PHARM: Restrictive Lung Disease Flashcards
What are the 3 categories of interstitial restrictive lung disease?
Pneumoconiosis
ARDS/NRDS
Idiopathic
What are the 4 most common pneumoconioses?
Silicosis
CWP
Asbestosis
Berylliosis
How do you treat someone for deposited material (pneumoconiosis)?
NO curative treatment for the deposited material (patients should just avoid further exposure)
True or False: alcohol abuse causes ARDS.
FALSE: it increases the risk of ARDS due to other causes (like sepsis or trauma)
What treatment may help patients with ARDS?
intubation and mechanical ventilation
List the drugs that demonstrate a consistent and unequivocal benefit for ARDS patients.
Trick Question–there are none
List the drugs that are used on ARDS patients (despite the fact they don’t work great).
Beta-2 agonist Inhaled NO Inhaled PGI2 Corticosteroids Dietary oil supplements
Pulmonary vessel vasodilators and anti-inflammatory drugs
What is the most common cause of respiratory failure in newborns?
NRDS
What is NRDS?
Neonatal respiratory distress syndrome arises from surfactant deficiency in immature lungs, leading to increased surface tension, V/Q mismatch, and shunting
What is antenatal corticosteroids?
they are steroids given to mothers at risk of delivery <34 weeks
How do antenatal corticosteroids work?
enhance maturational changes in fetal lung architecture and biochemistry to increase synthesis and release of surfactant (improving neonatal lung function)
What is another treatment (other than antenatal corticosteroids) for NRDS?
exogenous surfactant
Who gets exogenous surfactant?
preterm (<30 week) neonates
List the exogenous surfactant products that are used for NRDS.
Poractant alfa
Calfactant
Beractant
What are the major ingredients in the exogenous surfactants?
DPPC (dipalmitoylphosphatidyl-chlorine)
What are the treatment options available for sarcoidosis?
Glucocorticoids
Methotrexate (off label)
True or false: glucocorticoids are the MOST potent anti-inflammatory drug class.
TRUE
How do glucocorticoids work?
bind to receptors and subsequently modulate transcriptional regulation in the nucleus
What specific genes are increased/decreased by glucocorticoids?
Inhibition of IL-1 and TNF
Promote production of IL-10 and other anti-inflammatory cytokines
True or false: glucocorticoids can promote apoptosis of macrophages, dendritic cells and T cells.
TRUE! This leads to inhibition of the immune response
What is the major side effect of chronic glucocorticoid use?
suppression of the hypothalamic-pituitary-adrenal axis
What is the MOA of methotrexate?
DFR inhibition
How does methotrexate lead to immunosuppression?
Inhibition of AICAR–> FAICAR leads to AICAR accumulation which inhibits AMP deaminase and ADA. This causes an increase in AMP and Adenosine . Adenosine binds to cell receptors and increases levels of cAMP (which cause immunosuppression)
Why is methotrexate not front-line therapy for sarcoidosis?
it has severe side effects
What are some side effects of methotrexate?
dermatologic reactions
birth defects
malignant lymphoma
fatal pulmonary effects
True or false: IPF is treated with potent antiinflammatory drugs.
FALSE: it is not a chronic inflammatory disease so anti-inflammatory drugs yield little to no therapeutic effect!
How can IPF lead to PAH?
activated epithelium due to initial short-lived inflammatory process releases profibrogenic factors that may give rise to the remodeling of blood vessel walls (and can lead to PAH)
True or flase: patients with IPF do not receive as great a benefit from the drugs used for other forms of PAH.
TRUE
What is the gold standard treatment for IPF?
Trick question- there is none!
What is Goodpasture syndrome?
autoimmune disease arising from type II hypersensitivity against the alpha3-chain of type IV collagen in the basement membrane of lungs and kidney
How do you treat Goodpasture syndrome?
plasmapheresis (to reduce the load of auto-antibodies)
What is Wegener’s granulomatosis?
ANCA-positive autoimmune vasculitis primarily in the upper respiratory tract, lungs, and kidneys
What drug is approved to treat Wegener’s granulomatosis?
Rituximab
What is rituximab?
immunosuppressing monoclonal antibody that binds the CD20 cell surface antigen on B-cell precursors and mature B-lymphocytes
How does rituximab kill B-cells?
1) ADCC (recruiting of macrophages and natural killer cells by binding to their Fc-gamma receptors)
2) Complement mediated cytotoxicity (MAC formation)
3) Induction of apoptosis
What are some adverse effects of rituximab?
HTN
asthenia (weakness)
pruritis (itching)
What drugs are used (off-label) for Wegener’s?
Azathioprine
Cyclophosphamide
Corticosteroids
What is the MOA of azathioprine?
DNA and RNA synthesis inhibitor that may cause immunosuppression via facilitation apoptosis of T cells
What are some AEs of azathioprine?
Neoplasms
Leukopenia
Thrombocytopenis
What is the MOA of cyclophosphamide?
alkylating agent that produces B and T cell lymphopenia, selective B-cell suppression, and reduced Ig secretion
What are the AEs of cyclophosphamide?
bladder cancer
malignancy
neutropenia
thrombocytopenia
