PHARM-restrictive lung disease and pulm. htn Flashcards
Amantadine/Rimantadine MOA
inhibits the M2 ion channel of Influenza A and and reduces viral replicationand duration of symptoms
Zanamivir/Oseltamivir MOA
Influenza A and B Neuraminidase inhibitors, inhibits virus release, limiting the spread of the virus
What 5 categories of drugs would you use to treat ARDS?
- beta-2 agonist, albuterol IV (vasodilate vessels to functional alveoli)
- inhaled NO (vasodilate vessels to functional alveoli
- inhaled prostacylcin (vasodilator)
- corticosteroids (antiinflamm.)
- dietary oil supplementation (anti-inflamm. mod. AA metab.)
what do you give women at risk of delivering before 34 wks?
antenatal corticosteroids, increases synth. of surfactant
what do you give a baby born before 34 wks?
exogenous surfactant (poractant alfa, calfactant, beractant)
what 2 types of drugs do you give to pts with sarcoidosis?
- anti-inflamm. glucocorticoids
2. methotrexate
what are the most potent anti-inflamm. agents and how do they work?
glucocorticoids:
inhibit proinflamm. cytokines (IL-1beta, TNF)
promote production of anti-inflamm. cytokines (IL-10 by mphage and dendritic cells)
promote apoptosis of immune cells
what are some serious adverse effects of chronic corticosteroid use?
suppression of HPA axis osteoporosis, pancreatitis steroid-induced diabetes mellitius cataracts glaucoma psychosis opportunistic infections immunosuppression
How does methotrexate treat sarcoidosis?
dihydrofolate reductase inhibitor
prevents AICAR from becoming FAICAR, leads to buildup of adenosine (has immunosuppressive effects)
What are some important adverse effects of methotrexate therapy?
severe derm. rxns
birth defects and malignant lymphoma
increased risk of infection
pot’l fatal pulm. effects including acute or chronic interstitial pneumonitis and pulmonary fibrosis
How would a doctor use corticosteroid treatment for idiopathic pulmonary fibrosis?
IPF doesn’t respond to corticosteroids so that info could be used to adjust a ddx
what are 2 important profibrogenic cytokines that are released by an altered stromal cell pop. and activated epithelium?
TGF-beta
PDGF
what drugs are shown to be beneficial in idiopathic pulm. fibrosis?
none yet reported
What are 4 drugs that are commonly used to treat Wegener’s?
- Rituximab (on-label use)
- Azathioprine
- Cyclophosphamide
- Corticosteroids
How does rituximab work?
immunosupp. mAb binds to CD20 cell surface on B-cell precursors and mature B cells and are killed 3 ways. ADCC, complement-mediated cytotoxicity, induction of apoptosis
What are some of the important adverse effects of rituximab?
HTN asthenia pruritis urticarial rhinitis arthralgia
MOA azathioprine
DNA and RNA synth. inhib. that also produces immunosupp. possibly by apoptosis of t cells
MOA cyclophosphamide
alkylating agent that also produces B cell and T cell lymphopenia, selective supp. of B-cell activity and decreased Ig secretion
what are some important adverse effects of cyclophosphamide?
hemorrhagic cystitis, neutropenia, thrombocytopenia, bladder cancer, myeloproliferative, lymphoproliferative malignancies
what are the 4 causes of pulmonary artery HTN?
- decreased vasodilators ( PGI2, NO) and increased vasoconstrictors (endothelin-1, TXA2)
- smooth muscle and endothelial cell prolif., propagation, hypertrophy
- thrombosis
- fibrosis
what is the characteristic histologic finding in pulmonary artery hypertension?
plexiform lesions (thickened arterioles as a result of shear stress)
MOA of Prostanoids
induce pulmonary artery vasodilation, slow smooth muscle growth and disrupt platelet aggregation
Name the 3 prostanoids
Epoprostenol
Iloprost
Treprostinil
which prostanoid has the shortest half life?
epoprostenol (continuous IV infusion)
which prostenol has the longest half life?
treprostinil
what is 1 adverse effect common to all the prostanoids?
risk of bleeding, esp. if pt is anticoagulated
also headache
what are some adverse effects of epoprostenol?
dose limiting hypotension
muscle pains
headaches
flushing
what are some adverse effects of iloprost?
cough flushing headaches hypotension HEMOPTOSIS
what are some adverse effects of treprostinil?
rash and pain at injection site headache nausea diarrhea vasodilation jawpain
what are some important drug interactions with treprostinil?
decreased clearance w/ gemfibrozil, increased clearance w/ rifampin
CYP2C8
What is a major disadvantage to using prostanoids that aren’t available orally?
have to have people who can store and reconstitute the drug
very expensive
how do the endothelin-1 receptor antagonists work?
block smooth muscle proliferation and pulm. arterial vasoconstriction
What are the advantages and disadvantages to endothelin-1 receptor antagonists?
advantage: orally active
disadvantage: expensive drugs, Cat. X, bosentan also associated w/ liver and blood toxicities
what are the main adverse effects of bosentan?
elevated LFT, anemia, extensive hepatic metabolism CYP2C9, 3A4
what are the main adverse effects of ambrisentan?
peripheral edema and headache (most common)
fewer liver problems
CYP2C9, 3A4, OATP, P-gp substrate
How do the phosphodiesterase type 5 inhibitors work?
block the destruction of endogenously generated cGMP leading to vasodilation and reduce cellular proliferation
what is the one drug you can’t take with PDE type 5 inhibitors?
nitrates
Name the 2 phosphodiesterase type 5 inhibitors
sildenafil
tadalafil
what is the most common side-effect of PDE type 5 inhibitors?
headache
what are the main side-effects of tadalafil?
headache
backpain, dyspepsia
Change in color vision
CYP3A4 substrate
how do the Calcium channel blockers work?
prevent entry of Calcium into smooth muscle cell during depolarization, vasodilation endures
what is one important thing to remember about CCBs when considering prescribing them to a pt?
it doesn’t work on all pts
What is a vasodilator challenge?
pts receive a carefully escalated dosing rate and the pulm. arterial pressure and CO are monitored to see if the pts respond to the drug. (decrease PAP, w/o decrease in CO)
what are the 3 main CCBs used for pulmonary arterial hypertension?
diltiazem
nifedipine
amlodipine
what is the goal of giving CCB therapy for pts with pulm. HTN?
goal is to achieve NYHA-FC 1 or II after 3-4 months, if not consider alternative therapy
which CCB has the longest half-life?
amlodipine
what is the indication for cyclophosphamide in restrictive lung disease and pulmonary artery HTN
used off label for wegener’s granulomatosis
what is the dose limiting adverse effect of epoprostenol?
hypotension
what is the route of therapy for iloprost?
6-9 inhaled doses a day major hassle
