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Pathology Summaries > IMMUNO: Immunosuppressive therapies > Flashcards

IMMUNO: Immunosuppressive therapies Flashcards

1
Q

What is the MOA of corticosteroids?

A

Glucocorticoids - inhibit phospholipase A2 –x–> arachidonic acid, eicosanoids by COX

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2
Q

Name 2 eicosanoids.

A

Prostaglandins, leukotrienes

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3
Q

What effect do steroids have on

1) phagocytes
2) lymphocytes

A

1) reduce trafficking + enzyme release but increases neutrophil count
2) lymphopenia, less Abs, more apoptosis

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4
Q

Which lymphocyte numbers fall most in corticosteroid use?

A

CD4>CD8>B cell

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5
Q

What bone complication is a severe one associated with corticosteroid use?

A

Avascular necrosis

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6
Q

List 3 cytotoxic/anti-proliferative drugs.

A

Cyclophosphamide
Mycophenolate
Azathioprine

MOA: inhibit DNA synthesis

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7
Q

What infection is associated with cyclophosphamide? What malignancy?

A

PCP
Bladder, haematological, skin (non-melanoma)

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8
Q

Why can you get blood in urine with cyclophosphamide?

A

Causes haemorrhagic cystitis

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9
Q

Which cytotoxic is infection less common with?

A

Azathioprine

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10
Q

Which polymorphism is dangerous with azathioprine use?

A

TPMT - these patients will be unable to metabolise azathioprine

(check FBC after starting)

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11
Q

What is a side effect of all cytotoxic therapies?

A

Bone marrow suppression

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12
Q

Which infection is associated with MMF?

A

PML (JC) and herpes reactivation

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13
Q

What hypersensitivity is treated with plasmapharesis?

A

Type II e.g. Goodpasture and MG or ABO/transplant rejection

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14
Q

What is the MOA of calcineurin inhibitors?

A

reduce IL-2 production and IL-2R expression –> inhibit T cell proliferation and function

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15
Q

What are 3 uses of CIs?

A

Transplants
SLE
Psoriatic arthritis

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16
Q

Give 2 examples of CIs.

A

Tacrolimus
Ciclosporin

(NOT Sirolimus - this is an mTOR inhibitor)

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17
Q

What is the MOA of mTORi? Give one example.

A

Inhibit T cell proliferation and function by blocking signalling. Sometimes called rapalogues because they act like mTORs natural inhibitor rapamycin (macrolide).

e.g. Rapamycin (Sirolimus)

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18
Q

What is the MOA of JAKi/Jakinibs? Give 1 example.

A

Inhibit: JAK-STAT signalling –> gene transcription –> inflammatory cytokines

e.g. TofaCITINIB

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19
Q

What are 3 uses of Jakinibs?

A

RhA
Psoriatic arthritis
Axial spondyloarthritis

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20
Q

What is the MOA of PDE4i? Give one example.

A

Inhibit: PDE4–> cAMP upregulation –> gene transcription via PKA –>cytokine production

e.g. ApreMILAST

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21
Q

What are 2 uses of PDE4 inhibitors?

A

Psoriasis
Psoriatic arthritis

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22
Q

How does abatacept differ from ipilimumab?

A 
Abatacept = CTLA4-Ig --\> aims to suppress 
Ipilimumab = anti-CTLA4 mAb --\> aims to increase immune response
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23
Q

Name an anti-CD25 drug and its aim.

A

Basiliximab - immunosuppress, targets T cells by blocking IL-2 signalling

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24
Q

Name an ati-a4b7 integrin drug and its aim.

A

Vedolizumab - immunosuppress by stopping lymphocyte migration

25
Q

Name a CTLA4-Ig and its aim.

A

Abatacept - immunosuppress, targets T cells

26
Q

What cells do these therapies suppress?
- rabbit ATG, basiliximab, abatacept

A

T cells

27
Q

What cells do these therapies suppress?
- rituximab

A

B cells

28
Q

What cells do these therapies suppress?
-vedolizumab

A

Lymphocyte migration

29
Q

What is a use of ATG? What is its MOA?

A

Allograft rejection - acts by T cell depletion and modulation

30
Q

What is a use of basiliximab/anti-CD25?

A

PROPHYLAXIS of allograft rejection

31
Q

What is the use of Abatacept? How frequently is it given?

A

RhA IV 4 weekly or SC weekly

32
Q

What are the uses of rituximab? What is its MOA?

A

RhA
Lymphoma
SLE

MOA -depletes mature B cells

33
Q

Which RhA therapy only requires 2 doses IV 6-12 monthly?

A

Rituximab

34
Q

What infection is associated with rituximab use? Which conditions can get worse on rituximab?

A

PML (JC)
Cardiovascular conditions worsen

35
Q

What is a use of vedolizumab?

A

IBD - IV every 8 weeks

36
Q

Name 2 complications of vedolizumab use.

A

Hepatotoxicity
Infection - PML

37
Q

What are anti-4/5/13 treatments used for?

A

Eczema and asthma

38
Q

What are anti-IL-6R therapies used for?

A

RhA

39
Q

Which cytokines may be targeted in FMF?

A

TNF-alpha and IL-1 suppression

40
Q

What are anti-IL17/23 treatments used for?

A

Spondyloarthropathies and related conditions i.e. axial spondyloarthritis, psoriasis, psoriatic arthritis, IBD (not IL-17)

41
Q

What are anti-TNF alpha treatments used for?

A

RhA and ankylosing spondylitis
Psoriasis and psoriatic arthritis
IBD
FMF

42
Q

Name a anti-TNF alpha antibody.

A

Infliximab
Adalimumab
Certolizumab
Golimumab

43
Q

What is a specific SE of anti-TNF alpha antibody therapy? What infections are associated?

A

Demyelination
TB, HBV/HCV

44
Q

Name a TNF alpha antagonist. What are its uses?

A

Etanercept - RhA, spondylitis, psoriasis

45
Q

What are the targets of Etanercept?

A

Inhibits TNF ALPHA AND BETA

46
Q

What anti-cytokine for RhA may cause lupus-like conditions?

A

Etanercept

47
Q

What drives IL-1?

A

Inflammasome

48
Q

What treatment is used in Castleman’s disease? What is its MOA?

A

IL-6 blockade
MOA: reduces macrophages, T, B and neutrophil activation.

49
Q

Which anti-cytokine therapy may cause elevated lipids?

A

IL-6 blockade

50
Q

Which T cell responses is IL23 and IL17 involved with?

A

Th17

51
Q

What are the subunits of IL-23 targeted by therapy?

A

p40 and p19

52
Q

What is a SE of targeting IL-23?

A

Infection - TB

53
Q

Which T cell response is important in asthma and eczema?

A

Th2
IL-13 blockade - eczema
IL-5 blockade - asthma
IL4R - both

54
Q

What is OPG?

A

Soluble RANKL decoy which is made by osteoblasts to prevent osteoclast interaction

55
Q

Which cells express RANKL?

A

RANKL = osteoBLASTS

56
Q

Name a RANKL inhibitor.

A

Denosumab

57
Q

Name 2 types of infusion reactions seen with biologics.

A

IgE mediated - urticaria etc
Non-classical type 1 - headache, fevers, myalgias

58
Q

When do infusion site reactions peak?

A

48hrs at the previous site

59
Q

When is risk of PML highest in immunosuppressant use?

A

Multiple biologics used at the same time - JC destroys oligodendrocytes

Pathology Summaries (23 decks)

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