Pharm: Pulmonary HTN Flashcards
What are the WHO functional classification classes for pulmonary HTN?
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
If a patient has a positive vasopressor test, what drug class has been proven to achieve sustained functional improvement and prolong survival?
+CBBs (nifedipine, diltiazem, or amlodipine)
What are the classes of PAH medications?
- 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
What drugs are in the prostanoid family?
Most contain “prost” in the word
Epoprostenol - IV only
Treprostinil - IV, oral, or inhaled
Iloprost - inhaled
Selexipag - Oral but expensive, better tolerated in kids
What is the MOA of prostanoids?
- Binds GPCR on cell membrane to generate cAMP (mimics prostacyclins)
- Promote vascular relaxation
- Supress growth of SM cells
- Inhibit platelet aggregation
What are some common adverse effects of prostanoids?
- 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
What are some considerations when choosing a prostanoind?
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
What are the endothelin antagonists?
Bosentan
Ambrisentan
Macitentan
What is the MOA of endothelian antagonists?
- 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
What are some adverse effects common to endothelin antagonists?
-
Teratogenesis (FDA category X)
- Must use 2 forms of birth control!
- Anemia
- Reduced sperm count
What are 2 serious side effect unique to bosentan?
- Hepatotoxicity (11%, potentially fatal)
- Accelerates metabolism of drugs such as warfarin but increases levels of drugs such as cyclosporine or glyburide
What endothelian antagonist do you take once daily?
Macitentan
What are the phosphodiesterase type V inhibitors?
sildenafil
tadalafil
riociguat
What is the MOA of phosphodiesterase type V inhibitors and what is unique about the MOA of riociguat?
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
What are some common adverse effects of PDE V inhibitors (not including riociguat)?
Generally well tolerated
HA, flushing, dyspepsia most common
Can cause visual disturbances and sudden hearing loss
What are some drug interactions of PDE V inhibitors?
Large drops in BP when used with a-blockers for HTN or nitrates for anginal pain
What are some adverse effects of riociguat?
- 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
What should you give tratement naive pts with WHO FC II?
If can tolerate combo therapy, give ambrisentan and tadalafil
If can’t tolerate combo therapy, start monotherapy with macitentan, ambisentan, riociguat, sildenafil or tadalafil
What should you give for treatment naive pts with WHO FC III w/o evidence of rapid dz progression?
If can tolerate combo therapy, give ambrisentan and tadalafil
If can’t tolerate combo therapy, start monotherapy with macitentan, ambisentan, riociguat, sildenafil or tadalafil
What should you give treatment naive pts with WHO FC III with evidence of rapid dz progression?
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
What should you give pts with WHO FC IV?
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
What do you do in pts with inadequate response to initial therapy?
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
What do you do in patients with inadequate response to maximal pharmacotherapy
Put them on transplant list if candidate for lung transplant
Incorporate palliative care services if not
