Drugs for Pulmonary HTN Flashcards
Drugs in prostanoid class
- epoprostenol
- treprostinil
- iloprost
- selexipag
MOA prostanoids
mimics endogenous prostacyclin to cause vascular relaxation, decrease growth of vascular smooth muscle, and inhibit platelet aggregation
describe epoprostenol
- prostanoid
- short 1/2 life (6 min)
- need to give in continuous IV that keeps the bag cold
- risk of sepsis due to indwelling catheter
describe treprostinil
- prostanoid
- given subcutaneously
- longer 1/2 life and no need for refrigeration (like epoprostenol)
describe iloprost
- prostanoid
- given by inhalation 6-9x per day
describe selexipag
- prostanoid
- given orally; BID
- EXPENSIVE $225- $350 each dose
What are the endothelin antagonists?
- Bosentan
- Ambrisentan
- Macitentan
describe Bosetan
- endothelin antagonist
- blocks ETa/ETb receptor
- improves exercise tolerance
side effects Bosetan
- hepatotoxicity
- teratogenesis
- BAD w/ oral contraceptive
- accelerates warfarin metabolism
describe Ambrisentan
- endothelin antagonist
- blocks ETa receptor
- teratogen
- no change in warfarin metabolism
- still need to use 2 forms of contraceptives
describe Macitentan
- endothelin antagonist
- non selective agent
- take 1x per day (long 1/2 life)
- teratogen
What is a concern for all endothelin receptor blockers
teratogenesis
MOA PDE 5 inhibitors
block conversion cGMP –> 5’ GMP to promote vascular relaxation
PDE5 inhibitors used for pulmonary HTN
- Sildenafil (viagra)
- Tadalafil (cialis)
benefits of using PDE5 inhibitors in pulmonary HTN
improve exercise tolerance and slow Sx progression
MOA guanylate cyclase sensitizer
sensitizes soluble guanylate cyclase (sGC) to endogenous nitric oxide by stabilizing NO-sGC binging
(increased cGMP means increased vasodilation)
describe Riociguat
- guanylate cyclase sensitizer
- may cause fetal harm
- may interact with drugs at CYP450
definition pulmonary HTN
MAP >25 mmHg at rest
Who is pulmonary HTN common in?
young mothers, but more common in females of any age
Pulmonary artery changes in PAH
1) vasoconstriction
2) inflammation
3) localized thrombus formation
4) obstructive remodeling of vessel wall
When are CCBs used
if vasopressor test is positive
what CCBs are used with positive vasopressor test
- nifedipine
- diltiazem
- amlodipine
describe vaspressor test
- short acting vasodilator administered
- test is positive if PAP falls more than 10 mmHg/MAP is less than 40 mmHG
- give CCBs in addition if positive
Symptoms pulmonary HTN
- dyspnea on exertion
- syncope
- swelling in legs/ankles
- cyanotic lips/skin
Risk factors pulmonary HTN
- family history
- BMPR2 gene
- HIV infection
- portal HTN
- fen/phen use
Symptomatic profile of WHO functional class I of pulmonary HTN
patients with pulmonary HTN but without resulting limitation of physical activity
Symptomatic profile of WHO functional class II of pulmonary HTN
patients with pulmonary HTN resulting in slight limitation of physical activity. Comfortable at rest. Ordinary physical activity causes dyspnea/fatigue
Symptomatic profile of WHO functional class III of pulmonary HTN
patients with pulmonary HTN resulting in marked limitation of physical activity. Comfortable at rest. Less than ordinary physical activity causes dyspnea/fatigue
Symptomatic profile of WHO functional class IV of pulmonary HTN
Patients with pulmonary HTN with inability to carry out any physical activity without symptoms. Manifest signs of right heart failure
Which class of drugs has caused sudden hearing loss and/or visual disturbances (e.g., lack of color discrimination) when used by some patients?
PDE 5 inhibitors
What drug combo is typically used for patients with WHO FC II pulmonary HTN?
ambrisentan and tadalafil
At what point are prostanoids indicated for treatment-naive patients requiring therapy for pulmonary hypertension?
WHO FC III, evidence of rapid disease progression
