Immunomodulatory Drugs Flashcards
Immune boosting methods
Vaccination
Replacement of missing components e.g transplantation of bone marrow
Immunoglobulin (subcutaneous or IV)
T cell infusion used in Ebv or CMV particularly
Cytokines infusion eg interferon alpha
Interferon alpha uses
Hepatitis C
Hepatitis b
Kaposis hhv8
Name 4 anti T cell monoclonal antibodies
BMAT
Baciliximab
Muromonab
Abatacept
Tocilizumab
Name 3 anti proliferative agents
Cyclophosphamide
Mycophenylate
Azothioprine
Name 3 immune boosting monoclonal antibodies
Ipilimumab
Pembrolizumab
Nivolumab
What is the mode of action for ipilimumab
Antibody against CTLA4 blocking immune checkpoint.
Allows CD80 and CD86 to bind to CD28 and activate T cells.
What is the mode of action for pembrolizumab
PD1 blockade.
Would otherwise be stimulated by Treg cells dampening down the immune response.
This allows activation of T cells more readily.
Name a monoclonal antibody used for advanced melanoma. What are its side effects?
PD1 antibodies
Pembrolizumab
Nivolumab
Causes IBD and inflammatory joint disease
1 use for interferon gamma
Chronic granulomatous disease
Human immunoglobulin use
Hyper IGM (x linked)
CorticoSteroid mode of action for immunosuppression 6 ways
Inhibit phospholipase a2 to reduce arachidonic acid and therefore prostaglandin production via cyclooxygenases
Also blocks transendothelial migration of phagocytes by reducing expression of adhesion molecules.
Causes a slightly raised neutrophil count
Inhibit release of proteolytic enzymes in phagocytes.
Lymphocytes remain in lymphoid tissue causing a lymphopenia
Blocks cytokines expression
Decreased antibody production
Promotes apoptosis
Use and Side effects of cyclophosphamide
Anca associated vasculitis
Renal lupus
Bone marrow suppression
Hair loss and sterility
Haemorrhagic cystitis (acrolein)
Malignancy Bladder blood (basal cell carcinomas) or non melanoma skin ca
PCP infection
Azothioprine uses and mode of action
IBD
Lupus
Anti proliferative
Converted to 6 mercaptopurine which inhibits DNA synthesis by blocking purine synthesis.
Acts primarily on T cells by inhibiting activation and replication
Mycophenolate mofetil mode of action
Blocks de novo synthesis of nucleotides and prevents T cell replication (more than B cell)
Used in transplantation
Autoimmune disease and vasculitis.
Side effects of Azothioprine
1 in 300 people are susceptible to bone marrow suppression due to Azothioprine build up with a lack of metabolism. This is due to genetic polymorphisms in thiopurine methyltransferase
Must check tpmt activity
Infection
Side effects of mycophenylate mofetil
Progressive multifocal leukoencephalopathy. Due to JC virus reactivation.
CMV Reactivation
Bone marrow suppression. Infection
Uses for plasmapheresis
Severe Anti GBM
Severe acute myasthenia Gravis
Severe vascular rejection
(Mostly type 2 mediated hypersensitivity)
Name 4 cell signalling inhibitors
Cyclosporin
Tacrolimus
Apremilast
Tofacitinib
Tofacitinib use and mechanism
RA
JAK inhibitor
Apremilast use and mechanism
Psoriasis and psoriatic arthritis
PDE4 inhibitor
Cyclosporine side effects
Hypertension Gum hypertrophy and hirsuitism Nephrotoxicity. Neurotoxicity Diabetogenic
Low doses can be used in pregnancy eg lupus
Psoriasis
Cyclosporin and tacrolimus mode of action.
Calcineurin
IL2 production inhibited preventing activation and proliferation of T cells.
Tacrolimus side effects
Diabetogenic
Hypertension
Nephrotoxic
Neurotoxic
Rabbit anti thymocyte globulin
Human thymocyte placed into rabbit
Antibodies formed in serum against human T cells.
Can cause leukopenia and transfusion reactions and infection
Malignancy
Baciliximab
Used to prevent graft rejection
Cd25 blocker. Blocking IL2 activation and proliferation of T cells.
Abatercept
Ctla4 with IG. Blocks cd80 and cd86
Cannot activate cd28 or ctla4 and therefore doesn’t activate T cells
Works in RA
Rituximab
Cd20 antibody. Binds to mature B cells but leaves plasma cells so have protective immunity still.
Used in lymphoma, rheumatoid, lupus. 2 doses per year
SE
Progressive multifocal leukoencephalopathy
Infusion reactions
Worsens CVD
Natalizumab
Alpha 4 integrin
Bonds to VCAM1 and MadCAM1 to prevent rolling and transendothelial migration of leukocyte so.
Highly active relapsing remitting MS
Every4 weeks IV
PML
infusion reactions
Efalizumab
Cd11a to inhibit T cell migration
Was used for psoriasis
Withdrawn due to PML
Tocilizumab
IL6recepter monoclonal antibody
Can bind to soluble or anchored form in gp130
Reduces macrophage, T cell, B cell, neutrophil activation. V potent.
Rheumatoid arthritis
Castlemans (lymphoproliferative disorder)
Can cause severe depression resulting in infections
Tocilizumab Indications
RA
Name 5 anti TNF alpha drugs
CAGI E
certolizumab
Adalimumab
Golimumab
Infliximab
Ertanercept
Uses of anti TNF alpha
RA Ank spond Psorriasis Psoriatic arthritis IBD
IV or subcutaneous (except infliximab)
Side effects of anti TNF alpha
Injection site reactions TB AND HEPATITIS Lupus like skin Demyelination Skin malignancy
What is etanercept not useful in
IBD
What is ustekinumab
Binds to p40 subunit of il12/23
Inadvertently stops activation of th17 and therefore il17 expression.
Used in psoriasis and psoriatic arthritis
Subcut every 12 weeks
What is secukinumab
Il17 family (alpha) mab
Used in psoriasis and psoriatic arthritis.
Also for use in ankylosis get spondylitis
What is denosumab
RANK-L mab
Second line treatment in osteoporosis
After alendronate
Inhibits rank mediated osteoclast differentiation and function
Chronic infection is a problem with biologics. Which infections are they t risk of
TB
HEP B (check core antibody)
hepc
Risk of Immunosuppression
Lymphoma
Skin cancer
Autoimmunity
side effects of methotrexate?
pulmonary fibrosis, pneumonitis and liver cirrhosis
muromonab
CD3 blocker
for active rejection which is corticosteroid resistant
