Pulm HTN + CF Flashcards
mean pulm arterial pressure >/20 at rest is
pulmonary HTN
pulmonary HTN is measured by
right heart cath
normal right heart cath pressures
8-20
DOE, fatigue, chest pain, syncope, palpitations, swelling in abdomen/legs
pulm HTN
Group 1 of pulmonary HTN
idiopathic, inherited mutations, drug/toxin induced, ass w/ connective tissue disease, HIV, portal HTN, CHD
Group 2
left sided heart disease
group 3
due to chronic lung disease
group 4
from a PE
group 5
unclear multifactor mechanisms
WHO class I
no limitation on activity
WHO class 2
slight limitation
WHO class 3
marked limitation
WHO class 4
inability to carry out any physical activity
use CCBs when
patient responds to vasoactive testing
CCBs to use
nifedipine and amlodipine (smooth + cardiac)
MC ADR: reflex tachy and peripheral edema
dialitazem (cardiac)
MC ADR: bradycardia and peripheral edema
block endothelin receptors, preventing vasoconstriction + promoting vasodilation
endothelial receptor antagonists
ambrisentan, bosentan, macitentan
(preferentially type A receptors)
B + M = dual agents
ambrisentan, bosentan, macitentan are first line for
WHO class II-III, second line in WHO class IV
ambrisentan, bosentan, macitentan can/cannot be used in pregnancy
cannot – women of child bearing age must take monthly pregnancy test
What are ADRs of ambrisentan?
peripheral edema, increased liver enzymes, significant drops in hemoglobin, decreased spermatogenesis
bosentan also has warnings for
hepatotoxicity
- must monitor AST/ALT, dosage adjustments, avoid in elevations
** DIs/ CI in combo with strong 3A4 and 2C9 inhibitors (inducer of those) **
macitentan has much lower incidence of — —
reported hepatotoxicity
macintentan is a — of 3a4
substrate – do not use with strong 3a4 inhibitors or inducers
inhibition of PDE V –> increase in no signlaing –> vasodilation through NO/cGMP –> slow degredation of cGMP –> vasodilation
Phosphodiesterase V inhibitors – sildenafil, tadalafil, vardenafil
sildanefil, taladafil are first line for
WHO Class II-III, second line in WHO class IV
sildenafil caution in patients who have had
MI or stroke
ADRs of sildenafil/tadalafil include
flushing, HA, dyspepsia, visual disturbances, sudden cessation
DIs of sildenafil/tadalafil include
major substrate of 3a4, may enhance hypotensive effects of other BP lowering agents like vasodilators (nitrates) and alpha blockers
Tadalafil needs dosage considerations in
hepatic and renal impairment
Vardenafil has more/less efficacy in class II-IV patients
less but same ADRs
stimulate NO-cGMP pathway to enhance cGMP production + promote vasodilation
guanylate cyclase stimulator
guanylate cyclase stimulator ADRs
tetratogenic
increased mortality if pulm HTN was ass w/ idiopathic interstitial pneumonias
ADRS: significant HOTN, dizziness, dyspepsia, HA
3A4 substrate
smoking can reduce levels!
guanylate cyclase stimulators cannot be combined with what due to significant HOTN?
