CHAPTER 32 PULMONARY ARTERIAL HYPERTENSION
● Characterized by constant high BP in pulmonary
arteries
○ Normal: 8-20 mmHg when a person is
resting
○ PAH: >25 mmHg
● When there is no identifiable cause→
primary/idiopathic PAH
● Secondary: genetic inheritance, connective tissue
diseases, advanced liver disease, HIV
○ Usually derives from left sided heart disease
● Group 3: due to hypoxia or chronic lung diseases
such as COPD, pulmonary fibrosis, or emphysema
● Group 4: chronic thromboembolic PH
○ INR goal 2-3
○ Riociguat is approved for those who cannot
get a thrombectomy
● Group 5: cannot fit any other categories
● Less commonly caused by drugs
○ Cocaine
○ Dasatinib
○ Diazoxide
○ Methamphetamines
○ SSRI use during PG (inc risk in newborns)
○ Weight loss agents (diethylpropion,
lorcaserin, phendimetrazine, phentermine)
● Pathophysiology: imbalance in vasoconstrictor and
vasodilator substances (inc endothelin-1,
thromboxane A2 and dec prostacyclins)
○ In addition, imbalance in cell proliferation
and apoptosis
● Non-drug treatment:
○ <2.4 g/day of Na to help manage volume
status
○ Routine influenza and pneumococcal
pneumonia immunizations
○ Maintain O2 sat >90%
● Treatment:
○ Anticoagulation with warfarin to a goal INR
of 1.5-2.5
○ Loop diuretics for volume overload
○ Digoxin: improve CO or control HR in Afb
○ Refer to PAH clinic for right heart
catheterization to confirm diagnosis and
acute vasoreactivity testing to determine
responsiveness
■ During right heart catheterization,
shorter acting vasodilators such as
nitric oxide, IV epoprostenol, or IV
adenosine are used)
■ If mPAP falls by at least 10 mmHg to
an absolute value less than 40
mmHg, CCB tx should be initiated
● Nifedipine, diltiazem, and
amlodipine→ long acting
● Verapamil
■ Nonresponders are treated with:
● Prostacyclin analogs and
receptor agonists
● Endothelin receptor
antagonists
● PDE5 inhibitors
● sGC stimulators
■ Mostly used for sx tx
■ Prostacyclin analogs specifically IV
epoprostenol dec mortality
● Prostacyclin Analogs: potent vasodilators and
inhibitors of platelet aggregation
○ Drugs such as NSAIDs which dec
prostaglandins should be avoided
○ Warnings: rebound PH
■ Chronic infusions cause sepsis and
bloodstream infections
○ SE: vasodilation rxns, infusion site pain
○ IV are the most potent
○ Avoid interruptions in tx (always provide
back up pumps etc)
○ Avoid large, sudden reductions in dose
○ May inc anti-HTN, antiplatelet, and
anticoagulant effects
● Epoprostenol: (Fiolan) CIVI via central venous
catheter
○ Start at 2 ng/kg/min and inc by 1-2
ng/kg/min in 15 min intervals
○ Usual dose: 25-40 ng/kg/min but can be
titrated higher
○ CI: HF with dec left vent EF
○ Reconstituted Fiolan solutions use ice packs
for stability
○ Veletri is thermostable
● Treprostinil: available as Remodulin CIVI/SQ, tyvaso
inhalation and orenitram PO
○ CI: Child Pugh class C
○ Tablet shell does not dissolve and may
lodge in diverticula
○ Inhalation may cause cough/mouth
irritation
○ Remodulin is thermostable, but may cause
injection site pain
● Iloprost: inhalation
● Selexipag: tablet
● Endothelin Receptor Antagonists: block endothelin
receptors on pulmonary artery smooth muscle cells
(block vasoconstrictor)
○ BBW: embryo-fetal toxicity (need PG test
before tx and monthly thereafter)
○ CI: PG
○ Warnings: hepatotoxicity, dec H/H, fluid
retention
○ SE: HA
● Bosentan: <40 kg: 62.5 mg BID
○ >40 kg: 62.5 mg BID x 4 weeks; then 125 mg
BID
○ BBW: Hepatotoxicity
○ CI: use with cyclosporine or glyburide
○ SE: HSR
○ Can dec effectiveness of OC
○ 3A4 and 2C9 inducer and substrate
● Ambrisentan: 5 mg PO QD may inc to 10 mg QD
after 4 weeks if tolerated
○ CI: idiopathic pulmonary fibrosis
○ Major 3A4 substrate, minor 2C19, and Pgp
substrate
○ Limit dose to 5 mg when taken with
cyclosporine
● Macitentan: 10 mg PO QD
○ Major 3A4 substrate and minor 2C19
substrate
● PDE5 Inhibitors: degrade cGMP which is
responsible for pulmonary vasculature relaxation
and vasodilation
○ CI: use with nitrates or riociguat
○ Warnings: hypotension
○ SE: HA
○ Major substrates of 3A4
● Sildenafil: IV 2.5-10 mg TID
○ PO: 5-20 mg PO TID taken 4-6 hours apart
● Tadalafil: 40 mg daily
○ 20 mg daily if mild/moderate renal
impairment
○ Avoid use in CrCL <30 mL/min
○ Severe hepatic impairment→ avoid
● sCG stimulator: sensitizes sGC to endogenous nitric
oxide and directly stimulates the receptor at a
different binding site to inc cGMP leading to
relaxation and antiproliferative effects
● Riociguat: start with 0.5-1 mg TID inc by 0.5 mg TID
every 2 weeks if SBP >95 mmHg; max dose: 2.5 mg
TID
○ BBW: embryo-fetal toxicity (need PG test
before tx and monthly thereafter)
○ CI: PG and use of PDE5 inhibitors and
nitrates
○ Warnings: hypotension
○ SE: HA
○ Smoking inc clearance
○ Seperate by antacids by 1 hour
○ Major 3A4, 2C8, and Pgp substrate
● PULMONARY FIBROSIS:
○ Caused by:
■ Toxin exposure
■ Medical conditions
■ Drugs: amiodarone, MTX,
nitrofurantoin, sulfasalazine
○ Treat with:
■ Oxygen supplementation
■ Pirfenidone and nintedanib
■ PAH drugs such as sildenafil can be
used off-label
■ Poor prognosis