Pulmonary artery hypertension Flashcards
What is PAH
restricted blood flow through pulmonary circulation, increased pulmonary pressure, PVR, low flow, high resistance
Normal Mean pulmonary arterial pressure
14+/- 3mmHg
PAH classified by
mPAP>25mmHg at rest and >30 w/ exercise, PCWP
Group 1 PAH
idiopathic, familial, associated with drugs, toxins, congenital heart disease, portal htn, HIV, shistosomiasis, connective tissue disease
Group 2 PAH
left sided hf, valvular dysfunction
Group 3 PAH
respiratory disease, COPD or interstitial lung disease
Group 4 PAH
thromboembolic disease
Group 5 PAH
Miscellaneous
Approved drugs are aimed to target
Group 1
Drugs that can cause PAH
cocaine, amphetamines, fen-fen
3 mechanisms of vascular injury to pulmonary arterioles
vasoconstriction, platelet dysfunction leading to thrombosis, vascular smooth muscle hypertrophy proliferation and hyperplasia
Endothlial dysfunction results from and imbalance mediators
dec nitric oxide synthase, dec prostacyclin, and inc endothelin 1 all lead to vasoconstriction
Non specific clinical features
dyspnea, fatigue, exertional syncope/angina, cx pain, palpitations, peripheral edema
Severe signs of PAH, usually when diagnosed
hepatomegaly, peripheral edema, weight gain from fluid, ascites, JVD
Ways to determine severity
effort tolerance, 6MWT (
Patients who respond to vasodilator test
dec of 10 mmHg from baseline and inc or unchanged CI are considered responders and are eligible for treatment with CCBs
Class 1 PAH
no resulting limitation or physical activity
Class 2 PAH
slight limitation of physical activity, comfortable at rest
Class 3 PAH
marked limitation of physical activity, comfortable at rest, little activity cause symptoms
Class 4 PAH
inability to carry out any physical activity w/out sx, right side HF, fatigue at rest
Supportive care
diuretics, anticoagulation (1.5-2.5 INR), supplemental O2, digoxin
CCBs
only systemic anti-HTN to show benefit, high dose in absence of HF, Diltiazem if pt tachy, nifedipine or amlodipine if brady
PAH specific therapies
Prostanoids, endothelin recepto-1 antagonists, PDE-5 inhibitors
Prostanoids
Epoprostenol (Flolan, Veletri), Treprostinil (Tyvaso, Remodulin), Iloprost (Ventavis)
Endothelin Receptor-1 antagonist
Bosentan (Tracleer), Ambrisentan (Letairis)
PDE-5 inhibitors
Sildinafil (Ravatio), Tadalafil (Adcirca)
MOA of prostanoids
strong vasodilator of all vascular beds and potent endogenous inhibitor of platelet aggregation
Adverse effects of Epoprostenol (Flolan, Veletri)
flushing, HA, hypotension, pump malfunction, catheter related infections, thrombosis
Treprostinil (Remodulin)
develop in response to Epoprostenol, continuous SC* or IV, T1/2 is 4 hours and does not require protection from light or heat, no reconstitution
Epoprostenol (Flolan, Veletri) negatives
very short T1/2 (3-5 min), must be constituted, must be kept cool
Treprostinil (Remodulin) ADRs
Pain at injection sight, flushing, HA, hypotension
Iloprost (Ventavis)
administered inhalation by I-neb or Prodose, 6-9 times per day, treatment takes 10 mins, ADRs are minimal
Difference between I-neb and Prodose
I-neb is hand-held, battery operated, 2 methods of inhalation, $$$, requires daily cleaning, Prodose is cheaper and less portable
Treprostinil (Tyvaso) inhaler
approved in 2009, effective as Iloprost, longer half life, faster administration, similar ADRs
Bosentan (Tracleer)
non selective competitive antagonist for ETa and ETb, functional class 2-4, oral, inc AST/ALT, anemia, risk of tratogenicity, restricted access (TAP)
Ambrisentan (Letairis)
Selective ETa receptor agonist, functional class 2-3, oral, less liver toxicity, risk of teratogenicity, anemia, restricted access (LEAP)
MOA of endothelin-1 receptor antagonist
inhibit vasoconstriction and smooth muscle proliferation caused by endothelin, weak efficacy compared to Prostanoids
Negatives of ERAs
monitor LFTs, HCG, both contraindicated in pregnancy, and Bosentan is substrate of CYP2C9 and 3A4 and cannot be given with cyclosporine or glyburide
PDE-5 inhibitors MOA
inhibit degradation of cGMP via PDE-5 resulting in inc levels of vasodilatory NO
Sildinafil vs Tadalafil
Sildinafil approved for 2-3, DI with CYP2C9 and 3A4, Tadalafil approved for 2-3, DI with CYP3A4 and renal hepatic adjust
Functional Class 2 treatment
Ambrisentan, Bosentan, Sildinafil and Tadalafil
Functional Class 3 treatment
Ambrisentan, Bosentan, Epoprostenol, Treprostinil, iloprost, sildinafil, tadalafil
Functional Class 4 treatment
Epoprostenol, Treprostinil, Iloprost
If single therapy doesn’t work
can combine classes, but then will need trial septostomy and lung ransplant
