Drugs for Restrictive Lung Diseases and Pulmonary Artery Hypertension Flashcards Preview

Pulmonary Week 3 > Drugs for Restrictive Lung Diseases and Pulmonary Artery Hypertension > Flashcards

Flashcards in Drugs for Restrictive Lung Diseases and Pulmonary Artery Hypertension Deck (82):
1

Silicosis is a disease typically seen in what patient population?

sand blasters, rock miners, and stone cutters

2

Berylliosis is a disease typically seen in what patient population?

workers of aerospace, nuclear weapon, and electronic industries

3

Silicosis places a patient at increased risk of what?

TB

4

Coal worker’s pneumoconiosis places a patient at increased risk of what?

-right sided heart failure

5

Asbestosis places a patient at increased risk of what?

-malignant mesothelioma
-carcinoma

6

Excessive doses of what drugs have been known to precipitate ARDS?

-aspirin
-cocaine
-tricyclic antidepressants

7

What other thing increases the risk of ARDS?

alcohol abuse (only increases risk of trauma and sepsis, doesn't actually cause it)

8

What are some potential durgs for the treatment of ARDS?

-B2 agonist
-NO
-PGI2 Inhaled
-Corticosteroids
-Dietary oil supplements

9

How is neonatal respiratory distress syndrome treated?

-antenatal corticosteroids (increase release of surfactant)
-exogenous surfactant

10

When is exogenous surfactant administered in patients at risk of NRDS?

pre-30 weeks

11

What products are naturally rich in surfactant proteins B and C and DPPC?

-Poractant alfa
-Calfactant
-Beractant

12

What is the hallmark of sarcoidosis?

young black female with non-caseating granulomas involving MULTIPLE organs

13

Treatment for sarcoidosis?

-glucocorticoids
-methotrexate

14

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

15

What cytokines do glucocorticoids inhibit?

-IL-1B
-TNF

16

What cytokines do glucocorticoids PROMOTE?

IL-10 by macrophages and dendritic cells

17

What are some AEs of chronic glucocorticoid use?

osteoporosis,
pancreatitis, steroid-induced diabetes mellitus, cataracts, glaucoma, psychosis, immunosuppression, weight gain, and skin
atrophy.

18

What infections are particularly common in those chronically taking glucocorticoids?

candidiasis

19

How does Methotrexate work?

DHFR (dihydrofolate reductase) inhibition

and increases adenosine-mediated immunosuppression

20

How does Methotrexate increase adenosine-mediated immunosuppression?

inhibits conversion of GAR to FGAR and AICAR to FAICAR (stronger)

21

What does accumulated AICAR result in?

AMP deaminase and adenosine deaminase (ADA) activity with increased adenosine 5-P and adenosine

22

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

23

What does increase in cAMP cause?

this is the DIRECT cause of immunosuppression

24

T or F. Methotrexate is NOT front-line therapy for its anti-inflammatory
effects.

T.

25

AEs of methotrexate?

-dermatologic rxns
-birth defects
-malignant lymphoma
-pulmonary fibrosis

26

Is idiopathic pulmonary fibrosis a chronic inflammatory disease?

No (even the most potent anti-inflammatory agents don't help)

27

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.)**

28

Why is pulmonary HTN (greater than 25 mmHg) seen in IPF?

remodeling of vessels can occur

29

Drugs for IPF?

pirfenidone [Esbriet] and Nintedanib [Ofev].

30

What does Nintedanib do?

a TKI of VEGF, fibroblast growth factor receptor and PDGF receptor

more effective of the two at reducing exacerbations

31

MOA of Piferidone?

Unknown

32

What is Goodpasture's syndrome?

type II hypersensitivity against the a3 chain of type IV collagen in the BM of lungs and kidney

33

How is GP treated?

plasmapheresis

34

What is Wegener's Granulomatosis?

This is an ANCA-positive autoimmune vasculitis (small-medium vessels), primarily of the
upper respiratory tract, lungs and kidney.

35

Treatment of Wegener's Granulomatosis?

-Rituximab
-Azathioprine
-Cyclophosphamide
-Steroids

36

How does Rituximab work?

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

37

How does Rituximab promote cell death?

1) AB-dependent recruitment of NK and macrophages

2) Complement activation

3) Apoptosis induction

38

AEs of Rituximab?

