PAH

Question 1

drug interactions with PDE5i

Answer 1

nitrates, alpha blockers, alcohol, strong CYP3A4 inhibitors/inducers

Question 2

drug interactions with riociguat

Answer 2

strong CYP and p-gp inhibitors/inducers, PDE5i, non-specific PDEi (theophylline, dipyridamole), smoking, nitrates, antacids

Question 3

drug interactions with ERAs

Answer 3

strong CYP3A4 and CYP2C19 inhibitors/inducers, warfarin, oral conteraceptives

Question 4

drug interactions with bosentan

Answer 4

glyburide, cyclosporine

Question 5

drug interactions with prostacyclins

Answer 5

vasodilators, antiplatelets, anticoagulants

Question 6

drug interactions with treprostinil

Answer 6

gemfibrozil, rifampin

Question 7

drug interactions with selexipag

Answer 7

CYP2C8 inhibitors (clopidogrel), inducers (rifampin)

Question 8

which PDE5 inhibitor has a special renal/hepatic dose or taking ritonavir

Answer 8

tadalafil: half dose

Question 9

which agents have a REMS program for teratogenicity

Answer 9

bosentan, ambrisentan, macitentin, riociguat

Question 10

what do you monitor for REMS with the ERAs

Answer 10

pregnancy, LFTs, Hb

Question 11

which ERA is selective and what is it selective for

Answer 11

ambrisentan (ET-1)

Question 12

which ERA is lipophilic and tissue-selective

Answer 12

macitentan

Question 13

which of the newer oral therapies should you avoid if CrCL<15 mL/min or on hemodialysis

Answer 13

riociguat

Question 14

which of the newer oral therapies should you administer with a high calorie, high fat meal to improve bioavailability

Answer 14

treprostinil diolamine

Question 15

what are some line-related complications with SQ prostacyclins

Answer 15

injection-site pain and swelling (use topical analgesics)

Question 16

what are some line-related complications with IV prostacyclins

Answer 16

catheter-related infection, bacteremia, thrombosis (increased risk of gram-negative infection treprostinil>epoprostenol)

Question 17

what are some adjunctive treatments for PAH

Answer 17

diuretics, digoxin, oxygen, warfarin (out of favor)

Question 18

explain the difference between pulmonary hypertension and pulmonary arterial hypertension

Answer 18

PH is high blood pressure in the lungs, a general term with many possible underlying causes. PAH is a specific subset of PH, formerly referred to as primary pulmonary hypertension

Question 19

hemodynamic classification of PH

Answer 19

mPAP >20 mmHg

Question 20

hemodynamic classification of PAH

Answer 20

mPAP>20 mmHg, PAWP <15 mmHg, PVR>3 wood units

Question 21

name some definite drug-induced causes of PAH

Answer 21

aminorex, fenfluramine, dexfenfluramine, toxic rapeseed oil, benfluorex, methamphetamines, dasatinib (tyrosine kinase inhibitors for cancer)

Question 22

name some possible drug induced causes of PAH

Answer 22

cocaine, phenylpropanolamine, st john’s wort, chemo, interferon alpha and beta, amphetamines, l-tryptophan, alkylating agents, bosutinib, direct-acting antiviral agents against hepatitis C virus, leflunomide, indirubin

Question 23

WHO Class I

Answer 23

symptoms at levels of exertion that would limit normal individuals

Question 24

WHO Class II

Answer 24

symptoms on ordinary exertion

Question 25

WHO Class III

Answer 25

symptoms on less-than-ordinary exertion

Question 26

WHO Class IV

Answer 26

symptoms at rest

Question 27

common symptoms of PAH

Answer 27

dyspnea, fatigue, syncope, palpitations, chest pain, leg edema

Question 28

describe the pathophysiology of PAH

Answer 28

Increased vascular resistance: vasoconstriction, vascular wall remodeling, in situ thrombosis. Increased vasoconstriction: ET1, TXA2. Decreased vasodilation: PGI2, NO

Question 29

what are the three pathways for therapeutic targets

Answer 29

endothelin pathway, nitric oxide pathway, prostacyclin pathway

Question 30

which agents work on the endothelin pathway

Answer 30

ERAs

Question 31

which agents work on the nitric oxide pathway

Answer 31

PDE5i, riociguat

Question 32

which agents work on the prostacyclin pathway

Answer 32

prostacyclins and selexipag

Question 33

explain right ventricular remodeling in PAH

Answer 33

the right heart is strained--> right chambers thicken and enlarge--> blood is forced backwards (regurgitation) through tricuspid valve--> compromises the heart's pumping capacity

Question 34

parameters for low european risk assessment

Answer 34

WHO class 1-2, >440 m 6 min walk, NT-proBNP <300, BNP<50, CI>2.5, SvO2 >65%, RAP <8 mmHg

Question 35

parameters for intermediate european risk assessment

Answer 35

WHO class 3, 165-440 m 6 min walk, NT-proBNP 300-1400 ng/L, BNP 50-200 ng/L, SVO2 60-65%, CI 2-2.4, RAP 8-14 mmHg

Question 36

parameters for high european risk assessment

Answer 36

WHO class 4, <165 m 6 min walk, NT-proBNP >1400, BNP >300, RAP >14, CI<2, SvO2 <60%

Question 37

what drugs can you consider for positive response/vasoreactive

Answer 37

CCBs: amlodipine, nifedipine, diltiazem

Question 38

adverse reactions for PDE5i

Answer 38

headache, dyspepsia, flushing, epistaxis, insomnia, hypotension, visual changes

Question 39

adverse reactions for riociguat

Answer 39

headache, dizziness, dyspepsia, gastroesophageal reflux, nausea, diarrhea, vomiting, hypotension, anemia, constipation, teratogenicity

Question 40

adverse reactions for ERAs

Answer 40

headache, flushing, peripheral edema, nasal congestion, sinusitis, transaminitis, liver injury, anemia, teratogenicity

Question 41

adverse reactions for prostacyclins

Answer 41

nausea, vomiting, diarrhea, flushing, jaw pain, headache, rash, erythema, hypotension, leg pain (inhaled: cough, throat irritation)

Question 42

adverse reactions for selexipag

Answer 42

headache, diarrhea, jaw pain, nausea, myalgia, vomiting, extremity pain, flushing

Question 43

which drug has increased risk of gram-negative infection

Answer 43

treprostinil>epoprostenol

Question 44

give a PDE5i dose

Answer 44

tadalafil 40 mg po daily (20 if renal/hepatic impairment or on ritonavir)

Question 45

give a ERA dose

Answer 45

ambrisentan 10 mg po daily

Question 46

give a parenteral prostacyclin dose

Answer 46

epoprostenol 2 ng/kg/min titrated to dose-limiting adverse effects (usual range 20-40 ng/kg/min)

Question 47

give an inhaled prostacyclin dose

Answer 47

treprostinil 3 breaths QID, titrate by 3 breaths every 1-2 weeks up to 9 breaths QID

Question 48

give the riociguat dose

Answer 48

1 mg PO tid, titrate in 0.5 mg increments every 2 weeks up to 2.5 mg PO tid (start at 0.5 if hypotension risk or strong CYP and p-gp inhibitors)

Question 49

when to avoid riociguat

Answer 49

CrCL<15 mL/min

Question 50

give the treprostinil diolamine extended release dose

Answer 50

initiate 0.25 mg PO bid or 0.125 mg tid, titrate by 0.125-0.5 mg PO increments bid to tid every 3-4 days or longer

Question 51

give the selexipag dose

Answer 51

200 mcg PO bid and uptitrate weekly as tolerated to maximum of 1600 mcg po bid