PDE-V inhibitors
direct vasodilation of pulmonary arteries and inhibition of platelet aggregation
prostacyclin analogs: epoprostenol, iloprost, treprostinil
prostacyclin analogs are used in
WHO III-IV idiopathic PAH
prostacyclin analogs ADRs
half life 3-5 minutes only stable for 8 hours – performed in ICU setting
tachy, flushing, HOTN, dizziness, HA, injection site reaction, anxiety, agitation, N/V, diarrhea, anorexia, myalgia, bone pain
abrupt interruption with prostacyclin analogs can cause
deterioration and death
caution with prostacyclin analogs and drugs that have antiplatelet or blood pressure lowering effects because
CI
Ilioprost is an
inhaled prostacyclin, used for WHO class III-IV
immediate access to medication is always necessary
Ilioprost ADRs
flushing, HOTN, HA, trismus, jaw pain
iloprost could induce what in hyperactive airways
bronchospasm
treprostinil must be administered with what
a high fat meal – use with caution with underlying respiratory disorders and abrupt withdrawal
alcohol increases/decreases absorption of oral dosage of treprostinil
increases
selexipag
prostacyclin IP receptor agonists – selectively agonizes receptors
Selexipag is used in class
II or II patients – avoid use with hepatic impairment
ADRS: flushing, HA, N/V/D, myalgia, jaw pain
greater experience to use
combo therapy
ambition trial:
ambrisentan + tadalafil
Compass-2:
bosentan + sildanefil
Griphon
selexipag + ERA +/- PDE-5i
43% reduction in all cause mortality at 3 years from
initial combo therapy
seraphin
+ macitentan
patent
riociguat added to ERA
respite
riociguat added to PDE-5i
replace
PDE-5i –> riociguat
sequential add on therapy improves outcomes when
monotherapy is insufficient
supportive pulm HTN therapy
diuretics (RV failure/fluid retention)
oxygen
oral anticoagulants
anemia + iron status
other CV agents
chronic cough, frequent lung infections, wheezing and shortness of breath, progressive obstruction, pancreatic insufficiency, steatorrhea, cirrhosis, infertility, digital clubbing, and sinus infections
CF
elevated immunoreactive trypsinogen (IRT) levels on newborn screening
CF
What are dx tips for CF
genetic testing, sweat test, pulmonary function tests
airway clearance techniques
chest physiotherapy
high frequency chest wall oscillation
positive expiratory pressure devices
inhaled treatments for CF
1) bronchodilators = albuterol (relieve bronchospasm + improve airflow)
2) Mucolytics = dornase alfa, hypertonic saline (breaks down mucus)
3) inhaled antibiotics = tobramycin, aztreonam (treat chronic, especially pseudomonas)
4) inhaled steroids
interferes with bacterial protein synthesis, utilized in patients > 6 and p. aeruginosa consistently present, dosed 2x daily in 28 day doses
tobramycin
tobramycin ADRs
bronchospasm, productive cough, rhinitis, oto/nephrotoxicity
monobactam that inhibits bacterial cell wall synthesis by binding penicillin-binding proteins which inhibit peptidoglycan syntehsis in cell walls – > 6 yo patients + p aeruginosa present in culture
3x daily in cycles of 28 days
** pre-treat with bronchodilator **
aztreonam
What are ADRs of aztreonam?
throat pain, cough, nasal congestion, bronchospasm
Oral and IV antibotics for CF
tailored to specific pathogens – combo of beta-lactams, AGs, FQs
cleaves DNA reducing mucous viscosity
dornase alfa
1x daily , > 6 years
caution with FVC <40%
ADRS: cough, pharyngitis, rhinitis, CP, voice disorder
managing CF exacerbations
- abx (2+)
- steroids
- contact precautions
- clean/disinfect nebulizers
- UTD vax
maintaining — —- leads to better FEV1 and survival
normal weight
2-20 = BMI at or above 50th percentile
> 20 female >22, males >23
pancreatic enzyme replacement therapy
combo lipase, amylase, protease (Creon, pancraze)
dissolve in basic pH of duodenal
high doses = colonic stricture
ADRs = HA, abdominal pain, LAD, congestion
CFTR modulators
target underlyng defect in CFTR protein, improving chloride transport
correctors = ivacaftor, lumacaftor
potentiators = ivacfactor, increase function
combo (trikafta)
specific genetic mutations
potentiates epitheleal cell chloride ion transport of defective cell-surface, 2x daily oral therapy, major substrate of 3a4
ivacaftor
ivacaftor administration with — — will increase abdorption
high fat
ivacaftor warnings
risk for hepatotoxicity, increased risk for cataracts in pediatrics
others: HA, diarrhea, abdominal pain, nausea, upper RTI, nasal congestion, oropharyngeal pain
improves conformational stability resulting in increased processing and trafficking, 2x daily oral therapy, with fat foot
lumacaftor
lumacaftor warnings
discontinue if AST/ALT >5x normal limit or >3x with increases in bilirubin
- increases in BP
- menstrual irregularitiy
- increased CK
Also to consider in CF –
gene editing aproaches – CFTR gene
RNA therapies
future directions
other CF meds
beta agonists
oral NSAIDs for <18
azithromycin
inhaled ICS
oral steroids
leukotrine modifiers
inhaled anticholinergics
most CF patients live into their
40s and 50s
