Drugs to Tx Pulmonary HTN

Question 1

Use of what drugs are viewed as a risk factor for pulmonary arterial HTN?

Answer 1

Fenfluramine/phentermine (“fen/phen” weight loss pills)

Question 2

What constitutes a positive vasopressor test?

Answer 2

1) Pulmonary artery pressure falls ≥ 10 mm Hg
2) Mean pulmonary artery pressure ≤ 40 mm Hg
3) Cardiac output is unchanged or increased

Question 3

If a patient’s vasopressor test is considered positive then what may they take to achieve sustained functional improvement and prolonged survival?

May they still take this drug if their vasopressor test was negative?

Answer 3

1) CCBs (nifedipine,
diltiazem or amlodipine)
2) No, they can be potentially deleterious in non-responders

Question 4

What drugs make up the prostanoids?

Answer 4

1) epoprostenol
2) treprostinil
3) iloprost
4) selexipag

(Prost)

Question 5

What do prostanoids mimic the actions of?

What does this cause?

Answer 5

Mimics the actions endogenous prostacyclins which causes:

1) Vascular relaxation
2) Suppression of vascular smooth muscle cell growth
3) Inhibition of platelet aggregation

Question 6

Prostanoids exert their effects by?

Answer 6

Binding to GPCRs to generate cAMP

Question 7

What clinical effects are seen with prostanoids in the treatment of PAH?

Answer 7

1) Lowers pulmonary arterial resistance
2) Decreases pulmonary arterial pressure
3) Increases exercise tolerance

Question 8

Which prostanoid has very short half-life (~ 6 min) and must be given by continuous IV infusion with a pump that can keep the drug cold?

Answer 8

epoprostenol

Question 9

Which prostanoid has multiple routes of administration such as subcutaneous infusion (but causes pain), qid inhalation, and extended-release oral form?

Answer 9

treprostinil

Question 10

How does treprostinil differ from epoprostenol when both are given by continuous IV infusion?

Answer 10

1) treprostinil has a longer half life (4 hours vs 6 min)

2) Doesn’t require refrigeration

Question 11

What serious adverse effects can be seen with both epoprostenol and treprostinil?

Answer 11

Sepsis due to chronic

catheter

Question 12

Which prostanoid is administered by inhalation 6-9 times per day?

Answer 12

iloprost

Question 13

What adverse effect is seen with iloprost?

Answer 13

Fainting due to hypotension

Question 14

Which prostanoid is administered orally BID?

Answer 14

selexipag

Question 15

What common side effects are seen with all prostanoids?

Answer 15

1) Headache
2) Flushing
3) Jaw pain

Question 16

What are the endothelin antagonists?

Answer 16

1) bosentan
2) ambrisentan
3) macitentan

(entan)

Question 17

Which endothelin antagonist nonspecifically blocks ETA and ETB endothelin receptors?

Answer 17

bosentan

Question 18

Which endothelin antagonist selectively blocks ETA endothelin receptors?

Answer 18

ambrisentan

Question 19

What clinical effects are seen with endothelin antagonists in the treatment of PAH?

Answer 19

Improves exercise tolerance and slows symptom progression

Question 20

How are the endothelin antagonists administered?

Answer 20

Orally

Question 21

What toxicities are noted with bosentan?

Answer 21

1) Hepatotoxicity

2) Teratogenesis

Question 22

What drug interaction does bosentan have causing acceleration of their metabolism?

Answer 22

1) Warfarin

2) Oral contraceptives

Question 23

How does ambrisentan differ from bosentan in terms of toxicities and drug interactions?

Answer 23

1) Does not damage liver

2) Does not accelerate metabolism of warfarin and oral contraceptives

Question 24

What toxicities are noted with ambrisentan?

Answer 24

Teratogenesis

Question 25

Which endothelin antagonist is a non-selective agent distinguished by ~18 hr half life that permits once/day dosing?

Answer 25

macitentan

Question 26

What are the Phosphodiesterase type V Inhibitors?

Answer 26

1) sildenafil
2) tadalafil

(afil)

Question 27

What is the MOA of the PDE type V inhibitors?

Answer 27

Potentiates cGMP mediated vascular relaxation

Question 28

What clinical effects are seen with PDE type V inhibitors in the treatment of PAH?

Answer 28

Improves exercise tolerance and slows symptom progression

Question 29

Which PDE type V inhibitors has the longer half life?

Answer 29

tadalafil

Question 30

The PDE type V inhibitors can cause a large drop in BP if taken with?

Answer 30

1) α-blockers for hypertension

2) Nitrates for anginal pain

Question 31

What is the guanylate cyclase sensitizer?

Answer 31

riociguat

Question 32

What is the MOA of riociguat?

Answer 32

Increased generation of cGMP

Question 33

What clinical effects are seen with riociguat in the treatment of PAH?

Answer 33

Improves exercise tolerance and slows symptom progression

Question 34

What should riociguat not be adminstered with?

Answer 34

1) Nitric oxide donors

2) PDE type V inhibitors

Question 35

What patients are classified as WHO Functional Class I?

WHO FC II?

WHO FC III?

WHO FC IV?

Answer 35

1) Pts with pulmonary HTN but without limitation of physical activity
2) Pts with pulmonary HTN which causes slight limitation of physical activity
3) Patients with pulmonary hypertension resulting in marked limitation of physical activity
4) Patients with pulmonary hypertension with inability to carry out any physical activity without symptoms

Question 36

In the Tx of naїve PAH patients with WHO FC II and WHO FC III (without rapid disease progression), what do you administer if they are able to tolerate combination therapy?

If they can’t, what are the monotherapy options given?

Answer 36

1) Ambrisentan and tadalafil

2) Either macitentan, ambrisentan, riociguat, sildenafil or tadalafil

Question 37

In the Tx of naїve PAH patients with WHO FC III (with rapid disease progression) and WHO FC IV what do you administer?

Answer 37

One of the parenteral prostanoids:

1) IV epoprostenol
2) IV treprostinil
3) SC treprostinil

Question 38

In the Tx of naїve PAH patients with WHO FC III (with rapid disease progression) and WHO FC IV what do you administer if they are unable to tolerate parenteral prostanoids?

Answer 38

1) Inhaled prostanoid
2) Oral PDE-5 inhibitor
3) Oral ET-antagonist

Question 39

What is the most common PAH drug combination?

Answer 39

Ambrisentan and tadalafil