Pharm: Pulmonary HTN

Question 1

What are the WHO functional classification classes for pulmonary HTN?

Answer 1

Class I: Have pulmonary HTN w/o limitation of activity

Class II: Have pulmonary HTN w/ slight limitation of activity, comfortable at rest

Class III: Have pulmonary HTN with marked limitation of activity, comfortable at rest

Class IV: Have pulmonary HTN with inability to carry out any activity without sx, manifest RHF, dyspnea or fatigue manifest at rest

Question 2

If a patient has a positive vasopressor test, what drug class has been proven to achieve sustained functional improvement and prolong survival?

Answer 2

+CBBs (nifedipine, diltiazem, or amlodipine)

Question 3

What are the classes of PAH medications?

Answer 3

• Prostacyclin analogs - made by endothelial cells
• Endothelin receptor antagonists - blocks ETA receptor alone or both ETA and ETB
• Phosphodiesterase 5 Inhibitors - induce relaxation and antiproliferative effects on vascular SM (slow breakdown of cGMP)
• Soluble guanylyl cyclase stimulants - mimic vasodilatory action of NO and potentiate NO release locally

Question 4

What drugs are in the prostanoid family?

Answer 4

Most contain “prost” in the word

Epoprostenol - IV only

Treprostinil - IV, oral, or inhaled

Iloprost - inhaled

Selexipag - Oral but expensive, better tolerated in kids

Question 5

What is the MOA of prostanoids?

Answer 5

• Binds GPCR on cell membrane to generate cAMP (mimics prostacyclins)
• Promote vascular relaxation
• Supress growth of SM cells
• Inhibit platelet aggregation

Question 6

What are some common adverse effects of prostanoids?

Answer 6

• All have AEs due to vasodilitory actions of medications (HA, flushing, jaw pain, edema, n/v)
• IV drugs (epoprostenol, treprostinil) have risk of sepsis due to chronic catheter use, treprostinil has pain at subQ infusion site
• Inhaled drugs have risk of cough & throat irritation
• Iloprost has serious AE of fainting due to hypotension, especially if SBP <85mmHG

Question 7

What are some considerations when choosing a prostanoind?

Answer 7

Route of administration:

• Epoprostenol: must be given IV with continuous infusion due to short 1/2 life, medication must be kept cold
• Treprostinil: given subQ infusion, QID inhalation, extended release oral form
• iloprost: inhalation
• Selexipag: Orally BID, consider in kids

Question 8

What are the endothelin antagonists?

Answer 8

Bosentan

Ambrisentan

Macitentan

Question 9

What is the MOA of endothelian antagonists?

Answer 9

• Blocks endothelian receptors that cause vasoconstriction and promote cell proliferation
• Can be selective for ETA (Ambrisentan) or non-selective for both ETA & ETB (Bosentan)

A for ETA only, B for Both

Question 10

What are some adverse effects common to endothelin antagonists?

Answer 10

• Teratogenesis (FDA category X)
  
  • Must use 2 forms of birth control!
• Anemia
• Reduced sperm count

Question 11

What are 2 serious side effect unique to bosentan?

Answer 11

• Hepatotoxicity (11%, potentially fatal)
• Accelerates metabolism of drugs such as warfarin but increases levels of drugs such as cyclosporine or glyburide

Question 12

What endothelian antagonist do you take once daily?

Answer 12

Macitentan

Question 13

What are the phosphodiesterase type V inhibitors?

Answer 13

sildenafil

tadalafil

riociguat

Question 14

What is the MOA of phosphodiesterase type V inhibitors and what is unique about the MOA of riociguat?

Answer 14

Blocks the breakdown of cGMP to potentiate cGMP mediated vascular SM relaxation

Riociguat has dual mode of action:

• sensitizes soluble guanylate cyclase to NO by stabilizing binding
• directly stimulates sGC independent of NO
• increases generation of cGMP

Question 15

What are some common adverse effects of PDE V inhibitors (not including riociguat)?

Answer 15

Generally well tolerated

HA, flushing, dyspepsia most common

Can cause visual disturbances and sudden hearing loss

Question 16

What are some drug interactions of PDE V inhibitors?

Answer 16

Large drops in BP when used with a-blockers for HTN or nitrates for anginal pain

Question 17

What are some adverse effects of riociguat?

Answer 17

• HA, hypotension, dizziness, dyspepsia most common
• Fetal harm: only available to women with negative pregnancy test, should avoid getting pregnant for 1 month after stopping med
• Do no give with NO donors or type V PDE inhibitors
• Many drug interactions

Question 18

What should you give tratement naive pts with WHO FC II?

Answer 18

If can tolerate combo therapy, give ambrisentan and tadalafil

If can’t tolerate combo therapy, start monotherapy with macitentan, ambisentan, riociguat, sildenafil or tadalafil

Question 19

What should you give for treatment naive pts with WHO FC III w/o evidence of rapid dz progression?

Answer 19

If can tolerate combo therapy, give ambrisentan and tadalafil

If can’t tolerate combo therapy, start monotherapy with macitentan, ambisentan, riociguat, sildenafil or tadalafil

Question 20

What should you give treatment naive pts with WHO FC III with evidence of rapid dz progression?

Answer 20

If able to manage parenteral prostanoids, give continuous IV epoprostenol, IV treprostinil, or SC treprostinil

If unable to manage, consider addition of inhaled or oral prostanoid

Question 21

What should you give pts with WHO FC IV?

Answer 21

If able to manage parenteral prostanoids, give continuous IV epoprostenol, IV treprostinil or SC treprostinil

If unable, give Iliprost(?spelling) + oral PDE-5 inhibitor + oral ET-antagonist

Question 22

What do you do in pts with inadequate response to initial therapy?

Answer 22

For WHO FC III or IV, add a second class

For WHO FC III or IV PAH patients who are deteriorating despite therapy with 2 classes, start a 3rd class

Question 23

What do you do in patients with inadequate response to maximal pharmacotherapy

Answer 23

Put them on transplant list if candidate for lung transplant

Incorporate palliative care services if not