Flashcards in Drugs for Restrictive Lung Diseases and Pulmonary Artery Hypertension Deck (82):
Silicosis is a disease typically seen in what patient population?
sand blasters, rock miners, and stone cutters
Berylliosis is a disease typically seen in what patient population?
workers of aerospace, nuclear weapon, and electronic industries
Silicosis places a patient at increased risk of what?
Coal worker’s pneumoconiosis places a patient at increased risk of what?
-right sided heart failure
Asbestosis places a patient at increased risk of what?
Excessive doses of what drugs have been known to precipitate ARDS?
What other thing increases the risk of ARDS?
alcohol abuse (only increases risk of trauma and sepsis, doesn't actually cause it)
What are some potential durgs for the treatment of ARDS?
-Dietary oil supplements
How is neonatal respiratory distress syndrome treated?
-antenatal corticosteroids (increase release of surfactant)
When is exogenous surfactant administered in patients at risk of NRDS?
What products are naturally rich in surfactant proteins B and C and DPPC?
What is the hallmark of sarcoidosis?
young black female with non-caseating granulomas involving MULTIPLE organs
Treatment for sarcoidosis?
How doe glucocorticoids work?
they act principally by binding to glucocorticoid
receptors and modulating
transcriptional regulation in the nucleus and thus inhibiting pro-inflammatory cytokine production
What cytokines do glucocorticoids inhibit?
What cytokines do glucocorticoids PROMOTE?
IL-10 by macrophages and dendritic cells
What are some AEs of chronic glucocorticoid use?
pancreatitis, steroid-induced diabetes mellitus, cataracts, glaucoma, psychosis, immunosuppression, weight gain, and skin
What infections are particularly common in those chronically taking glucocorticoids?
How does Methotrexate work?
DHFR (dihydrofolate reductase) inhibition
and increases adenosine-mediated immunosuppression
How does Methotrexate increase adenosine-mediated immunosuppression?
inhibits conversion of GAR to FGAR and AICAR to FAICAR (stronger)
What does accumulated AICAR result in?
AMP deaminase and adenosine deaminase (ADA) activity with increased adenosine 5-P and adenosine
What does accumulation of adenosine 5-P and adenosine in the cell cause?
more EXTRAcellular adenosine 5-P and adenosine which binds to A2 receptors yielding an increase cAMP
What does increase in cAMP cause?
this is the DIRECT cause of immunosuppression
T or F. Methotrexate is NOT front-line therapy for its anti-inflammatory
AEs of methotrexate?
Is idiopathic pulmonary fibrosis a chronic inflammatory disease?
No (even the most potent anti-inflammatory agents don't help)
What happens in IPF?
The altered mesenchymal cell phenotype and blockade of apoptosis give rise to an altered stromal cell population and the activated epithelium release a series of profibrogenic factors, TGF-b and PDGF. **This creates a new microenvironment in patchy areas (Other areas remain normal in
structure and environment.)**
Why is pulmonary HTN (greater than 25 mmHg) seen in IPF?
remodeling of vessels can occur
Drugs for IPF?
pirfenidone [Esbriet] and Nintedanib [Ofev].
What does Nintedanib do?
a TKI of VEGF, fibroblast growth factor receptor and PDGF receptor
more effective of the two at reducing exacerbations
MOA of Piferidone?
What is Goodpasture's syndrome?
type II hypersensitivity against the a3 chain of type IV collagen in the BM of lungs and kidney
How is GP treated?
What is Wegener's Granulomatosis?
This is an ANCA-positive autoimmune vasculitis (small-medium vessels), primarily of the
upper respiratory tract, lungs and kidney.
Treatment of Wegener's Granulomatosis?
How does Rituximab work?
a monoclonal antibody that binds the CD20 cell surface antigen on B-cell precursors and mature B-lymphocytes.
How does Rituximab promote cell death?
1) AB-dependent recruitment of NK and macrophages
2) Complement activation
3) Apoptosis induction
AEs of Rituximab?
-asthenia and arthralgia
How does Azathioprine work?
