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BPT Flashcards > Immunomodulators > Flashcards

Immunomodulators Flashcards

1
Q

Pembrolizumab MOA

A

Humanised PD-1 inhibitor

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1
Q

Examples of PD-L1 inhibitors

A

Durvalumab
Atezolimumab

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2
Q

Specific side effects of PD-1 and PD-L1 inhibitors

A

Increased risk of autoimmune conditions i.e. pneumonitis, dermatitis

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3
Q

Alemtuzumab MOA

A

CD52 inhibitor - used for MS and CLL
Presents on B and T cells - depletes both lymphoid cell lines

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4
Q

Alemtuzumab side effects

A

Autoimmune conditions i.e. autoimmune thyroiditis, ITP

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5
Q

Examples of anti-TNF alpha agents

A

Chimeric - Infliximab
Humanised - Adalimumab, Golimumab, certolizumab

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6
Q

Indications for anti-TNA-alpha

A

Refractory therapy for chronic inflammatory systemic diseases
- RA
- Ankylosing spondylitis
- Psoriasis, PA
- CD, UC

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7
Q

Side effects of TNA-a inhibitors

A

Severe infections
Reactivation of prior infections
Drug-induced lupus

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8
Q

MOA and side effects of etanercept

A

Fusion protein synthesised by recombinant DNA
Decoy receptor that binds to TNF-A and IgG1 Fc

Severe infections
Reactivation of prior infections
Drug induced lupus

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9
Q

MOA and side effects of rituximab

A

Chimeric CD20 inhibitor

Reactivation of JC virus infection –> PML
Infusion reaction

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10
Q

Rituximab uses

A

RA
ITP
TTP
MS
AIHA
NHL
Symptomatic Waldenstrom macroglobulinaemia

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11
Q

MOA, use and S/E of natalizumab

A

Humanised alpha-4-integrin inhibitor

Escalation therapy of MS
Crohn’s disease

Reactivation of latent JC virus
Infusion reactions

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12
Q

MOA and uses of cetuximab

A

Chimeric EGFR inhibitor

Used for
CRC stage IV, wide type KRAS
Head and neck cancer

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13
Q

MOA and uses of panitumumab

A

Humanised EGFR inhibitor

Used for
CRC stage IV, wide type KRAS
Head and neck cancer

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14
Q

MOA of tocilizumab

A

Humanised IL-6 inhibitor

Used for
GCA
Juvenile idiopathic arthritis
RA
Severe COVID-19

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15
Q

MOA of secukinumab

A

Human IL-17A inhibitor
Decreases inflammatory cell migration, B cell differentiation and activation of hepatic acute phase response

Used for
Psoriasis
Psoriatic arthritis

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16
Q

MOA of ixekizumab

A

Humanised IL-17A inhibitor

Used for psoriasis
Psoriatic arthritis

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17
Q

MOA of brodalumab

A

Human IL-17R inhibitor

Used for treatment-refractory psoriasis

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18
Q

MOA of vedolizumab

A

Humanised a4B7 integrin inhibitor

Used for
CD
UC

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19
Q

MOA of ustekinumab

A

Human IL12/23 inhibitor

Used for
Psoriasis, PsA
Crohn’s

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20
Q

MOA of omalizumab

A

Humanised
Acts on unbound serum IgE

Severe persistent allergic asthma (resistant to inhaled steroids and LABAs) with increased IgE

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21
Q

SE of omalizumab

A

Arthralgia
Fatigue, dizziness
Pruritus, dermatitis

22
Q

MOA, use and side effects of abciximab

A

Chimeric antagonist of GPIIb/IIIa receptors

Antiplatelet agent, used for patients undergoing PCI

Causes acute thrombocytopenia, haemorrhage

23
Q

Muromonab MOA, use and side effects

A

Anti-CD3 (from T cells)
Used for steroid-resistant acute rejection post-transplantation

Causes cytokine storm

24
Q

Basiliximab MOA, use and side effects

A

Chimeric anti-CD25 (targets alpha chain of IL-2 receptor of T cells)

Used for
Escalation therapy of MS
Formerly used for prevention of kidney rejection post transplantation

Causes tremors, hypertension, oedema

25
Q

Daclizumab MOA

A

Humanised anti-CD25
Similar use and side effect profile to basiliximab (MS, causes tremor, HTN and oedema)

26
Q

Trastuzumab MOA, use and side effects

A

Humanised HER2/neu tyrosine kinase receptor
Inhibits HER2-initiated cellular signalling and antibody-dependent cytotoxicity

Causes dilated cardiomyopathy

27
Q

Bevacizumab MOA, uses and side effects

A

Humanised VEGF inhibitor (inhibits angiogenesis)

Used in
Neovascular age-related macular degeneration
Proliferative diabetic retinopathy
Solid tumours
- nSCLC
- CRC
- RCC

