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Pharma 2- Semmelweis > B-32. Immunophacology III. (antibodies and fusion proteins). > Flashcards

B-32. Immunophacology III. (antibodies and fusion proteins). Flashcards

1
Q

Polyclonal antibody therapies

A
  1. ) Intravenous Immunoglobulin (IVIG)
  2. ) Anti-Rho (D)
  3. ) Polyclonal Antibodies
  4. ) Hyperimmune globulins
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2
Q

Intravenous Immunoglobulin (IVIG) MOA

A
  1. )Neutralizes superantigens and autoantibodies
  2. ) Blocks macrophages FcRs
  3. ) Inhibits complement/immune complex-mediated tissue destruction (isolated from blood of healthy donors)
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3
Q

Indication of Intravenous Immunoglobulin

A
  1. ) Immune Thrombocytopenic Purpura
    - Platelet surface antigen autoantibodies (anti-GP-IIb/IIIa, etc.)
  2. ) Kawasaki disease and other vasculitis
  3. ) Guillain-Barre syndrome
    - Muscle weakness beginning distally (C. jejuni and CMV-related)
  4. ) Polymyositis
    - unknown auto-antigen
  5. )SLE
  6. ) Immunoglobulin deficit
    - as in X-linked agammaglobulinemia etc.
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4
Q

Intravenous Immunoglobulin side effects

A

allergy

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5
Q

Indication for Anti-Rho

A

Given to Rh- mothers after delivery of Rh+ baby to suppress mother’s antibody production

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6
Q

Polyclonal Antibodies includes

A

Anti-lymphocyte and thymocyte globulins

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7
Q

Polyclonal antibodies MOA

A

Polyclonal antibodies from rabbit/horse immunized by human lypho-/thyomocytes that kill/block human lymphocytes

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8
Q

Indication for polyclonal antibodies

A

Transplants prevent acute rejection and used wen rejection of organ is likely.
Also a pretreatment of BM rafts with anti-lymphocyte globulins reduces incidence of GVHD

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9
Q

Side effects of polyclonal antibodies

A
  1. ) Dyspnea
  2. ) Serum sickness
  3. ) Fever and GI issues
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10
Q

What are hyperimmune globulins like? How are they different? What are they used for?

A

Hyperimmune globulins are similar to IVIG but isolated from donors with high titers of Ab specific to certain antigens.
Used for passive immunization of viral infections (CMV, VZV, HBV, rabies) and toxicological issues (dioxin, snake venom, etc.)

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11
Q

-momab means?

A

100% mouse

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12
Q

-ximab means?

A

chimeric; 75% human

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13
Q

-zumab means?

A

95% human

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14
Q

-umab means?

A

100% human

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15
Q

Anti-T cell mAbs names

A
  1. ) Muromonab-CD3

2. ) Basiliximab (Daclizumab, a humanized version)

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16
Q

Muromonab-CD3
MOA?
Indication?
Side effect?

A

Muromonab-CD3 is the first mAb drug; against CD3 (a TCR coreceptor) causing rapid reduction of T cell count.
Indication is kidney transplant, against acute rejection
Side effect is cytokine release syndrome, flu-like, sometime shock

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17
Q 
Basiliximab
MOA?
Indication?
Side effecs?
What is Daclizumab?
A

MOA: Antibody against IL-2 receptor (specific CD-25, the alpha chain of IL-2R) inhibiting T-cell activation
Indication: transplants against acute rejection (less effective than anti-lymphocyte and thymocyte globulins)
Side effects: GI symptoms
Daclizumab, a humanized version, was withdrawn due to enecephalitis risk

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18
Q

Rituximab and Ocrelizumab MOA

A

Binds CD20 B cell antigen (malignant and normal B cells, but not plasma cells). A single treatment reduces B cell count for more than a month via complement and cell mediated B cell destruction.