-HTN
-pruritis/urticaria
-asthenia and arthralgia

39

How does Azathioprine work?

DNA and RNA synthesis inhibitor that also produces immunosuppression,
possibly by facilitating apoptosis of T cell populations.

40

AEs of Azathioprine?

-leukopenia/thrombocytopenia
-neoplasms

41

How does Cyclophosphamide work?

an alkylating agent that also produces (B & T cell) lymphopenia, selective suppression of B-lymphocyte activity and decreased immunoglobulin secretion.

42

AEs of Cyclophosphamide?

-bladder cancer
-myeloproliferative malignancy
-neutropenia

43

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
thromboxane A2);

2) smooth muscle and endothelial cell proliferation, propagation, and hypertrophy (due
to the production of growth inhibitors and mitogenic factors);
3) thrombosis; and

4) fibrosis.

44

What are Plexiform
lesions?

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.

45

The approach to pulmonary HTN therapy is based on what?

severity of disease

46

What are some drug options for pulmonary HTN?

-Prostanoids
-Endothelin-1 receptor antagonists
-Phosphodiesterase Type 5 Inhibitors
-CCBs

47

What are some prostanoids?

-Epoprostenol
-Iloprost
-Treprostinil

48

How do Prostanoids work?

Induce pulmonary artery vasodilation, retard smooth muscle growth and disrupt platelet aggregation

49

How is Epoprostenol given?

continuous IV (T1/2= 3-5 min)

50

AEs of Epoprostenol?

-hypotension
-risk of catheter infection

51

How is Iloprost given?

6-9 inhaled doses/day (T1/2= 25 min)

52

AEs of Iloprost?

-hemoptysis
-cough, flushing, and headaches

53

How is Treprostinil given?

continuous SC or IV infusion (T1/2=4 hrs)

54

AEs of Treprostinil?

-injection site rxn
-jaw pain
-diarrhea

55

DD interactions of Treprostinil?

CYP2C8 drugs (gemfibrozil and rifampin)

56

What is something to always monitor when giving prostanoids?

bleeding risk

57

T or F. Endothelin-1 Receptors antagonists are available PO

T. Advantage over Prostanoids

58

What are the Endothelin-1 Receptors antagonists?

-Bosentan
-Ambrisentan

59

How is Bosentan given?

PO BID

60

AEs of Bosentan?

-liver damage
-anemia
-CYP inducer
-nasopharyngitis

61

How is Ambrisentan given?

PO QD

62

AEs of Ambrisentan?

-peripheral edema
-headache
-CYP2C9, 3A4 metabolism

63

Which Endothelin-1 Receptor antagonist is tetraogenic?

Both

64

How do Phosphodiesterase Type 5 Inhibitors work?

perpetuate endogenously generated cGMP leading to vasodilation and reduce cellular proliferation.

65

Phosphodiesterase Type 5 Inhibitors should never been taken in which patients?

those taking organic nitrates

66

What are the Phosphodiesterase Type 5 Inhibitors?

-Sildenafil
-Tadalafil

67

AEs of Sildenafil?

-headache
-nosebleed
-dizziness with sudden hearing loss
-CYP

68

AEs of Tadalafil?

-headache
-change in color vision
-CYP
-back pain

69

How do CCBs work?

preventing access of Ca2+ into cells during
membrane depolarization, thus blocking the key mediator of smooth muscle contraction

70

Are CCBs effective in pulmonary HTN?

some, but not all patients will benefit (some may undergo a vasodilator challenge before use)

71

What are some drugs used for vasodilatory challenge of pulmonary circulation?

-IV epoprostenol
-adenosine
-inhaled NO

72

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

73

Why even worry about doing a vasodilatory challenge?

limit risk of potentially fatal hemodynamic decompensation with CCBs

74

What are some CCBs?

-Diltiazem
-Nifedipine
-Amlodipine

75

How are CCBs given?

PO

76

AEs of Diltiazem?

-bradycardia, hypotension
-edema

77

AEs of Nifedipine?

-flushing, edema
-heartburn

78

AEs of Amlodipine?

-edema
-fatigue
-hypotension

79

Something to always consider with CCBs?

CYP substrate

80

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.

81

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.

82

Define NYHA-FC I or II

I) No limitations or symptoms associated
with normal physical activity

II) Mild symptoms and/or slight limitation
during normal physical activity