Pulmonary artery hypertension

Question 1

What is PAH

Answer 1

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

Question 2

Normal Mean pulmonary arterial pressure

Answer 2

14+/- 3mmHg

Question 3

PAH classified by

Answer 3

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

Question 4

Group 1 PAH

Answer 4

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

Question 5

Group 2 PAH

Answer 5

left sided hf, valvular dysfunction

Question 6

Group 3 PAH

Answer 6

respiratory disease, COPD or interstitial lung disease

Question 7

Group 4 PAH

Answer 7

thromboembolic disease

Question 8

Group 5 PAH

Answer 8

Miscellaneous

Question 9

Approved drugs are aimed to target

Answer 9

Group 1

Question 10

Drugs that can cause PAH

Answer 10

cocaine, amphetamines, fen-fen

Question 11

3 mechanisms of vascular injury to pulmonary arterioles

Answer 11

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

Question 12

Endothlial dysfunction results from and imbalance mediators

Answer 12

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

Question 13

Non specific clinical features

Answer 13

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

Question 14

Severe signs of PAH, usually when diagnosed

Answer 14

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

Question 15

Ways to determine severity

Answer 15

effort tolerance, 6MWT (

Question 16

Patients who respond to vasodilator test

Answer 16

dec of 10 mmHg from baseline and inc or unchanged CI are considered responders and are eligible for treatment with CCBs

Question 17

Class 1 PAH

Answer 17

no resulting limitation or physical activity

Question 18

Class 2 PAH

Answer 18

slight limitation of physical activity, comfortable at rest

Question 19

Class 3 PAH

Answer 19

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

Question 20

Class 4 PAH

Answer 20

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

Question 21

Supportive care

Answer 21

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

Question 22

CCBs

Answer 22

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

Question 23

PAH specific therapies

Answer 23

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

Question 24

Prostanoids

Answer 24

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

Question 25

Endothelin Receptor-1 antagonist

Answer 25

Bosentan (Tracleer), Ambrisentan (Letairis)

Question 26

PDE-5 inhibitors

Answer 26

Sildinafil (Ravatio), Tadalafil (Adcirca)

Question 27

MOA of prostanoids

Answer 27

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

Question 28

Adverse effects of Epoprostenol (Flolan, Veletri)

Answer 28

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

Question 29

Treprostinil (Remodulin)

Answer 29

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

Question 30

Epoprostenol (Flolan, Veletri) negatives

Answer 30

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

Question 31

Treprostinil (Remodulin) ADRs

Answer 31

Pain at injection sight, flushing, HA, hypotension

Question 32

Iloprost (Ventavis)

Answer 32

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

Question 33

Difference between I-neb and Prodose

Answer 33

I-neb is hand-held, battery operated, 2 methods of inhalation, $$$, requires daily cleaning, Prodose is cheaper and less portable

Question 34

Treprostinil (Tyvaso) inhaler

Answer 34

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

Question 35

Bosentan (Tracleer)

Answer 35

non selective competitive antagonist for ETa and ETb, functional class 2-4, oral, inc AST/ALT, anemia, risk of tratogenicity, restricted access (TAP)

Question 36

Ambrisentan (Letairis)

Answer 36

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

Question 37

MOA of endothelin-1 receptor antagonist

Answer 37

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

Question 38

Negatives of ERAs

Answer 38

monitor LFTs, HCG, both contraindicated in pregnancy, and Bosentan is substrate of CYP2C9 and 3A4 and cannot be given with cyclosporine or glyburide

Question 39

PDE-5 inhibitors MOA

Answer 39

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

Question 40

Sildinafil vs Tadalafil

Answer 40

Sildinafil approved for 2-3, DI with CYP2C9 and 3A4, Tadalafil approved for 2-3, DI with CYP3A4 and renal hepatic adjust

Question 41

Functional Class 2 treatment

Answer 41

Ambrisentan, Bosentan, Sildinafil and Tadalafil

Question 42

Functional Class 3 treatment

Answer 42

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

Question 43

Functional Class 4 treatment

Answer 43

Epoprostenol, Treprostinil, Iloprost

Question 44

If single therapy doesn't work

Answer 44

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