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19
Q

Indications of Rituximab and Ocrelizumab

A

1.) B-cell lymphomas- of lower malignancy
2.) CLL
3.) Rheumatoid arthritis (2 doses in 2 weeks; again after 6 months break)
4.)Vasculitis
Off-label: treatment resistant AI diseases
5.) MS- ocrelizumab for progressive or relapsing-remitting types

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20
Q

Rituximab and Ocrelizumab side effects

A
  1. ) Infusion reactions- avoidable with steroid, paracetamol+ anti-HA prophylaxis
  2. ) Infections (and increased risk of lymphoma if given with TNF-alpha antagonist)
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21
Q

Other anti-CD20 mAbs

A
  1. ) Obinutuzumab (CLL, follicular lymphoma)
  2. ) Ofatumumab (CLL, FL, diffuse large B-cell lymphoma, RA, MS)
  3. ) Y90-Ibritumomab-tiuxetan
  4. ) Veltuzumab (NHL, non-Hodgkin lymphoma)
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22
Q

Alemtuzumab MOA

A
  • Anti-CD52 mAb.
  • CD52 is a glycoprotein on B-, T-, NK cells and macrophages
  • Possible function as anti-adhesion molecule increased cellular movement.
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23
Q

Alemtuzumab indication

A

Used for MS, no longer used for B-cell CLL (withdrawn)

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24
Q

Side effect of Alemtuzumab

A

myelosuppresion

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25
Q

Anti-TNF alpha drugs

A
  1. ) Etanercept
  2. ) Infliximab
  3. ) Adalimumab
  4. ) Golimumab
  5. ) Certolizumab pegol
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26
Q

Etanercept is a? Binds? Given how and how often?

A
  • A fusion protein of 2 TNF alpha receptor and IgG Fc portions
  • binds free TNF alpha
  • given s.c. 1-2x/week
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27
Q

Infliximab is a? Given how and how often?

A
  • Chimeric mAB

- given i.v. 1-2x/month

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28
Q

Adalimumab is a? Given how and how often?

A
  • human mAb

- given s.c. 1-2x/week

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29
Q

Golimumab is a? Given how and how often?

A
  • human mAb

- given s.c. 1x/month

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30
Q

Certolizumab pegol is a? Given how and how often?

A
  • Humanized Ab Fab fragment bound to PEG

- given s.c. 1-2x/month

31
Q

Indication of infliximab and adalimumab

A
  1. ) RA
  2. ) Ankylosing Spondylitis
  3. ) Psoriasis
  4. ) IBD
  5. ) Juvenile idiopathic arthritis

(In RA, usually combined with MTX)

32
Q

Certolizumab indication

A

Only for RA; milder effect due to no complement activation

In RA, usually combined with MTX

33
Q

Etanercept indication

A

1.) RA
2.) Ankylosing Spondylitis
3.) Psoriasis
4.) Juvenile idiopathic arthritis
NOT IBD because it doesn’t neutralize bound TNF; may worsen symptoms

(In RA, usually combined with MTX)

34
Q

Side effects of Anti-TNF alpha drugs

A
  1. ) Infections- TB, opportunistic, laten viral hepatitis reactivation
  2. ) Injection/infusion reactions
  3. ) Allergy
  4. ) Formation of neutralizing Abs against mAbs is possible, especially with infliximab
35
Q

Drugs affecting IL-17 function

A
  1. ) Secukinumab
  2. ) Ixekizumab
  3. ) Brodalumab
36
Q

Secukinumab and Ixekizumab MOA

A

Anti IL-17 mAb that block pro inflammatory IL-17 prodecued by Th17 cells.
Typically IL-17R activation leads to chemokine production and neutrophil and monocyte migration to inflammatory sites

37
Q

Indication of Secukinumab

A
  1. ) Plaque psoriasis

2. ) Psoriatic arthristis

38
Q

Indications of Ixekizumab

A

Ankylosing spondylitis

39
Q

Side effects of Secukinumab and Ixekizumab

A

Respiratory infections and allergy (rhinitis)

40
Q

Brodalumab MOA

A

Anti-IL 17 receptor mAb which has similar effects to secukinumab and ixekizumab

41
Q

Indications Brodalumab

A

plaque psoriasis

42
Q

Side effects of Brodalumab

A

HA, arthralgia, fatigue, diarrhea, and stomach ache

43
Q

Drugs affecting IL-1 function (3)

A
  1. ) Anakinra

2. ) Canakinumab and Rilonacept

44
Q

MOA of Anakinra

A

IL-1 receptor antagonist; long acting analog of the endogenou IL-1 receptor antagonist peptide

45
Q

Indication of Anakinra

A
  1. ) RA (less effective than TNF blockers)
  2. ) Cryopyrin-associated periodic syndromes (cryopyrin mutation) where cold exposure causes increased IL-1B leading to fever/rash/arthralgia
46
Q

Side effects of Anakinra

A
  1. ) Infections- TB, opportunistic, laten viral hepatitis reactivation
  2. ) Injection/infusion reactions
  3. ) Allergy
  4. ) Formation of neutralizing Abs against mAbs is possible
47
Q

Canakinumab and rilonacept MOA

A

Canakinumab is an anti-IL1B mAb (reilonacept is a dimeric fusion protein of the EC ligand-binding part of the IL1R1 and the Fc portion of the IgG)

48
Q

Integrin inhibitors (2)

A

Natalizumab and Vedolizumab

49
Q

MOA of Natalizumab and Vedolizumab

A

Anti-alpha4 integrin mAb that inhibits docking and extravation of T cells

50
Q
  1. ) What is alpha4beta1-VCAM-1 interaction necessary for?

2. ) What is alpha4beta7-MadCAM-1 interactions necessary for?

