Immunosuppressants + Flashcards
bDMARDs
Anti TNF alpha: Etanercept Infliximab Adalimumab Golimumab
Immunomodulating: Anakinra Belimumab Abatacept Tocilizimab
Immunosuppressive
Rituximab
csDMARDs
Methotrexate Leflunomide Hydroxychloroquine Azathioprine Sulfasalazine Cyclosporine Cyclophosphamide Mycocephenolate Mofetil
tsDMARD
Tofacitinib
Immunosuppressives
Leflunomide Teriflunomide Corticosteorids: Glucocorticoids Calcineurin and mTOR inh: Cyclosporine, Tacrolimus, Sirolimus, Everolimus, Temsirolimus Tofecitinib Azathioprine Mycocephenolate Mofetil
Teriflunomide - MoA
Same as Leflunomide. Inhibits leukocyte & T-cell proliferation by inhibiting pyrimidine synthesis (DNA replication, RNA synthesis, protein synthesis) in immune cells.
Teriflunomide - Clinical use
Relapsing-remitting multiple sclerosis.
Teriflunomide - Contraindication
Pregnancy and patients with severe liver disease.
Teriflunomide - Adverse effects
Same as Leflunomide
Glucocorticoids - MoA
Biochemical level:, their actions on gene expression decrease the synthesis of prostaglandins, leukotrienes, cytokines, and other signaling molecules that paricipate in immune responses (eg, platelet activating factor).
Cellular level: the glucocorticoids inhibit the proliferation of T lymphocytes and are cytotoxic to certain subsets of T cells
Humoral immunity is also dampened continuous therapy lowers IgG levels by increasing the catabolic rate.
Glucocorticoids - Clinical use
Medical conditions that have an underlying undesirable immunologic basis.
Suppress immunologic reaction in patients undergoing organ-transplant.
Treat hematologic cancers
Glucocorticoids - Adverse effects
Adrenal suppression Growth inhibition Muscle wasting Osteoporosis Salt retention Glucose intolerance Behavioral changes
Calcineurin and mTOR inhibitors - MoA
Interfere with T-cell function by binding to immunophilins.
Calcineurin and mTOR inhibitors - Clinical use
Prevent the increased production of cytokines that normally occurs in response to T-cell receptor activation.
Solid organ transplantation.
Prevent and treat graft-versus-host (GVH) disease (allogeneic stem cell transplantation)
Cyclosporine - MoA
Binds to cyclophilin –> completely inhibits calcineurine
Cyclosporine and Tacrolimus - Clinical use
Some autoimmune diseases:
RA, uveitis, psoriasis, asthma, DIA1
Cyclosporine and Tacrolimus - Adverse effects
Most common: Renal dysfunction, hypertension, neurotoxicity Also: Hyperglycemia, hyperlipidemia, cholelithiasis.
Cyclosporine - Interaction
slow hepatic metabolism by CYT P-450
Tacrolimus - MoA
Binds to FK-binding protein (FKBP) –> completely inhibits calcineurine
Cyclophosphamide - MoA
Cross-links DNA to prevent cell replication. It suppresses T- cell and B-cell.
Cyclophosphamide - Clinical use and Adverse effects
SLE, vasculitis, Wegener’s granulomatosis.
Adverse effects: Large doses: risk of pancytopenia.
May cause hemorrhagic cystitis which can be treated or prevented with mesna.
Sirolimus and analogs - MoA
Binds to FKBP 12. Inhibit the kinase activity of mammalian target of rapamycin (mTOR). By inhibiting the mTOR pathway, inhibits T-cell proliferation response to IL.2
Sirolimus and analogs - Clinical use
Prevent restenosis after coronary angioplasty.
Everolimus: immunosuppressant
Everolimus and temsirolimus: cancers
Sirolimus and analogs - Adverse effects and Contraindication
Hypertriglyceridemia
Hepatotoxicity
Diarrhea
Myelosuppression.
Pregnancy
Tofecitinib (Xeljanz) - MoA
Selectively inhibits all members of the Janus kinase family.
Tofecitinib (Xeljanz) - Clinical use
Adults with moderate to severe RA.
