PHARM-restrictive lung disease and pulm. htn

Question 1

Amantadine/Rimantadine MOA

Answer 1

inhibits the M2 ion channel of Influenza A and and reduces viral replicationand duration of symptoms

Question 2

Zanamivir/Oseltamivir MOA

Answer 2

Influenza A and B Neuraminidase inhibitors, inhibits virus release, limiting the spread of the virus

Question 3

What 5 categories of drugs would you use to treat ARDS?

Answer 3

1. beta-2 agonist, albuterol IV (vasodilate vessels to functional alveoli)
2. inhaled NO (vasodilate vessels to functional alveoli
3. inhaled prostacylcin (vasodilator)
4. corticosteroids (antiinflamm.)
5. dietary oil supplementation (anti-inflamm. mod. AA metab.)

Question 4

what do you give women at risk of delivering before 34 wks?

Answer 4

antenatal corticosteroids, increases synth. of surfactant

Question 5

what do you give a baby born before 34 wks?

Answer 5

exogenous surfactant (poractant alfa, calfactant, beractant)

Question 6

what 2 types of drugs do you give to pts with sarcoidosis?

Answer 6

1. anti-inflamm. glucocorticoids

2. methotrexate

Question 7

what are the most potent anti-inflamm. agents and how do they work?

Answer 7

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

Question 8

what are some serious adverse effects of chronic corticosteroid use?

Answer 8

suppression of HPA axis
osteoporosis, pancreatitis
steroid-induced diabetes mellitius
cataracts
glaucoma
psychosis
opportunistic infections
immunosuppression

Question 9

How does methotrexate treat sarcoidosis?

Answer 9

dihydrofolate reductase inhibitor

prevents AICAR from becoming FAICAR, leads to buildup of adenosine (has immunosuppressive effects)

Question 10

What are some important adverse effects of methotrexate therapy?

Answer 10

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

Question 11

How would a doctor use corticosteroid treatment for idiopathic pulmonary fibrosis?

Answer 11

IPF doesn’t respond to corticosteroids so that info could be used to adjust a ddx

Question 12

what are 2 important profibrogenic cytokines that are released by an altered stromal cell pop. and activated epithelium?

Answer 12

TGF-beta

PDGF

Question 13

what drugs are shown to be beneficial in idiopathic pulm. fibrosis?

Answer 13

none yet reported

Question 14

What are 4 drugs that are commonly used to treat Wegener’s?

Answer 14

1. Rituximab (on-label use)
2. Azathioprine
3. Cyclophosphamide
4. Corticosteroids

Question 15

How does rituximab work?

Answer 15

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

Question 16

What are some of the important adverse effects of rituximab?

Answer 16

HTN
asthenia
pruritis
urticarial
rhinitis
arthralgia

Question 17

MOA azathioprine

Answer 17

DNA and RNA synth. inhib. that also produces immunosupp. possibly by apoptosis of t cells

Question 18

MOA cyclophosphamide

Answer 18

alkylating agent that also produces B cell and T cell lymphopenia, selective supp. of B-cell activity and decreased Ig secretion

Question 19

what are some important adverse effects of cyclophosphamide?

Answer 19

hemorrhagic cystitis, neutropenia, thrombocytopenia, bladder cancer, myeloproliferative, lymphoproliferative malignancies

Question 20

what are the 4 causes of pulmonary artery HTN?

Answer 20

1. decreased vasodilators ( PGI2, NO) and increased vasoconstrictors (endothelin-1, TXA2)
2. smooth muscle and endothelial cell prolif., propagation, hypertrophy
3. thrombosis
4. fibrosis

Question 21

what is the characteristic histologic finding in pulmonary artery hypertension?

Answer 21

plexiform lesions (thickened arterioles as a result of shear stress)

Question 22

MOA of Prostanoids

Answer 22

induce pulmonary artery vasodilation, slow smooth muscle growth and disrupt platelet aggregation

Question 23

Name the 3 prostanoids

Answer 23

Epoprostenol
Iloprost
Treprostinil

Question 24

which prostanoid has the shortest half life?

Answer 24

epoprostenol (continuous IV infusion)

Question 25

which prostenol has the longest half life?

Answer 25

treprostinil

Question 26

what is 1 adverse effect common to all the prostanoids?

Answer 26

risk of bleeding, esp. if pt is anticoagulated | also headache

Question 27

what are some adverse effects of epoprostenol?

Answer 27

dose limiting hypotension muscle pains headaches flushing

Question 28

what are some adverse effects of iloprost?

Answer 28

``` cough flushing headaches hypotension HEMOPTOSIS ```

Question 29

what are some adverse effects of treprostinil?

Answer 29

``` rash and pain at injection site headache nausea diarrhea vasodilation jawpain ```

Question 30

what are some important drug interactions with treprostinil?

Answer 30

decreased clearance w/ gemfibrozil, increased clearance w/ rifampin CYP2C8

Question 31

What is a major disadvantage to using prostanoids that aren't available orally?

Answer 31

have to have people who can store and reconstitute the drug | very expensive

Question 32

how do the endothelin-1 receptor antagonists work?

Answer 32

block smooth muscle proliferation and pulm. arterial vasoconstriction

Question 33

What are the advantages and disadvantages to endothelin-1 receptor antagonists?

Answer 33

advantage: orally active disadvantage: expensive drugs, Cat. X, bosentan also associated w/ liver and blood toxicities

Question 34

what are the main adverse effects of bosentan?

Answer 34

elevated LFT, anemia, extensive hepatic metabolism CYP2C9, 3A4

Question 35

what are the main adverse effects of ambrisentan?

Answer 35

peripheral edema and headache (most common) fewer liver problems CYP2C9, 3A4, OATP, P-gp substrate

Question 36

How do the phosphodiesterase type 5 inhibitors work?

Answer 36

block the destruction of endogenously generated cGMP leading to vasodilation and reduce cellular proliferation

Question 37

what is the one drug you can't take with PDE type 5 inhibitors?

Answer 37

nitrates

Question 38

Name the 2 phosphodiesterase type 5 inhibitors

Answer 38

sildenafil | tadalafil

Question 39

what is the most common side-effect of PDE type 5 inhibitors?

Answer 39

headache

Question 40

what are the main side-effects of tadalafil?

Answer 40

headache backpain, dyspepsia Change in color vision CYP3A4 substrate

Question 41

how do the Calcium channel blockers work?

Answer 41

prevent entry of Calcium into smooth muscle cell during depolarization, vasodilation endures

Question 42

what is one important thing to remember about CCBs when considering prescribing them to a pt?

Answer 42

it doesn't work on all pts

Question 43

What is a vasodilator challenge?

Answer 43

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)

Question 44

what are the 3 main CCBs used for pulmonary arterial hypertension?

Answer 44

diltiazem nifedipine amlodipine

Question 45

what is the goal of giving CCB therapy for pts with pulm. HTN?

Answer 45

goal is to achieve NYHA-FC 1 or II after 3-4 months, if not consider alternative therapy

Question 46

which CCB has the longest half-life?

Answer 46

amlodipine

Question 47

what is the indication for cyclophosphamide in restrictive lung disease and pulmonary artery HTN

Answer 47

used off label for wegener's granulomatosis

Question 48

what is the dose limiting adverse effect of epoprostenol?

Answer 48

hypotension

Question 49

what is the route of therapy for iloprost?

Answer 49

6-9 inhaled doses a day major hassle