A
  1. ) CNS extravasation (MS indication)

2. ) GI tract extravasation (Crohn’s indication)

51
Q

Indication for Natalizumab and Vedolizumab

A

multiple sclerosis and Crohn’s disease (Vedolizumab only acts on GI)

52
Q

Side effects of Natalizumab and Vedolizumab

A
  1. ) Fever, nausea, infection
  2. ) Polyomavirus JC activation
    - Can lead to progressive multifocal leukoencephalopathy (Not in the case of Vedolizumab)
53
Q

Other mAbs drug names (9)

A
  1. ) Tocilizumab
  2. ) Sarilumab
  3. ) Belimumab
  4. ) Ustekinumab
  5. ) Guselkumab
  6. ) Reslizumab
  7. ) Abatacept
  8. ) Omalizumab
  9. ) Eculizumab
54
Q

Tocilizumab and Sarilumab MOA

A

Blocks IL-6 receptor; IL-6 stimulates hepatic acute phase protein synthesis and fever

55
Q

Tocilizumab Indication and kinetics

A

Tocilizumab is used for RA and Juvenile idiopathic arthritis

Given IV monthly

56
Q

Sarilumab Indication and kinetics

A

Sarilumab used only for RA

Given IV/SC 2x/month

57
Q

Tocilizumab and Sarilumab side effects

A

Similar to TNF-alpha inhibition

-Neutropenia and increase lipid levels

58
Q

Belimumab MOA

A

mAb against B-lymphocyte-stimulator-protein (BLyS, BAFF) → inhibits auto-reactive B-cell survival + plasmacytic differentiation; normalizes low complement in SLE

59
Q

Belimumab Indication

60
Q

Belimumab Side effects

A
  1. ) Fever
  2. ) Migraine
  3. ) Arthralgia
  4. ) Leukocytopenia
61
Q

Ustekinumab MOA

A

Ustekinumab binds common p40 subunit of both IL-12 (Th1 formation) + IL-23 (Th17 formation)

62
Q

Ustekinumab indication

A
  1. ) plaque psoriasis
  2. ) psoriatic arthritis
  3. ) Crohn’s
63
Q

Guselkumab MOA and indication

A

Only anti-IL-23 effects; for plaque psoriasis

64
Q

Reslizumab MOA

A

anti-IL-5 mAb → ↓ eosinophil activation (also ↓ B-cell growth and Ig production)

65
Q

Reslizumab Indication

A

bronchial asthma - severe eosinophilic forms

66
Q

Reslizumab side effects

A
  1. ) CK elevation

2. ) allergy

67
Q

Abatacept MOA

A

Abatacept is a fusion protein of CTLA-4 and Fc portion of IgG → binds to CD80/86 on APCs → blocks binding of CD28 on lymphocytes to CD80/86 → ↓ lymphocyte activation
(CD28-CD80/86 binding is normally a “co-stimulatory” signal which occurs along with the MHC-TCR interactions btwn APCs and lymphocytes)

68
Q

Abatacept Indication

A

○ Rheumatoid arthritis
○ JIA - with uveitis
○ Psoriatic arthritis

69
Q

Abatacept Side effects

A

○ HA, infections

○ Neutralizing antibodies - may form against the fusion protein + inhibit it

70
Q

Omalizumab MOA

A

anti-IgE mAb, against Fc portion of IgE → ↓ circulating IgE ≤ 90%

71
Q

Indications for Omalizumab

A

○ Bronchial asthma - severe cases

○ Chronic urticaria

72
Q

Side effects of Omalizumab

A

allergy and local reactions

73
Q

Eculizumab MOA and indication

A

Eculizumab is an anti-C5 mAb → ↓ complement factor 5

Used for paroxysmal nocturnal Hemoglobinuria and HUS; orphan drug

Pharma 2- Semmelweis (43 decks)

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