Immunosuppressants +

Question 1

bDMARDs

Answer 1

Anti TNF alpha:
Etanercept
Infliximab
Adalimumab
Golimumab

Immunomodulating:
Anakinra
Belimumab
Abatacept
Tocilizimab

Immunosuppressive
Rituximab

Question 2

csDMARDs

Answer 2

Methotrexate 
Leflunomide 
Hydroxychloroquine
Azathioprine
Sulfasalazine
Cyclosporine 
Cyclophosphamide
Mycocephenolate Mofetil

Question 3

tsDMARD

Answer 3

Tofacitinib

Question 4

Immunosuppressives

Answer 4

Leflunomide
Teriflunomide
Corticosteorids: Glucocorticoids
Calcineurin and mTOR inh: Cyclosporine, Tacrolimus, Sirolimus, Everolimus, Temsirolimus
Tofecitinib
Azathioprine 
Mycocephenolate Mofetil

Question 5

Teriflunomide - MoA

Answer 5

Same as Leflunomide. Inhibits leukocyte & T-cell proliferation by inhibiting pyrimidine synthesis (DNA replication, RNA synthesis, protein synthesis) in immune cells.

Question 6

Teriflunomide - Clinical use

Answer 6

Relapsing-remitting multiple sclerosis.

Question 7

Teriflunomide - Contraindication

Answer 7

Pregnancy and patients with severe liver disease.

Question 8

Teriflunomide - Adverse effects

Answer 8

Same as Leflunomide

Question 9

Glucocorticoids - MoA

Answer 9

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.

Question 10

Glucocorticoids - Clinical use

Answer 10

Medical conditions that have an underlying undesirable immunologic basis.
Suppress immunologic reaction in patients undergoing organ-transplant.
Treat hematologic cancers

Question 11

Glucocorticoids - Adverse effects

Answer 11

Adrenal suppression
Growth inhibition
Muscle wasting
Osteoporosis
Salt retention
Glucose intolerance
Behavioral changes

Question 12

Calcineurin and mTOR inhibitors - MoA

Answer 12

Interfere with T-cell function by binding to immunophilins.

Question 13

Calcineurin and mTOR inhibitors - Clinical use

Answer 13

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)

Question 14

Cyclosporine - MoA

Answer 14

Binds to cyclophilin –> completely inhibits calcineurine

Question 15

Cyclosporine and Tacrolimus - Clinical use

Answer 15

Some autoimmune diseases:

RA, uveitis, psoriasis, asthma, DIA1

Question 16

Cyclosporine and Tacrolimus - Adverse effects

Answer 16

Most common:
Renal dysfunction, hypertension,
neurotoxicity 
Also:
Hyperglycemia, hyperlipidemia, cholelithiasis.

Question 17

Cyclosporine - Interaction

Answer 17

slow hepatic metabolism by CYT P-450

Question 18

Tacrolimus - MoA

Answer 18

Binds to FK-binding protein (FKBP) –> completely inhibits calcineurine

Question 19

Cyclophosphamide - MoA

Answer 19

Cross-links DNA to prevent cell replication. It suppresses T- cell and B-cell.

Question 20

Cyclophosphamide - Clinical use and Adverse effects

Answer 20

SLE, vasculitis, Wegener’s granulomatosis.

Adverse effects: Large doses: risk of pancytopenia.
May cause hemorrhagic cystitis which can be treated or prevented with mesna.

Question 21

Sirolimus and analogs - MoA

Answer 21

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

Question 22

Sirolimus and analogs - Clinical use

Answer 22

Prevent restenosis after coronary angioplasty.

Everolimus: immunosuppressant
Everolimus and temsirolimus: cancers

Question 23

Sirolimus and analogs - Adverse effects and Contraindication

Answer 23

Hypertriglyceridemia
Hepatotoxicity
Diarrhea
Myelosuppression.

Pregnancy

Question 24

Tofecitinib (Xeljanz) - MoA

Answer 24

Selectively inhibits all members of the Janus kinase family.

Question 25

Tofecitinib (Xeljanz) - Clinical use

Answer 25

Adults with moderate to severe RA. Prevent solid organ allograft rejection. Inflammatory bowel disease

Question 26

Mycocephenolate Mofetil - MoA

Answer 26

Rapidly converted into mycophenolic acid, which inhibits inosine monophosphate dehydrogenase (involved in GTP synthesis pathway) --> suppression of B and T-lymphocyte activation.

Question 27

Mycocephenolate Mofetil - Clinical use

Answer 27

Sole agent in kidney, liver and heart transplantations

Question 28

Mycocephenolate Mofetil - Special consideration

Answer 28

Renal transplantation: use with low-dose cyclosporine to reduce the cyclosporine-induced nephrotoxicity

Question 29

Mycocephenolate Mofetil - Adverse effects

Answer 29

GI distrubances Myelosuppression Neutropenia

Question 30

Thalidomide - MoA

Answer 30

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

Question 31

Thalidomide - Clinical use

Answer 31

``` Leprosy Immunologic diseases (systemic lupus) Anticancer Aphthous ulcers Wasting syndrome in AIDS patients. ```

Question 32

Thalidomide derivatives and their clinical use

Answer 32

Lenalidomide and Pomalidomide | Multiple myeloma

Question 33

Ustekinumab- MoA

Answer 33

IgG monoclonal antibody. Prevents binding of the p40 subunit of both IL-12 and IL-21

Question 34

Ustekinumab - Clinical use

Answer 34

IV for Crohn Adult with PsA Plaque psoriasis and Crohn`s disease.

Question 35

Ustekinumab - Adverse effects

Answer 35

Upper respiratory tract infection. Reversible posterior leukoencephalopathy syndrome.

Question 36

Secukinumab - MoA

Answer 36

IgG1 monoclonal antibody. Selectively binds to and inhibits IL-17A

Question 37

Secukinumab - Clinical use

Answer 37

Moderate to severe plaque psoriasis. Psoriatic arthritis. Ankylosing spondylosis

Question 38

Secukinumab - Adverse effects

Answer 38

Infection is a common side effect. Nasopharyngitis It may exacerbate Crohn`s disease.

Question 39

Tofecitinib - Adverse effects and interactions

Answer 39

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.

Question 40

Belimumab - MoA

Answer 40

Inhibits B-lymphocyte stimulator (BLyS)

Question 41

Belimumab - Clinical use

Answer 41

Approved only for the treatment of adult patients with active, seropositive SLE who are receiving standard treatment.

Question 42

Belimumab - Contraindication

Answer 42

Should not be used in patients with active renal or neurological manifestations of SLE.

Question 43

Belimumab - Adverse effects

Answer 43

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.

Question 44

Azathioprine - MoA

Answer 44

Acts through its metabolite 6-thioguanine, which suppresses inosinic acid synthesis, B- cell and T-cell function, Ig production, and IL-2 secretion.

Question 45

Azathioprine - Clinical use

Answer 45

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

Question 46

Azathioprine - Adverse effects

Answer 46

Bone marrow suppression (low TPMT). - Increased risk of infection. - lymphoma risk. - rarely, fever, rash and hepatotoxicity signal acute allergic reactions.

Question 47

Rituximab - MoA

Answer 47

Monoclonal antibody that binds to protein CD20 and cause apoptosis. Found on the surface of B cells.

Question 48

Rituximab - Clinical use

Answer 48

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.

Question 49

Rituximab - Adverse effects

Answer 49

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.