Anti-inflammatory and Immune drugs Flashcards
Immunostimulant
Given to boost immunity
Recombinant cytokines
Immunosuppressant
Given to treat inflammatory diseases
Atopy, autoimmune disease, prevent transplant rejection
What can alpha-IFN be used to treat?
Warts from papilloma and Kapsoi’s sarcoma
What can beta-IFN be used to treat?
Therapy for Multiple sclerosis
What can gamma-IFN be used for?
Boost phagocyte NADPH oxidase system in pts with chronic granulomatous disease
What agents stimulate leukocyte production from bone marrow?
Recombinant G-CSF, GM-CSF
Pts with secondary neutropenia secondary to chemotherapy
What are the steps in inflammation?
Activation of innate immune cells
Release of inflammatory mediators
B and T cells become activated
What types of drugs interfere with arachidonic acid metabolites?
Non-steroidal anti-inflam (NSAIDS)
Leukotriene inhibitors
Corticosteroids
What types of drugs interfere with cytokines?
Corticosteroids Cytokine inhibitors (monoclonal antibodies)
What drugs are used to inhibit T and B cell responses?
Corticosteroids Cytotoxic drugs Cyclosporine Cytokine inhibitor Biological inhibitors of lymphocyte activation/inducers of apoptosis
What drug blocks phopholipases?
Steroid inhibit (corticosteroid)
What drug blocks cyclooxygenase?
Non-steroidal inhibitors
What are leukotriene inhibitors used for?
Mild or moderate asthma since leukotrienes cause bronchoconstriction and eosinophil attraction
Which leukotriene inhibitor inhibitors lipoxygenase?
Zileuton
Which leukotriene inhibitors are receptor antagonists?
Zafirlukast
Montelukast
What is the mechanism of action for corticosteroids?
GSC enters cell binds to GCSR
Complex binds to DNA
Up regulates lipocortins which block AA metabolism
Inhibits transcription of cytokine genes by blocking NFKB and up-regulating transcription factor inhibitors
Glococorticoids block the action of ______ inhibiting the formation of ______.
Phospholipase A2, Free arachidonic acid
What is the action of Cytotoxic drugs?
Kill rapidly dividing cells
Lymphocyte proliferation in clonal expansion, bone marrow cells
What are cytotoxic used for treatment of?
Autoimmunity or to prevent grapft rejection
What drugs are cytotoxic?
Azathiprine (purine analogue - nucleic acid synth)
Cyclophosphamide (Alkylating agent - DNA binding)
Methotrexate (Folic acid antagonist - DNA + RNA)
What drugs inhibit cytokine secretion and T cell proliferation?
Cyclosporine and Tacrolimus
What were cyclosporin and tacrolimus used for?
Prevent transplant rejection and now used for moderate to severe psoriasis
How do cyclosporin and tacrolimus work?
T cell activation leads to an influx of Ca++ and in combination with calmodulin they bind to calcinerin which activates NFAT to transcribe IL-2 and other
The drugs block calcineurin from activating NFAT
What are the biologicals?
Monoclonal antibodies against cytokines or cytokine receptors
Small molecule inhibitors of cytokine signaling
Murine monoclonal antibody
Entire antibody of mouse origin
Recognized as foreign in human
No long-term treatment use
Chimeric monoclonal antibody
Monoclonal antibody that has human Fc mouse Fab
Have -ximab in name
Humanized monoclonal antibody
Parts of Fab are human
Have -umab in name
Human monoclonal antobody
Entire molecule is human
What are anti-TNF drugs used for?
Rheumatoid arthritis, psoriasis and Chron’s disease
What is the anti-TNF drug which uses chimeric monoclonal antibodies?
Infliximab (Remicade)
Which anti-TNF drug uses chimeric monoclonal antibodies?
Adalimumab (Humira)
Which anti-TNF drug uses recombinant TNF receptors fused to immunoglobulin?
Etanercept
What is Etanercept?
Human soluble TNF receptor fused to the Fc segment of human IgG
How does Ustekinumab work?
The ustekinumab binds to the p40 which is bound to either p35 or p19
It is kept from binding with the IL-12 (p35), IL-23 (p19)
What interleukin does Tocilizumab go after?
IL-6
What does IL-6 do?
Activates T and B cells, macrophages, chronodrocytes and synovial fibroblasts, and osteoclasts
What is Anakinra?
Recombinant IL-1 receptor antagonist
Which disease does IL-1 play a role in?
Rheumatoid arthritis pathogenesis
How does Toficitinib (Xeljanz) work and what is it used for?
Inhibits JAK kinases which is involved for cytokine signaling
Rheumatoid arthritis
Which drug blocks T cell activation?
Abatacept - used for Rheumatoid Arthritis
Which drug inhibits LFA-3/CD2 interaction, thus inhibits T lymphocyte activation?
Alefacept
Which drug causes the death of the B cell upon binding?
Rituximab
What type of hypersensitivity is asthma and explain how it works.
Type 1
Inflammation in bronchial walls
What drugs are used for asthma?
Bronchodilators
Leukotriene inhibitors
Corticosteroids
Explain psoriasis
T-cell induced proliferation of keratinocytes leading to unsightly plaques of red, raised, rough areas of skin
What are the drug used to treat psoriasis?
Methotrexate
Corticosteroids
Cytokine inhibitors
Biologicals
Explain rheumatoid arthritis
T-cell mediated inflammation of joints with resoprtion of bone and joint deformity
What drugs are used to treat rheumatoid arthritis?
Nonsteroidal anti-inflammatory drugs (NSAIDS)
Cytotoxic drugs (methotrexate)
Cytokine inhibitors and other biologicals (anti-TNF, rituximab)
Corticosteroids
What are the key cells and cytokines involved in the pathogenesis of rheumatoid arthritis?
T cells B cells Macrophages Neutrophils TNF IL-1 IL-6
What are the key cells and cytokines involved int he pathogenesis of psoriasis?
Th1 Th17 TNF IL-1 IL-23 IL-12
