PHARM: Restrictive Lung Disease

Question 1

What are the 3 categories of interstitial restrictive lung disease?

Answer 1

Pneumoconiosis
ARDS/NRDS
Idiopathic

Question 2

What are the 4 most common pneumoconioses?

Answer 2

Silicosis
CWP
Asbestosis
Berylliosis

Question 3

How do you treat someone for deposited material (pneumoconiosis)?

Answer 3

NO curative treatment for the deposited material (patients should just avoid further exposure)

Question 4

True or False: alcohol abuse causes ARDS.

Answer 4

FALSE: it increases the risk of ARDS due to other causes (like sepsis or trauma)

Question 5

What treatment may help patients with ARDS?

Answer 5

intubation and mechanical ventilation

Question 6

List the drugs that demonstrate a consistent and unequivocal benefit for ARDS patients.

Answer 6

Trick Question–there are none

Question 7

List the drugs that are used on ARDS patients (despite the fact they don’t work great).

Answer 7

Beta-2 agonist
Inhaled NO
Inhaled PGI2
Corticosteroids
Dietary oil supplements

Pulmonary vessel vasodilators and anti-inflammatory drugs

Question 8

What is the most common cause of respiratory failure in newborns?

Answer 8

NRDS

Question 9

What is NRDS?

Answer 9

Neonatal respiratory distress syndrome arises from surfactant deficiency in immature lungs, leading to increased surface tension, V/Q mismatch, and shunting

Question 10

What is antenatal corticosteroids?

Answer 10

they are steroids given to mothers at risk of delivery <34 weeks

Question 11

How do antenatal corticosteroids work?

Answer 11

enhance maturational changes in fetal lung architecture and biochemistry to increase synthesis and release of surfactant (improving neonatal lung function)

Question 12

What is another treatment (other than antenatal corticosteroids) for NRDS?

Answer 12

exogenous surfactant

Question 13

Who gets exogenous surfactant?

Answer 13

preterm (<30 week) neonates

Question 14

List the exogenous surfactant products that are used for NRDS.

Answer 14

Poractant alfa
Calfactant
Beractant

Question 15

What are the major ingredients in the exogenous surfactants?

Answer 15

DPPC (dipalmitoylphosphatidyl-chlorine)

Question 16

What are the treatment options available for sarcoidosis?

Answer 16

Glucocorticoids

Methotrexate (off label)

Question 17

True or false: glucocorticoids are the MOST potent anti-inflammatory drug class.

Answer 17

TRUE

Question 18

How do glucocorticoids work?

Answer 18

bind to receptors and subsequently modulate transcriptional regulation in the nucleus

Question 19

What specific genes are increased/decreased by glucocorticoids?

Answer 19

Inhibition of IL-1 and TNF

Promote production of IL-10 and other anti-inflammatory cytokines

Question 20

True or false: glucocorticoids can promote apoptosis of macrophages, dendritic cells and T cells.

Answer 20

TRUE! This leads to inhibition of the immune response

Question 21

What is the major side effect of chronic glucocorticoid use?

Answer 21

suppression of the hypothalamic-pituitary-adrenal axis

Question 22

What is the MOA of methotrexate?

Answer 22

DFR inhibition

Question 23

How does methotrexate lead to immunosuppression?

Answer 23

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)

Question 24

Why is methotrexate not front-line therapy for sarcoidosis?

Answer 24

it has severe side effects

Question 25

What are some side effects of methotrexate?

Answer 25

dermatologic reactions birth defects malignant lymphoma fatal pulmonary effects

Question 26

True or false: IPF is treated with potent antiinflammatory drugs.

Answer 26

FALSE: it is not a chronic inflammatory disease so anti-inflammatory drugs yield little to no therapeutic effect!

Question 27

How can IPF lead to PAH?

Answer 27

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)

Question 28

True or flase: patients with IPF do not receive as great a benefit from the drugs used for other forms of PAH.

Answer 28

TRUE

Question 29

What is the gold standard treatment for IPF?

Answer 29

Trick question- there is none!

Question 30

What is Goodpasture syndrome?

Answer 30

autoimmune disease arising from type II hypersensitivity against the alpha3-chain of type IV collagen in the basement membrane of lungs and kidney

Question 31

How do you treat Goodpasture syndrome?

Answer 31

plasmapheresis (to reduce the load of auto-antibodies)

Question 32

What is Wegener's granulomatosis?

Answer 32

ANCA-positive autoimmune vasculitis primarily in the upper respiratory tract, lungs, and kidneys

Question 33

What drug is approved to treat Wegener's granulomatosis?

Answer 33

Rituximab

Question 34

What is rituximab?

Answer 34

immunosuppressing monoclonal antibody that binds the CD20 cell surface antigen on B-cell precursors and mature B-lymphocytes

Question 35

How does rituximab kill B-cells?

Answer 35

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

Question 36

What are some adverse effects of rituximab?

Answer 36

HTN asthenia (weakness) pruritis (itching)

Question 37

What drugs are used (off-label) for Wegener's?

Answer 37

Azathioprine Cyclophosphamide Corticosteroids

Question 38

What is the MOA of azathioprine?

Answer 38

DNA and RNA synthesis inhibitor that may cause immunosuppression via facilitation apoptosis of T cells

Question 39

What are some AEs of azathioprine?

Answer 39

Neoplasms Leukopenia Thrombocytopenis

Question 40

What is the MOA of cyclophosphamide?

Answer 40

alkylating agent that produces B and T cell lymphopenia, selective B-cell suppression, and reduced Ig secretion

Question 41

What are the AEs of cyclophosphamide?

Answer 41

bladder cancer malignancy neutropenia thrombocytopenia