DNA and RNA synthesis inhibitor that also produces immunosuppression,
possibly by facilitating apoptosis of T cell populations.
AEs of Azathioprine?
How does Cyclophosphamide work?
an alkylating agent that also produces (B & T cell) lymphopenia, selective suppression of B-lymphocyte activity and decreased immunoglobulin secretion.
AEs of Cyclophosphamide?
Pulmonary HTN can occur from what four min mechanisms?
1) an imbalance between
vasoconstriction and vasodilation (due to a relative decrease in prostacyclin and NO
production, as well as an increased production of endothelin-1 and a more pronounced presence of
2) smooth muscle and endothelial cell proliferation, propagation, and hypertrophy (due
to the production of growth inhibitors and mitogenic factors);
3) thrombosis; and
What are Plexiform
Thickened arterioles as a result of shear stress- are the histologic hallmark of patients with IPAH or heritable PAH.
These lesions result in proliferation of monoclonal endothelial cells, smooth
muscle cells, and an accumulation of circulating cells (e.g., macrophages and progenitor cells) and
lead to significant obstruction of blood flow.
The approach to pulmonary HTN therapy is based on what?
severity of disease
What are some drug options for pulmonary HTN?
-Endothelin-1 receptor antagonists
-Phosphodiesterase Type 5 Inhibitors
What are some prostanoids?
How do Prostanoids work?
Induce pulmonary artery vasodilation, retard smooth muscle growth and disrupt platelet aggregation
How is Epoprostenol given?
continuous IV (T1/2= 3-5 min)
AEs of Epoprostenol?
-risk of catheter infection
How is Iloprost given?
6-9 inhaled doses/day (T1/2= 25 min)
AEs of Iloprost?
-cough, flushing, and headaches
How is Treprostinil given?
continuous SC or IV infusion (T1/2=4 hrs)
AEs of Treprostinil?
-injection site rxn
DD interactions of Treprostinil?
CYP2C8 drugs (gemfibrozil and rifampin)
What is something to always monitor when giving prostanoids?
T or F. Endothelin-1 Receptors antagonists are available PO
T. Advantage over Prostanoids
What are the Endothelin-1 Receptors antagonists?
How is Bosentan given?
AEs of Bosentan?
How is Ambrisentan given?
AEs of Ambrisentan?
-CYP2C9, 3A4 metabolism
Which Endothelin-1 Receptor antagonist is tetraogenic?
How do Phosphodiesterase Type 5 Inhibitors work?
perpetuate endogenously generated cGMP leading to vasodilation and reduce cellular proliferation.
Phosphodiesterase Type 5 Inhibitors should never been taken in which patients?
those taking organic nitrates
What are the Phosphodiesterase Type 5 Inhibitors?
AEs of Sildenafil?
-dizziness with sudden hearing loss
AEs of Tadalafil?
-change in color vision
How do CCBs work?
preventing access of Ca2+ into cells during
membrane depolarization, thus blocking the key mediator of smooth muscle contraction
Are CCBs effective in pulmonary HTN?
some, but not all patients will benefit (some may undergo a vasodilator challenge before use)
What are some drugs used for vasodilatory challenge of pulmonary circulation?
How does a vasodilatory challenge work?
Patients receive a carefully escalated dosing rate and pulmonary arterial pressure (PAP) and cardiac output (CO) are monitored for 2-3 hr. A
patient who responds positively to a vasodilator challenge (i.e., lower PAP without lower CO) may
then be prescribed certain CCBs
Why even worry about doing a vasodilatory challenge?
limit risk of potentially fatal hemodynamic decompensation with CCBs
What are some CCBs?
How are CCBs given?
AEs of Diltiazem?
AEs of Nifedipine?
AEs of Amlodipine?
Something to always consider with CCBs?
Why is Verapamil avoided with PAH treatment?
Because of its strong negative inotropic properties, which
makes it more likely to induce symptomatic bradycardia than the others.
What is the goal of CCB treatment?
Is for the patient to achieve NYHA-FC I or II
after 3–4 months. If this is not achieved, alternative therapy needs to be considered.