Chapter 40: Pulmonary Arterial Hypertension

Question 1

Pulmonary arterial hypertension

Answer 1

Characterized by continuous high BP in the pulmonary arteries. Normal PAP ranges from 8-20mmHg
PH is defined as a mean PAP (mPAP) >=25mmHG in the setting of normal fluid status

Question 2

Select drugs that can cause PH

Answer 2

• Cocaine
• SSRI use during pregnancy increases risk of persistent pulmonary hypertension of a newborn (PPHN)
• Weight loss drugs (diethylpropion, lorcaserin, phendimetrazine, phentermine)
• methamphetamines/amphetamine

Question 3

Pathophysiology

Answer 3

PAH stems from an imbalance in vasoconstrictor and vasodilator substances. Vasoconstrictor substances (endothelin-1 and TXA2) are increased and vasodilating substances (prostacyclins) are decrease

Question 4

Heart Failure

Answer 4

is the most common cause of death in people who have PAH

Question 5

Symptoms

Answer 5

• Fatigue
• Dyspnea
• Chest pain
• Syncope
• Edema
• Tachycardia
• Raynaud’s phenomenon

Question 6

Non-drug Tx

Answer 6

• Sodium restricted diet of <2.4gm/day to help manage volume status
• NSAIDs should be avoided
• Vaccination against flu and pneumonia

Question 7

Drug Tx

Answer 7

Responders use CCB (long-acting nifedipine, diltiazem and amlodipine)
Non-responders use prostacyclin analogous and receptor agonists, endothelin receptor antagonists (ERAs), PDE5 inhibitors and/or soluble guanylate cyclase (sGC) stimulator

Question 8

Supportive Drug Tx

Answer 8

• loop diuretics (volume overload)
• digoxin (to improve CO and control HR)
• If warfarin is used INR goal on 1.5-2.5

Question 9

Prostacyclin analouges MOA

Answer 9

-prostacyclin synthase is reduced in PAH causing a decreased production of prostacyclin I2 (a vasodilator with anti-proliferative effects) in pulmonary artery smooth muscle cells.
Prostacyclin analogues are potent vasodilators and inhibitors of platelet aggregation

Question 10

Epoprostenol

Answer 10

Flolan (continuous IV infusion) (prostacyclin analogues)
Dosing: start at 2ng/kg/min
Reconstituted requires ice packs for stability

Question 11

Treprostinil

Answer 11

Remodulin start at 1.25ng/kg/min
(prostacyclin analogues)
protect from light before reconstitution and during infusion

Question 12

Prostacyclin Analogues warnings, SE, and notes

Answer 12

Warnings: vasodilation rxn (hypotension, flushing), rebound PH, chronic IV infusion infections
SE: hypotension, flushing, jaw pain, infusion site pain
Notes: parenteral agents (Flolan, remodulin) are potent vasodilators; avoid interruptions and sudden, large dose reductions

Question 13

Endothelin receptor antagonists

Answer 13

Endothelin is a vasoconstrictor with cellular proliferative effects. ERAs block endothelin receptors on pulmonary artery smooth muscle cells.

Question 14

ERAs warnings, CI, SE

Answer 14

Boxed warnings: teratogenic (women of childbearing age must have a negative pregnancy test prior to initiation and monthly thereafter)
CI: pregnancy
Warnings: hepatotoxicity, decreased Hgb/Hct, fluid retention
SE: headache

Question 15

Bosentan DI

Answer 15

ERA
decreases effectiveness of hormonal contraceptive (at least one if not 2 barrier methods is recommended)
Rems program

Question 16

PDE-5 inhibitor

Answer 16

PDE-5 is responsible for the degradation of cGMP. Increased cGMP concentrations leads to pulmonary vasculature relaxation and vasodilation.

Question 17

Sildenafil

Answer 17

Revatio

Question 18

Tadalafil

Answer 18

Adcirca

Question 19

PDE-5 inhibitors CI, warnings, SE

Answer 19

CI: use with nitrates
Warnings: hearing loss, vision loss, NAION (nonarteritic anterior ischemic optic neuropathy), hypotension, priapism
SE: headache

Question 20

Soluble Guanylate Cyclase Stimulator

Answer 20

sGC is a receptor for the endogenous nitric oxide. Riociguat sensitizes sGC to to endogenous nitrix oxide and directly stimulates the receptor at a different binding site. This increases cGMP leading to relaxation and antiproliferative effects in the pulmonary artery smooth muscle cells.

Question 21

Riociguat

Answer 21

Adempas
Boxed warnings: teratogenic (rems program)
CI: pregnancy, use of PDE-5 inhibitors
Warnings: hypotension
SE: headache

Question 22

Pulmonary Fibrosis

Answer 22

Is scarred and damaged lung tissue. Common presentation of exertional dyspnea and nonproductive dry cough

Question 23

Drugs that can cause pulmonary fibrosis

Answer 23

• Amiodarone/dronedarone
• Bleomycin
• Busulfan
• Carmustine
• Lomustine