Pulmonary Hypertension

Question 1

How is pulmonary hypertension

Answer 1

Increase in mean pulmonary arterial pressure greater than 25 mmHg OR 30 mmHg with exercise

Question 2

What are the diagnostic classifications for pulmonary hypertension in neonates

Answer 2

Prenatal or developmental, persistent pulmonary hypertension of the newborn, pediatric heart disease, bronchopulmonary dysplasia, isolated pulmonary arterial hypertension, pediatric lung disease

Question 3

What are the world health organization functional classification of pulmonary hypertension

Answer 3

Class 1: No limitations of physical activity, Class 2: slight limitations of physical activity but comfortable at rest, Class 3:marked limitations of physical activity but comfortable at rest, Class 4: symptoms at rest

Question 4

What are the functional classifications for pulmonary hypertension in children

Answer 4

Class 1: Asymptomatic growing and developing normally with no limitation to activity, Class 2: slight limitation to activity with delayed developmental milestones while comfortable at rest, Class 3A: Marked limitation to activity with regression of learned physical activities with frequent naps compromised comfortability at rest, 3B: The growth is severly compromised with supplemental feelings required, Class 4: unable to do any physical activity and not able to interact with family

Question 5

What are signs and symptoms of pulmonary hypertension

Answer 5

Low oxygen saturation, failure to thrive, lethargic, tachypnea, tachycardia, peripheral edema

Question 6

What is the pathophysiology of PPHN

Answer 6

Failure to achieve normal drop in Pulmonary vascular resistance, decreased/dysfunctional endothelial nitric oxide synthase (eNOS)

Question 7

What is the treatment for PPHN

Answer 7

Inhaled nitric oxide (dilates vessels in the lungs)/ prostacylcin anaglos or sildenafil

Question 8

What is the pathophysiology in pediatrics

Answer 8

Relative imbalances of mediator substances that causes vasoconstriction, pulmonary vscular remodeling and thrombosis

Question 9

What are mediator substances that are increased in pediatric pulmonary hypertension, decreased

Answer 9

Endothelin-1, thromboxane A2, endothelin 1/ prostacyclin and nitric oxide

Question 10

What are the adjunctive therapies that can be used to treat pulmonary hypertension

Answer 10

oxygen, diuretics, and calcium channel blockers, vasopressors, sedation and NMBAs, warfarin

Question 11

What are the potential therapies for pulmonary hypertension

Answer 11

inhaled nitric oxide (iNO), prostacyclin analogs, endothelian-1 antagonist, phosphodiesterase inhibitors

Question 12

What is the MOA of prostacyclin

Answer 12

Bind smooth muscles in the vasculature causing vasodilation and anti-proliferation

Question 13

What are the prostacyclin analogs duration

Answer 13

Epoprostenol treprostinil, Iloprost

Question 14

What is the problem with using epopstenol in pulmonary hypertension

Answer 14

Continous IV infusion (requires long term central venous catheter), not selective and causes vast hypotension

Question 15

What are other side effects

Answer 15

flushing headache nausea diarrhea tachycardia pain tachyphylaxis

Question 16

What are the dosage forms of treprostinil, side effects

Answer 16

Continous subcutaneous infusion, continous IV infusion, inhaled dosage form/ pain and erythema upon injection site

Question 17

Which is the most pulmonary selective, drawback

Answer 17

Iloprost, requires 6 to 9 inhalations

Question 18

T/F: Endothelin 1 causes vasconstriction in the pulmonary vasculature depending on the receptor that is bound

Answer 18

True

Question 19

Where is endothelian A receptors located, what do they cause

Answer 19

Smooth muscle cell/ vasoconstriction, proliferation, cell migration, hypertrophy

Question 20

Where is endothelian B receptors located, what do they cause

Answer 20

Endothelial cells/ inhibition of endothelian 1 production, increased clearance of endothelian 1, increased production of nitrous oxide and PGI2, increased vaso-dilation and anti-proliferation

Question 21

What are the endothelian 1 receptor antagonists

Answer 21

Bosentan and Ambrisentan

Question 22

Which endothelian 1 receptor is contranindicated in pregnancy and has drug-drug interactions, what are the liver enzymes that cause interactions

Answer 22

Bosentan/ CYP2C9: warfarin and oral contraceptives, CYP3A4: ketoconazole, fluvastin, itraconazole

Question 23

What is required for using Bosentan, what changes must be done due to this requirement

Answer 23

Monthly monitoring of LFTs/ If greater than 3 and less than 5 times the upper normal limit: lower the dose for discontinue and monitor every 2 weeks, If greater than 5 and less than 8 times the upper normal limit: stop the bosentan and monitor for two weeks (can re-consider), If greater than 8 times the upper normal limit: Stop bosentan and do not reintroduce

Question 24

What is the pedatric dosing for bosentan

Answer 24

Less than 10kg: 1-2 mg/kg/dose, Greater than or equal to 10kg: 31.25 mg- 62.5 mg once or twice a day

Question 25

How should bosentan be administrated

Answer 25

Wear mask so to not risk teratogenic risk to fetus, should NOT be crushed, dissolve tablets in water just prior to use

Question 26

Which endothelian receptor antagonist that is specific to endothelian receptor 1, other advantage, side effects

Answer 26

Ambrisentan, no hepatic toxicity/ nasal congestion, headache, flushing

Question 27

What are the phosphodiesterase 5 inhibitors used to treat pulmonary hypertension

Answer 27

Sildenafil and Tadalafil

Question 28

What is the MOA of PDE5- inhibitors

Answer 28

Prevent’s cGMP from being broken down by PDE

Question 29

What are the benefits of using sildenafil

Answer 29

lower pulmonary vascular resistance, increase exercise tolerance, available IV (intermittent)