Causes haemorrhages, GI bleeding, wound healing, thrombosis

28
Q

Eculizumab MOA, uses and side effects

A

Humanised complement protein C5 inhibitor

Used in PNH and HUS

Increased risk of infection with encapsulated bacteria e.g. N meningitidis

29
Q

Ipilimumab MOA, uses and side effects

A

Human CTLA-4 inhibitor

Melanoma, lymphoma, lung cancer, RCC, urothelial carcinoma, prostate cancer

Increased risk of autoimmune conditions

30
Q

Guselkumab MOA and uses

A

Human IL-23 inhibitor
Used for psoriasis

Increased risk of autoimmune conditions

31
Q

Examples of PD-1 inhibitor and uses

A

Pembrolizumab
Nivolumab
Cemiplimab

RCC, urothelial carcinoma, nSCLC, Melanoma

32
Q

Cyclosporine side effects

A

Nephrotoxicity
Gingival hyperplasia
Hypertrichosis and hirsutism
Diabetogenic effect - hyperuricaemia, hyperlipidaemia, elevated liver enzymes
Increase in malignancy

33
Q

Tacrolimus side effects

A

Nephrotoxicity
Neurotoxicity
Hypertension
More severe diabetogenic effect than cyclosporine

Does NOT cause gingival hyperplasia or hypertrichosis

34
Q

Azathioprine and mercaptopurine side effects

A

Pancytopenia
Hepatotoxicity
Malignancies
N+V, dose-related diarrhoea
Acute pancreatitis

AVOID allopurinol

35
Q

mTOR inhibitors (sirolimus, everolimus) side effects

A

Pancytopenia
Insulin resistance
Hyperlipidaemia due to inhibition of lipoprotein lipase

NOT nephrotoxic

36
Q

MMF side effects

A

Pancytopenia
Infections
Vomiting and diarrhoea
Hyperglycaemia
HTN

Low neurotoxicity and nephrotoxicity (comparatively)

37
Q

Methotrexate side effects

A

Bone marrow suppression - pancytopenia and/or macrocytic anaemia
Mucositis
Hepatotoxicity
Nephrotoxicity
GI side effects
Diarrhoea

38
Q

Contraindications to anti-TNF-a treatment

A

Pregnancy
Chronic infections, particularly TB
Multiple sclerosis (NEGATIVE effect)
Malignancy (increased lymphoma)
Immunosuppressed
Systemic or localised infections
Mod-severe heart failure

39
Q

Examples of anti-TNF-a treatment

A

Infliximab
Adalimumab
Etanercept

40
Q

MOA of mTOR inhibitors

A

Sirolimus, everolimus

Binds to FK binding protein and modulates activity of mammalian target of rapamycin (mTOR)
mTOR inhibits IL-2 mediated signal transduction resulting in cell cycle arrest in G1-S phase

Also blocks T and B cell activation by cytokines, preventing cell cycle progression and proliferation

41
Q

MOA of calcineurin inhibitors

A

Cyclosporin, tacrolimus

Inhibits calcineurin from dephosphorylating nuclear factor of activated T cells, inhibiting T cell activation

Cyclosporin via cyclophilin binding
Tacrolimus via FKBP12 binding

42
Q

Signals for immunosuppresants which target T cells division

A

Signal 1 - activation via antigen presentation (T cell CD3- and APC MHC)
Signal 2 - co-stimulation, for optimal T cell activation (Signal 1-activated T cell CD28, and APC CD80/86)
Signal 3 - cytokine activation, for T cell proliferation (Signal 2-activated T cell and cytokine, predominantly IL-2)

43
Q

MOA of Abatacept, belatacept

A

Agents which target signal 2
Anti-CD28/CTLA-Ig agent
Competitively bind to CD80/86 and downregulates T cell response

44
Q

MOA of bleselumab

A

AntiCD40mAb agent
Inhibits interaction between activated T cell CD154 (or CD40L) and APC CD40
Leads to upregulation of CD80/86 on APCs and increased T cell co-stimulation

45
Q

MOA of anti-thymocyte globulin

A

Antibodies to human lymphocyte antigens created via immunising rabbits with human thymocytes
Induces lymphocyte depletion via complement dependent lysis and T cell activation-induced apoptosis

46
Q

MOA of azathioprine

A

Purine analogues which interfere with de novo purine synthesis and thus DNA and RNA synthesis
S-G2 cell cycle arrest

47
Q

MOA of mycophenolate

A

Inhibitor of inosine 5 monophosphate dehydrogenase, involved in guanine nucleotide synthesis

48
Q

MOA of leflunomide

A

Inhibits dehydro-orate dehydrogenase inhibiting de novo pyrimidine synthesis and thus DNA synthesis and cell cycling from S to G2

49
Q

MOA of mTOR inhibitors

A

Sirolimus, everolimus

Inhibits lymphocyte cell cycle progression G1 to S phase –> prevents cell proliferation
Also has anti-proliferative, anti-viral, anti-inflammatory, and anti-tumour effects

50
Q

MOA of belimumab

A

BAFF monoclonal antibody
Inhibits binding of BAFF to its B cell receptors

51
Q

MOA of atacicept

A

TACI-Ig
Inhibits binding of cytokine BAFF to B cell receptors
Prevents increase in NH-kB which would otherwise promote B cell differentiation and inhibit apoptosis

52
Q

MOA of bortezomib

A

Proteasome inhibitor
Disrupts regulation of plasma cells

53
Q

IL-1 inhibitors

A

Anakinra, canakinumab
Used in RA, Still’s disease
Inhibits IL-1 and numerous inflammatory effects

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