B.28 Flashcards
Immunopharmacology III
Blocking T cell surface molecules involved in signaling of immunoglobulins: ATG (antithymocyte-globulin)
Antibodies against B cells: Rituximab
Antibodies against adhesion molecules/cytokines:
- Anti TNFα: Infliximab, Adalimumab
- Anti-IL-1β: Canakinumab
- Anti-IL6R: Tocilizumab
- Anti-IL-17: Secukinumab
- Anti-IL-23: Ustekinumab
- Anti-α4-integrin: Natalizumab
- Anti-IL-13R: Dupilumab
- CTLA4 activator: Abatacept
ATG (antithymocyte-globulin), ALG (Anti-lymphocyte-globulin)
MOA: They are isolated from blood of rabbits or horses immunized by human lymphocytes or thymocytes→ it kills and blocks the lymphocytes/thymocytes in the body;
IND: most effective agents against acute graft rejection after transplantation (used if possibility of rejection is high), in BM transplantation the pretreatment of the graft by ALG reduces the GVH disease;
SEs: Dyspnea, Serum disease / anaphylaxis, fever, GI disturbances
Rituximab, Ocrelizumab
MOA: Bind CD20 on both normal and malignant B-cells → reduce B-cell count for several months (after 1 treatment they reduce it dramatically) through complement and cell (macrophages, neutrophil and NK)-mediated pathway. They are also able to induce apoptosis;
IND: Rituximab was developed for malignant B-cell lymphomas and CLL, in RA it’s given periodically (2 doses in 2 weeks and after 6 months of break), it’s also registered for vasculitis diseases, Wegener’s granulomatosis, microscopic polyanfiitis, off lable-therapy resistant autoimmune diseases and organ transplantation, Ocrelizumab can be used for MS;
SEs: infusion-reactions (steroid, paracetamol and antihistamines prophylaxis are needed), Neutropenia (→infections, fever, can be countered with G-CSF Filgrastim), GI disturbances, Hypotension
Infliximab, Adalimumab
MOA: Infliximab- Chimeric Anti-TNFα Ab, Adalimumab-Human Anti-TNFα Ab;
Kinetics: Infliximab- i.v once in 2 months, Biosimilars are available. Adalimumab- s.c. adm once/2weeks;
IND: RA (mostly in comb. with MTX), JIA, Bechterew’s disease (ankylosing spondylitis), Psoriasis, IBDs;
SEs: risk of infections (TB, opportunistic infections, activation of latent viral hepatitis), injection sites and infusion reactions, allergy;
Extra: Neutralizing Ab formation is possible (more common with infliximab)
Tocilizumab
MOA: Anti-IL-6R Ab (→block the receptor, not the cytokine itself!);
IND: RA, JIA;
Kinetics: monthly i.v.;
SEs: neutropenia, increased lipid level,risk of infections (TB, opportunistic infections, activation of latent viral hepatitis), injection sites and infusion reactions, allergy
Ustekinumab
MOA: Anti-IL-12/13 Ab (→ it binds to the common p40 subunit of IL-12 and IL-23 →preventing the activation of the proinflammatory lymphocytes TH1 cells and TH17 cells respectively);
IND: Psoriasis (plaqe psoriasis, arthritis psoriatica), Crohn’s disease;
SEs: infections
Natalizumab
MOA: it inhibits the docking and extravasation of T-cells through α4β1-VCAM-1 interaction in CNS and α4β7-MadCAM-1 in GIT;
IND: multiple sclerosis;
SEs: Fever, Nausea, Infections, Progressive multifocal leukoencephalopathia (it can activate with a 1:1000 possibility polyomavirus JC→leading to PML)
Dupilumab
MOA: Anti-IL-4αR and IL-13R Ab (→it blocks also TH2 mediated immunreaction);
IND: Eosinophilic asthma, atopic dermatitis;
SEs: Local reactions, Oral herpes, Conjunctivitis, Ab formation
Abatacept
MOA: It blocks the interaction of the co-stimulator CD28 with CD80/86 by binding to CD80/86 (CD80/86 - CTLA4 interaction is inhibitory on lymphocytes);
IND: RA, JIA (with uveitis), Psoriatic arthritis;
SEs: Headache, Infections, (neutralizing) Ab production
Biosimilar
Biopharmaceutical drus designed to have active properties similar to those of a drug that has previously been licensed
Neutralizing antibody
type of Ab that can specifically recognize and bind to a virus or other pathogen, preventing it from infecting cells or causing disease. They neutralize the biological activity of the pathogen, often by blocking its entry into a cells or preventing it from replicating. Neutralizing Abs are produced by the immune system in response to exposure to a pathogen or through vaccination.
PML
Progressive myeloid leukoencephalopathy→ a demyelinating disease of the CNS
Main groups of immunosuppressive drugs
- Cytotoxic agents
- Inhibitors of cytokine production or action
- Inhibitors of cytokine gene expression
- Immunosuppressive Abs:
- Blocking T cell surface molecules involved in signaling of imuunoglobulins
- Antibodies against T cells
- Antibodies against B cells
- Antibodies against adhesion molecules/cytokines::4 groups - Non-specific immunosuppresants
- Interferons
- Immunostimulants
Nomenclature of Antibodies
Mouse: -omab (e.g. Muromab)
Chimera: -ximab (e.g. Infliximab)
Humanized: -zumab (e.g. Palivizumab)
Human: -mumab (e.g. Panitumumab)
- Other non-specific immunosuppressants:
Cloroquine, Hydroxychloroquine
MOA: ↑lysosomal pH in macrophages (→inhibiting the presentation of antigens), block autophagy and formation of proinflammatory mediators;
Kinetics: good absorption, T1/2 up to 40 days, hepatic metabolism;
IND: RA (in combo or monotherapy in mild cases), SLE, DLE, Sjorgen’s syndrome;
SEs: skin exanthemas, stomachache, nausea, vomiting, myopathy, nightmares, maculadegeneration and cornea discoloration
