Immunomodulators Flashcards
Pembrolizumab MOA
Humanised PD-1 inhibitor
Examples of PD-L1 inhibitors
Durvalumab
Atezolimumab
Specific side effects of PD-1 and PD-L1 inhibitors
Increased risk of autoimmune conditions i.e. pneumonitis, dermatitis
Alemtuzumab MOA
CD52 inhibitor - used for MS and CLL
Presents on B and T cells - depletes both lymphoid cell lines
Alemtuzumab side effects
Autoimmune conditions i.e. autoimmune thyroiditis, ITP
Examples of anti-TNF alpha agents
Chimeric - Infliximab
Humanised - Adalimumab, Golimumab, certolizumab
Indications for anti-TNA-alpha
Refractory therapy for chronic inflammatory systemic diseases
- RA
- Ankylosing spondylitis
- Psoriasis, PA
- CD, UC
Side effects of TNA-a inhibitors
Severe infections
Reactivation of prior infections
Drug-induced lupus
MOA and side effects of etanercept
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
MOA and side effects of rituximab
Chimeric CD20 inhibitor
Reactivation of JC virus infection –> PML
Infusion reaction
Rituximab uses
RA
ITP
TTP
MS
AIHA
NHL
Symptomatic Waldenstrom macroglobulinaemia
MOA, use and S/E of natalizumab
Humanised alpha-4-integrin inhibitor
Escalation therapy of MS
Crohn’s disease
Reactivation of latent JC virus
Infusion reactions
MOA and uses of cetuximab
Chimeric EGFR inhibitor
Used for
CRC stage IV, wide type KRAS
Head and neck cancer
MOA and uses of panitumumab
Humanised EGFR inhibitor
Used for
CRC stage IV, wide type KRAS
Head and neck cancer
MOA of tocilizumab
Humanised IL-6 inhibitor
Used for
GCA
Juvenile idiopathic arthritis
RA
Severe COVID-19
MOA of secukinumab
Human IL-17A inhibitor
Decreases inflammatory cell migration, B cell differentiation and activation of hepatic acute phase response
Used for
Psoriasis
Psoriatic arthritis
MOA of ixekizumab
Humanised IL-17A inhibitor
Used for psoriasis
Psoriatic arthritis
MOA of brodalumab
Human IL-17R inhibitor
Used for treatment-refractory psoriasis
MOA of vedolizumab
Humanised a4B7 integrin inhibitor
Used for
CD
UC
MOA of ustekinumab
Human IL12/23 inhibitor
Used for
Psoriasis, PsA
Crohn’s
MOA of omalizumab
Humanised
Acts on unbound serum IgE
Severe persistent allergic asthma (resistant to inhaled steroids and LABAs) with increased IgE
SE of omalizumab
Arthralgia
Fatigue, dizziness
Pruritus, dermatitis
MOA, use and side effects of abciximab
Chimeric antagonist of GPIIb/IIIa receptors
Antiplatelet agent, used for patients undergoing PCI
Causes acute thrombocytopenia, haemorrhage
Muromonab MOA, use and side effects
Anti-CD3 (from T cells)
Used for steroid-resistant acute rejection post-transplantation
Causes cytokine storm
Basiliximab MOA, use and side effects
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
Daclizumab MOA
Humanised anti-CD25
Similar use and side effect profile to basiliximab (MS, causes tremor, HTN and oedema)
Trastuzumab MOA, use and side effects
Humanised HER2/neu tyrosine kinase receptor
Inhibits HER2-initiated cellular signalling and antibody-dependent cytotoxicity
Causes dilated cardiomyopathy
Bevacizumab MOA, uses and side effects
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
Eculizumab MOA, uses and side effects
Humanised complement protein C5 inhibitor
Used in PNH and HUS
Increased risk of infection with encapsulated bacteria e.g. N meningitidis
Ipilimumab MOA, uses and side effects
Human CTLA-4 inhibitor
Melanoma, lymphoma, lung cancer, RCC, urothelial carcinoma, prostate cancer
Increased risk of autoimmune conditions
Guselkumab MOA and uses
Human IL-23 inhibitor
Used for psoriasis
Increased risk of autoimmune conditions
Examples of PD-1 inhibitor and uses
Pembrolizumab
Nivolumab
Cemiplimab
RCC, urothelial carcinoma, nSCLC, Melanoma
Cyclosporine side effects
Nephrotoxicity
Gingival hyperplasia
Hypertrichosis and hirsutism
Diabetogenic effect - hyperuricaemia, hyperlipidaemia, elevated liver enzymes
Increase in malignancy
Tacrolimus side effects
Nephrotoxicity
Neurotoxicity
Hypertension
More severe diabetogenic effect than cyclosporine
Does NOT cause gingival hyperplasia or hypertrichosis
Azathioprine and mercaptopurine side effects
Pancytopenia
Hepatotoxicity
Malignancies
N+V, dose-related diarrhoea
Acute pancreatitis
AVOID allopurinol
mTOR inhibitors (sirolimus, everolimus) side effects
Pancytopenia
Insulin resistance
Hyperlipidaemia due to inhibition of lipoprotein lipase
NOT nephrotoxic
MMF side effects
Pancytopenia
Infections
Vomiting and diarrhoea
Hyperglycaemia
HTN
Low neurotoxicity and nephrotoxicity (comparatively)
Methotrexate side effects
Bone marrow suppression - pancytopenia and/or macrocytic anaemia
Mucositis
Hepatotoxicity
Nephrotoxicity
GI side effects
Diarrhoea
Contraindications to anti-TNF-a treatment
Pregnancy
Chronic infections, particularly TB
Multiple sclerosis (NEGATIVE effect)
Malignancy (increased lymphoma)
Immunosuppressed
Systemic or localised infections
Mod-severe heart failure
Examples of anti-TNF-a treatment
Infliximab
Adalimumab
Etanercept
MOA of mTOR inhibitors
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
MOA of calcineurin inhibitors
Cyclosporin, tacrolimus
Inhibits calcineurin from dephosphorylating nuclear factor of activated T cells, inhibiting T cell activation
Cyclosporin via cyclophilin binding
Tacrolimus via FKBP12 binding
Signals for immunosuppresants which target T cells division
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)
MOA of Abatacept, belatacept
Agents which target signal 2
Anti-CD28/CTLA-Ig agent
Competitively bind to CD80/86 and downregulates T cell response
MOA of bleselumab
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
MOA of anti-thymocyte globulin
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
MOA of azathioprine
Purine analogues which interfere with de novo purine synthesis and thus DNA and RNA synthesis
S-G2 cell cycle arrest
MOA of mycophenolate
Inhibitor of inosine 5 monophosphate dehydrogenase, involved in guanine nucleotide synthesis
MOA of leflunomide
Inhibits dehydro-orate dehydrogenase inhibiting de novo pyrimidine synthesis and thus DNA synthesis and cell cycling from S to G2
MOA of mTOR inhibitors
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
MOA of belimumab
BAFF monoclonal antibody
Inhibits binding of BAFF to its B cell receptors
MOA of atacicept
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
MOA of bortezomib
Proteasome inhibitor
Disrupts regulation of plasma cells
IL-1 inhibitors
Anakinra, canakinumab
Used in RA, Still’s disease
Inhibits IL-1 and numerous inflammatory effects
