PAH Flashcards
drug interactions with PDE5i
nitrates, alpha blockers, alcohol, strong CYP3A4 inhibitors/inducers
drug interactions with riociguat
strong CYP and p-gp inhibitors/inducers, PDE5i, non-specific PDEi (theophylline, dipyridamole), smoking, nitrates, antacids
drug interactions with ERAs
strong CYP3A4 and CYP2C19 inhibitors/inducers, warfarin, oral conteraceptives
drug interactions with bosentan
glyburide, cyclosporine
drug interactions with prostacyclins
vasodilators, antiplatelets, anticoagulants
drug interactions with treprostinil
gemfibrozil, rifampin
drug interactions with selexipag
CYP2C8 inhibitors (clopidogrel), inducers (rifampin)
which PDE5 inhibitor has a special renal/hepatic dose or taking ritonavir
tadalafil: half dose
which agents have a REMS program for teratogenicity
bosentan, ambrisentan, macitentin, riociguat
what do you monitor for REMS with the ERAs
pregnancy, LFTs, Hb
which ERA is selective and what is it selective for
ambrisentan (ET-1)
which ERA is lipophilic and tissue-selective
macitentan
which of the newer oral therapies should you avoid if CrCL<15 mL/min or on hemodialysis
riociguat
which of the newer oral therapies should you administer with a high calorie, high fat meal to improve bioavailability
treprostinil diolamine
what are some line-related complications with SQ prostacyclins
injection-site pain and swelling (use topical analgesics)
what are some line-related complications with IV prostacyclins
catheter-related infection, bacteremia, thrombosis (increased risk of gram-negative infection treprostinil>epoprostenol)
what are some adjunctive treatments for PAH
diuretics, digoxin, oxygen, warfarin (out of favor)
explain the difference between pulmonary hypertension and pulmonary arterial hypertension
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
hemodynamic classification of PH
mPAP >20 mmHg
hemodynamic classification of PAH
mPAP>20 mmHg, PAWP <15 mmHg, PVR>3 wood units
name some definite drug-induced causes of PAH
aminorex, fenfluramine, dexfenfluramine, toxic rapeseed oil, benfluorex, methamphetamines, dasatinib (tyrosine kinase inhibitors for cancer)
name some possible drug induced causes of PAH
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
WHO Class I
symptoms at levels of exertion that would limit normal individuals
WHO Class II
symptoms on ordinary exertion
WHO Class III
symptoms on less-than-ordinary exertion
WHO Class IV
symptoms at rest
common symptoms of PAH
dyspnea, fatigue, syncope, palpitations, chest pain, leg edema
describe the pathophysiology of PAH
Increased vascular resistance: vasoconstriction, vascular wall remodeling, in situ thrombosis. Increased vasoconstriction: ET1, TXA2. Decreased vasodilation: PGI2, NO
what are the three pathways for therapeutic targets
endothelin pathway, nitric oxide pathway, prostacyclin pathway
which agents work on the endothelin pathway
ERAs
which agents work on the nitric oxide pathway
PDE5i, riociguat
which agents work on the prostacyclin pathway
prostacyclins and selexipag
explain right ventricular remodeling in PAH
the right heart is strained–> right chambers thicken and enlarge–> blood is forced backwards (regurgitation) through tricuspid valve–> compromises the heart’s pumping capacity
parameters for low european risk assessment
WHO class 1-2, >440 m 6 min walk, NT-proBNP <300, BNP<50, CI>2.5, SvO2 >65%, RAP <8 mmHg
parameters for intermediate european risk assessment
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
parameters for high european risk assessment
WHO class 4, <165 m 6 min walk, NT-proBNP >1400, BNP >300, RAP >14, CI<2, SvO2 <60%
what drugs can you consider for positive response/vasoreactive
CCBs: amlodipine, nifedipine, diltiazem
adverse reactions for PDE5i
headache, dyspepsia, flushing, epistaxis, insomnia, hypotension, visual changes
adverse reactions for riociguat
headache, dizziness, dyspepsia, gastroesophageal reflux, nausea, diarrhea, vomiting, hypotension, anemia, constipation, teratogenicity
adverse reactions for ERAs
headache, flushing, peripheral edema, nasal congestion, sinusitis, transaminitis, liver injury, anemia, teratogenicity
adverse reactions for prostacyclins
nausea, vomiting, diarrhea, flushing, jaw pain, headache, rash, erythema, hypotension, leg pain (inhaled: cough, throat irritation)
adverse reactions for selexipag
headache, diarrhea, jaw pain, nausea, myalgia, vomiting, extremity pain, flushing
which drug has increased risk of gram-negative infection
treprostinil>epoprostenol
give a PDE5i dose
tadalafil 40 mg po daily (20 if renal/hepatic impairment or on ritonavir)
give a ERA dose
ambrisentan 10 mg po daily
give a parenteral prostacyclin dose
epoprostenol 2 ng/kg/min titrated to dose-limiting adverse effects (usual range 20-40 ng/kg/min)
give an inhaled prostacyclin dose
treprostinil 3 breaths QID, titrate by 3 breaths every 1-2 weeks up to 9 breaths QID
give the riociguat dose
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)
when to avoid riociguat
CrCL<15 mL/min
give the treprostinil diolamine extended release dose
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
give the selexipag dose
200 mcg PO bid and uptitrate weekly as tolerated to maximum of 1600 mcg po bid
