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Flashcards in Pulmonary artery hypertension Deck (44):
1

What is PAH

restricted blood flow through pulmonary circulation, increased pulmonary pressure, PVR, low flow, high resistance

2

Normal Mean pulmonary arterial pressure

14+/- 3mmHg

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PAH classified by

mPAP>25mmHg at rest and >30 w/ exercise, PCWP

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Group 1 PAH

idiopathic, familial, associated with drugs, toxins, congenital heart disease, portal htn, HIV, shistosomiasis, connective tissue disease

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Group 2 PAH

left sided hf, valvular dysfunction

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Group 3 PAH

respiratory disease, COPD or interstitial lung disease

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Group 4 PAH

thromboembolic disease

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Group 5 PAH

Miscellaneous

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Approved drugs are aimed to target

Group 1

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Drugs that can cause PAH

cocaine, amphetamines, fen-fen

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3 mechanisms of vascular injury to pulmonary arterioles

vasoconstriction, platelet dysfunction leading to thrombosis, vascular smooth muscle hypertrophy proliferation and hyperplasia

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Endothlial dysfunction results from and imbalance mediators

dec nitric oxide synthase, dec prostacyclin, and inc endothelin 1 all lead to vasoconstriction

13

Non specific clinical features

dyspnea, fatigue, exertional syncope/angina, cx pain, palpitations, peripheral edema

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Severe signs of PAH, usually when diagnosed

hepatomegaly, peripheral edema, weight gain from fluid, ascites, JVD

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Ways to determine severity

effort tolerance, 6MWT (

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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

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Class 1 PAH

no resulting limitation or physical activity

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Class 2 PAH

slight limitation of physical activity, comfortable at rest

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Class 3 PAH

marked limitation of physical activity, comfortable at rest, little activity cause symptoms

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Class 4 PAH

inability to carry out any physical activity w/out sx, right side HF, fatigue at rest

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Supportive care

diuretics, anticoagulation (1.5-2.5 INR), supplemental O2, digoxin

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CCBs

only systemic anti-HTN to show benefit, high dose in absence of HF, Diltiazem if pt tachy, nifedipine or amlodipine if brady

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PAH specific therapies

Prostanoids, endothelin recepto-1 antagonists, PDE-5 inhibitors

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Prostanoids

Epoprostenol (Flolan, Veletri), Treprostinil (Tyvaso, Remodulin), Iloprost (Ventavis)

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Endothelin Receptor-1 antagonist

Bosentan (Tracleer), Ambrisentan (Letairis)

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PDE-5 inhibitors

Sildinafil (Ravatio), Tadalafil (Adcirca)

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MOA of prostanoids

strong vasodilator of all vascular beds and potent endogenous inhibitor of platelet aggregation

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Adverse effects of Epoprostenol (Flolan, Veletri)

flushing, HA, hypotension, pump malfunction, catheter related infections, thrombosis

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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

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Epoprostenol (Flolan, Veletri) negatives

very short T1/2 (3-5 min), must be constituted, must be kept cool

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Treprostinil (Remodulin) ADRs

Pain at injection sight, flushing, HA, hypotension

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Iloprost (Ventavis)

administered inhalation by I-neb or Prodose, 6-9 times per day, treatment takes 10 mins, ADRs are minimal

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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

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Treprostinil (Tyvaso) inhaler

approved in 2009, effective as Iloprost, longer half life, faster administration, similar ADRs

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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)

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Ambrisentan (Letairis)

Selective ETa receptor agonist, functional class 2-3, oral, less liver toxicity, risk of teratogenicity, anemia, restricted access (LEAP)

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MOA of endothelin-1 receptor antagonist

inhibit vasoconstriction and smooth muscle proliferation caused by endothelin, weak efficacy compared to Prostanoids

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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

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PDE-5 inhibitors MOA

inhibit degradation of cGMP via PDE-5 resulting in inc levels of vasodilatory NO

40

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

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Functional Class 2 treatment

Ambrisentan, Bosentan, Sildinafil and Tadalafil

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Functional Class 3 treatment

Ambrisentan, Bosentan, Epoprostenol, Treprostinil, iloprost, sildinafil, tadalafil

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Functional Class 4 treatment

Epoprostenol, Treprostinil, Iloprost

44

If single therapy doesn't work

can combine classes, but then will need trial septostomy and lung ransplant