Answer 20

Hepatotoxicity, drug interaction- must use 2 forms of birth control and limits oral controceptives

Question 21

Ambrisentan

Answer 21

Slectively blocks ET-a, doesnt damage liver, doesnt block oral contraceptives but use of 2 birth control still advised

Question 22

Macitentan

Answer 22

non-selective, main distinguisher is long half life of 18 hours. Cytochrome P450 effects similar to bosentan

Question 23

Sildenafil (viagra)

Answer 23

Selectively blocks PDE type V, oral, 1/2-life 4 hrs, may cause visual disturbances and mild hypotension

Question 24

Tadalafil (cialis)

Answer 24

Distinguished bc of long half life

Question 25

Riociguat

Answer 25

sensitizes soluable GC to endogenous NO and directly stimulates GC independent of NO; both lead to vasodilation, may cause fetal harm so preg. test