Targets and Treatments Flashcards
Describe the adaptive and the innate immune system
-Adaptive= immune responses are tailored (and finely tuned) to pathogens, B lymphocyte, T lymphocyte, APC
-Innate= detect microbial components with non-specific killing of pathogens, neutrophil, NKC etc
-Inflammatory cytokines link
Describe the Human Leukocyte Antigen System
-Antigens are presented to T-cells
bound to HLA class I or HLA class II
molecules
=All cells express HLA I
=Immune cells express HLA II
-T-cells require B7-CD28 for full
activation (co-stimulation)
-Autoimmunity arises when altered
host or foreign peptide is presented
to T-cells in context of disease associated HLA variants
Cellular interactions and therapeutic targets in RA
-Cytokines
=TNF
=IL-6
-T-cells
-B-cells
-Signalling molecules
=JAK
-Prostaglandins
Cellular interactions and therapeutic targets in PsA
-Cytokines
=IL-23
=IL-17
=TNF
-T-cells
-Prostaglandins
Cellular interactions and therapeutic
targets in AxSpA
-Cytokines
=IL-23
=IL-17
=TNF
-Prostaglandins
General symptomatic treatment approaches
-Paracetamol
-NSAID
=Ibuprofen, Naproxen
=Celecoxib, Etoricoxib
-Analgesics
=Codeine, tramadol
-Anti-neuropathic drugs
=Amitriptylene, gabapentinoids
General disease modifying treatment approaches
-cDMARD
=Methotrexate
=Sulfasalazine
=Hydroxychloroquine
=Leflunomide
-Biologics
-tsDMARD
-Steroids
Describe NSAIDs
-Effective treatment for pain
with inflammatory component
-Non-selective
=ibuprofen, naproxen
-COX-2 selective
=Celecoxib, etoricoxib
-Adverse effects
=Cardiovascular disease
=Renal impairment
=GI ulceration (less with COX2)
=Caution in older people
Describe Glucocorticoids
-Powerful anti-inflammatory
effects, rapid onset of action
-Used in many inflammatory
diseases
-Long-term adverse effects
=Osteoporosis
=Infection
=GI ulceration (with NSAID)
=Weight gain, diabetes
=Hypertension
Classical DMARD examples and consequences
Inhibitors of DNA synthesis
=Methotrexate, Azathioprine
=Leflunomide, Mycophenylate,
=Cyclophosphamide
-Inhibit division of immune cells
Inhibitors of Calcineurin
=Ciclosporin
-Inhibit activation of T-cells
Inhibit lysosomes
=Hydroxychloroquine
-Inhibit various signalling pathways in various cells
Unclear
=Sulfasalazine
-Inhibit NFkB and other signalling pathways
Types of targeted immunosuppressive therapies
-Monoclonal antibodies
=Cytokines or cytokine receptors
=Cell surface molecules
-Decoy receptors
=Bind to cytokine preventing receptor activation
-Signalling pathway inhibitors
=Small molecules that target intracellular pathways
Examples of Tumour Necrosis Factor inhibitors
-Indicated in RA, PsA, AxSpA
-Monoclonal antibodies (Mab)
=Infliximab (murine)
=Adalimumab
=Certolizumab
=Golimumab
-Mab binds TNF and neutralises cytokine
-Decoy receptor
=Etanercept: prevents TNF binding to its receptor
Examples of Interleukin-6 pathway inhibitors
Target IL-6 receptors= soluble and membrane bound
-Tocilizumab
=Licensed for RA and GCA
-Sarilumab
=Licensed for RA
Examples of Interleukin-1 pathway inhibitors
-Indicated for Still’s disease and
familial fever syndromes
-Also licensed for acute gout
-Canakinumab
=Monoclonal antibody against IL-1b
-Anakinra
=Decoy receptor for IL-1
Examples of Interleukin-17 and IL-23 inhibitors
-Indicated for Psoriatic Arthritis
and Axial Spondyloarthritis
-IL-23 pathway (macrophage to Th17)
=Ustekinumab (anti-p40)
=Guselkumab (anti-p19)
-IL-17 pathway
=Secukinumab
=Ixekizumab
