Drugs to Tx Pulmonary HTN Flashcards
Use of what drugs are viewed as a risk factor for pulmonary arterial HTN?
Fenfluramine/phentermine (“fen/phen” weight loss pills)
What constitutes a positive vasopressor test?
1) Pulmonary artery pressure falls ≥ 10 mm Hg
2) Mean pulmonary artery pressure ≤ 40 mm Hg
3) Cardiac output is unchanged or increased
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?
1) CCBs (nifedipine,
diltiazem or amlodipine)
2) No, they can be potentially deleterious in non-responders
What drugs make up the prostanoids?
1) epoprostenol
2) treprostinil
3) iloprost
4) selexipag
(Prost)
What do prostanoids mimic the actions of?
What does this cause?
Mimics the actions endogenous prostacyclins which causes:
1) Vascular relaxation
2) Suppression of vascular smooth muscle cell growth
3) Inhibition of platelet aggregation
Prostanoids exert their effects by?
Binding to GPCRs to generate cAMP
What clinical effects are seen with prostanoids in the treatment of PAH?
1) Lowers pulmonary arterial resistance
2) Decreases pulmonary arterial pressure
3) Increases exercise tolerance
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?
epoprostenol
Which prostanoid has multiple routes of administration such as subcutaneous infusion (but causes pain), qid inhalation, and extended-release oral form?
treprostinil
How does treprostinil differ from epoprostenol when both are given by continuous IV infusion?
1) treprostinil has a longer half life (4 hours vs 6 min)
2) Doesn’t require refrigeration
What serious adverse effects can be seen with both epoprostenol and treprostinil?
Sepsis due to chronic
catheter
Which prostanoid is administered by inhalation 6-9 times per day?
iloprost
What adverse effect is seen with iloprost?
Fainting due to hypotension
Which prostanoid is administered orally BID?
selexipag
What common side effects are seen with all prostanoids?
1) Headache
2) Flushing
3) Jaw pain
What are the endothelin antagonists?
1) bosentan
2) ambrisentan
3) macitentan
(entan)
Which endothelin antagonist nonspecifically blocks ETA and ETB endothelin receptors?
bosentan
Which endothelin antagonist selectively blocks ETA endothelin receptors?
ambrisentan
What clinical effects are seen with endothelin antagonists in the treatment of PAH?
Improves exercise tolerance and slows symptom progression
How are the endothelin antagonists administered?
Orally
What toxicities are noted with bosentan?
1) Hepatotoxicity
2) Teratogenesis
What drug interaction does bosentan have causing acceleration of their metabolism?
1) Warfarin
2) Oral contraceptives
How does ambrisentan differ from bosentan in terms of toxicities and drug interactions?
1) Does not damage liver
2) Does not accelerate metabolism of warfarin and oral contraceptives
What toxicities are noted with ambrisentan?
Teratogenesis
Which endothelin antagonist is a non-selective agent distinguished by ~18 hr half life that permits once/day dosing?
macitentan
What are the Phosphodiesterase type V Inhibitors?
1) sildenafil
2) tadalafil
(afil)
What is the MOA of the PDE type V inhibitors?
Potentiates cGMP mediated vascular relaxation
What clinical effects are seen with PDE type V inhibitors in the treatment of PAH?
Improves exercise tolerance and slows symptom progression
Which PDE type V inhibitors has the longer half life?
tadalafil
The PDE type V inhibitors can cause a large drop in BP if taken with?
1) α-blockers for hypertension
2) Nitrates for anginal pain
What is the guanylate cyclase sensitizer?
riociguat
What is the MOA of riociguat?
Increased generation of cGMP
What clinical effects are seen with riociguat in the treatment of PAH?
Improves exercise tolerance and slows symptom progression
What should riociguat not be adminstered with?
1) Nitric oxide donors
2) PDE type V inhibitors
What patients are classified as WHO Functional Class I?
WHO FC II?
WHO FC III?
WHO FC IV?
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
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?
1) Ambrisentan and tadalafil
2) Either macitentan, ambrisentan, riociguat, sildenafil or tadalafil
In the Tx of naїve PAH patients with WHO FC III (with rapid disease progression) and WHO FC IV what do you administer?
One of the parenteral prostanoids:
1) IV epoprostenol
2) IV treprostinil
3) SC treprostinil
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?
1) Inhaled prostanoid
2) Oral PDE-5 inhibitor
3) Oral ET-antagonist
What is the most common PAH drug combination?
Ambrisentan and tadalafil
