PULMONARY ARTERIAL HYPERTENSION

Question 1

Pulmonary hypertension basics

Classification

Answer 1

PH is characheterized by continuous high blood pressure in the pulmonary arteries. Normal pap is 8 to 20. PH is defined as mean pap >25mmhg
Group 1 - PAH
G 2 - PH due to left heart disease
G3 - PH due to lung disease and/or hypoxia
G4 - chronic thromboembolic pulmonary hypertension
G5 - PH with unclear or multifactorial mechanism

Question 2

Detail classification

Answer 2

Group 1 - Pah (idiopathic, inherited, disease (connective tissue disorders, portal htn, hiv) & toxin, ph in neonates)
Group 2 - pulmonary venous hypertension due to left sided heart disease (left ventricular systolic or diastolic dysfunction, valvular disease, congenital heart disease)
Group 3 - due to lung disease or hypoxia (Copd, pulmonary fibrosis, emphysema)
Group 4 - CTEPH
Group 5 - other reasons (sarcoidosis)

Question 3

drugs that can cause PAH

Answer 3

cocaine
amphetamine/methamphetamine
SSRI during pregnancy cause PAH in newborn
dasatinib
diazoxide
wt loss drugs (lorcaserin, phentermine)

Question 4

patho

Answer 4

1. imbalance between vasoconstrictor (endothelin 1 & thromboxane A2) and vasodilator (prostacyclin 12).
   vasoconstriction - reduced blood flow - increased pressure in pulmonary vasculature
2. imbalance between cell proliferation & apoptosis in pulmonary artery walls.
   increased cell proliferation - wall thickening – forms scar tissue - arteries becomes narrower - increased pressure - difficult for right ventricle to pump blood through pulm arteries to lungs. as a result of working harder right ventricle enlarges - right ventricle failure - death

Question 5

symptoms of PAH

Answer 5

dyspnea, fatigue
chest pain, syncope
edema, tachycardia
raynaud’s phenomenon

Question 6

non drug treatment

Answer 6

salt restriction (<2.4 g/day)
avoid high altitude (hypoxic pulmonary vasoconstriction)
routine immunization (pneumococcal & influenza)
oxygen to maintain saturation >90%

Question 7

drug treatment – general idea

Answer 7

1. prothrombotic state - warfarin (1.5 - 2.5)
2. volume overload - loop diuretics
3. to improve cardiac output & control heart rate in AFIB - digoxin
4. Right heart catheterization - to confirm pah diagnosis & check response to vasoreactivity testing
   during RHC - administer short acting vasodilators (inhaled NO, IV epoprostenol or IV adenosine) if mPAP falls by at least 10mmhg <40mmhhg - start chronic vasodilatory treatment with CCBs (long acting nifedipine, verapamil, diltiazem)
5. others - prostacyclin analogues, prostacyclin receptor agonst, endothelin receptor antagonist, phosphodiesterase 5 inhibitors, soluble guanylate cyclase stimulator

Question 8

prostacyclin analogues - potent vasodilator & inhibit platelet aggregation

Answer 8

in PAH there is reduced prostacyclin synthase - decreased production of prostacyclin 12 (vasodilator & antiproliferative)
IV epoprostenol - decrease mortality
start 2ng/kg/min - increase by 1-2 ng/kg/min in 15min. uusual dose - 25-40 ng/kg/mn or higher
contraindicated in HF with redEF
warning - rebound PH if stopped or reduced dose abruptly, chronic IV infusion increases risk for sepsis & bloodstream infection
SE- vasodilatory reactions, edema, jaw pain, myalgia, tachycardia, tremor, anxiety, infusion site pain
protect from light

Question 9

prostacyclin receptor agonist

Answer 9

Selexipag

200 mcg bd to 1600 mcg bd

Question 10

endothelin receptor antagonists - blocks endothelin receptors block endothelin on pulm artery smooth muscle

Answer 10

bosentan, ambrisentan
embryo-fetal toxicity
bosentan- hepatoxicity, contraindicated with cyclosporine & glyburide, cyp3a4, 2cp substrate
ambrisentan - contraindicated in IPF, cyp3a4,2c19, pgp substrate
Warnings- hepatotoxicity, decrease hb/hct, fluid retention
SE - headache, URTI, flushing, hypotension

Question 10

endothelin receptor antagonists - blocks endothelin receptors block endothelin on pulm artery smooth muscle

Answer 10

bosentan, ambrisentan
embryo-fetal toxicity
bosentan- hepatoxicity, contraindicated with cyclosporine & glyburide, cyp3a4, 2cp substrate
ambrisentan - contraindicated in IPF, cyp3a4,2c19, pgp substrate
Warnings- hepatotoxicity, decrease hb/hct, fluid retention
SE - headache, URTI, flushing, hypotension

Question 11

phosphodiesterase 5 inhibitor - pulmonary vasculature relaxation & vasodilation

Answer 11

1. sildenafil 5-20mg tid
2. tadalafil - 40mg daily. 20mg daily if mild-mod renal/hepatic prob
   contraindication - with nitrates & riociguat
   warnings - hearing loss, NAION, priapism, hypotension
   SE - headache, epistaxis, flushing, back pain, dyspepsia
   when tadalafil is used for pah, alpha blockers are not recommended for bph

Question 12

soluble guanylate cyclase stimulator - relaxation & antiproliferative effect in pulmonary artery smoot muscle cells

Answer 12

Riociguat
embryo-fetal toxicity
contraindicated with PDE5I or nitrates
hypotension, headache, bleeding, dizziness

Question 13

pulmonary fibrosis - scarred & damaged lung tissue

Answer 13

exertional dyspnea with non-productive cough
toxins - asbestos, silica
medical conditions
drugs - amiodarone, bleomycin, dronedarone, methotrexate, nitrofurantoin, sulfasalazine
chronic oxygen therapy
nintedanib, pirfenidone