Prevent solid organ allograft rejection.
Inflammatory bowel disease
Mycocephenolate Mofetil - MoA
Rapidly converted into mycophenolic acid, which inhibits inosine monophosphate dehydrogenase (involved in GTP synthesis pathway) –> suppression of B and T-lymphocyte activation.
Mycocephenolate Mofetil - Clinical use
Sole agent in kidney, liver and heart transplantations
Mycocephenolate Mofetil - Special consideration
Renal transplantation: use with low-dose cyclosporine to reduce the cyclosporine-induced nephrotoxicity
Mycocephenolate Mofetil - Adverse effects
GI distrubances
Myelosuppression
Neutropenia
Thalidomide - MoA
Suppression of TNF-α production, increased IL-10, reduced neutrophil phagocytosis, altered adhesion molecule expression, and enhanced cell-mediated immunity.
Inh il-2, angiogenesis, tnf alpha
Thalidomide - Clinical use
Leprosy Immunologic diseases (systemic lupus) Anticancer Aphthous ulcers Wasting syndrome in AIDS patients.
Thalidomide derivatives and their clinical use
Lenalidomide and Pomalidomide
Multiple myeloma
Ustekinumab- MoA
IgG monoclonal antibody. Prevents binding of the p40 subunit of both IL-12 and IL-21
Ustekinumab - Clinical use
IV for Crohn
Adult with PsA
Plaque psoriasis and Crohn`s disease.
Ustekinumab - Adverse effects
Upper respiratory tract infection.
Reversible posterior leukoencephalopathy syndrome.
Secukinumab - MoA
IgG1 monoclonal antibody. Selectively binds to and inhibits IL-17A
Secukinumab - Clinical use
Moderate to severe plaque psoriasis.
Psoriatic arthritis.
Ankylosing spondylosis
Secukinumab - Adverse effects
Infection is a common side effect.
Nasopharyngitis
It may exacerbate Crohn`s disease.
Tofecitinib - Adverse effects and interactions
Metabolized by CYP-450 in the liver. Should be screened for latent or active tuberculosis- Not given to patients with severe hepatic disease.
Increase risk of infection.
Upper respiratory tract infection and urinary tract infection.
Belimumab - MoA
Inhibits B-lymphocyte stimulator (BLyS)
Belimumab - Clinical use
Approved only for the treatment of adult patients with active, seropositive SLE who are receiving standard treatment.
Belimumab - Contraindication
Should not be used in patients with active renal or neurological manifestations of SLE.
Belimumab - Adverse effects
Nausea, diarrhea, and respiratory tract infections.
Increased risk of infections.
Cases of depression and suicide have been reported in patients receiving belimumab, although these patients may have had neurologic SLE.
Anaphylaxis.
Azathioprine - MoA
Acts through its metabolite 6-thioguanine, which suppresses inosinic acid synthesis, B- cell and T-cell function, Ig production, and IL-2 secretion.
Azathioprine - Clinical use
RA
Prevention of kidney transplant rejection in combo with other immune suppressants.
PA, reactive arthritis, polymyositis, SLE, maintenance of remission in vasculitis, and Behcet`s disease.
Scleroderma
Azathioprine - Adverse effects
Bone marrow suppression (low TPMT).
- Increased risk of infection.
- lymphoma risk.
- rarely, fever, rash and hepatotoxicity signal acute allergic reactions.
Rituximab - MoA
Monoclonal antibody that binds to protein CD20 and cause apoptosis. Found on the surface of B cells.
Rituximab - Clinical use
Moderate- severe RA in combo w methotrexate in patients with an inadequate response to one or more TNF-alpha antagonist.
Granulomatosis with polyangiitis (Wegener’s granulomatosis) and microscopic polyangiitis.
Lymphomas and leukemia.
Rituximab - Adverse effects
30% develop rash.
IgG and IgM may decrease.
Serious, and sometimes fatal, bacterial, fungal, and viral infections are reported 1y of last dose.
Associated with reactivation of HBV infection.
Fatal mucocutaneous reactions.
Different cytopenia`s.
