Immunosuppressive therapies

Question 1

Corticosteroids e.g. prednisolone

Answer 1

Inhibits phospholipase A2 hence blocks arachidonic acid, reduces prostaglandin synthesis.
Inhibits phagocyte trafficking, phagocytosis and release of proteolytic enzymes.
Decreased Ab production

SEs: neutrophilia, diabetes, central obesity, adrenal supression, cataracts, glaucoma, pancreatitis, osteoporosis, moon face, acne, hirtuism, hypertension, dyslipidaemia, peptic ulceration, avascular necrosis

Question 2

Cyclophosphamide

Answer 2

ANTIPROLIFERATIVE - inhibit DNA synthesis, cells with rapid turnover most sensitive
Alkylates guanine base of DNA, Damages DNA and prevents cell replication, Affects B cells > T cells, but at high doses affects all cells with high turnover

SEs: BM supression, infection, malignancy, teratogenic, hair loss, sterility, haemorrhagic cystitis

Question 3

Mycophenolate Mofetil

Transplantation medication

Answer 3

ANTIPROLIFERATIVE
Inhibits IM PDH, prevents guanine synthesis.
Blocks de novo nucleotide synthesis – prevents replication of DNA, Prevents T>B cell proliferation

SEs: BM suppression, infection/reactivation of viruses, malignancy, teratogenic

Question 4

Azathioprine

Answer 4

ANTIPROLIFERATIVE
Antimetabolite agent Metabolised by liver to 6 mercaptopurine, blocks de novo purine (eg adenine, guanine) synthesis – prevents replication of DNA, preferentially inhibits T cell activation & proliferation

SEs: BM supression, infection, malignancy, teratogenic, hepatotoxicity, neutropenia

TPMT polymorphism - unable to metabolise azathioprine

Question 5

Methotrexate

Answer 5

ANTIPROLIFERATIVE
Inhibits dihydrofolate reductase (DHFR) therefore decreases DNA synthesis

SEs: Bone marrow supression, infection, malignancy, teratogenic, pneumonitis, pulmonary fibrosis, hepatotoxicity, folate deficiency (macrocytic megaloblastic anaemia)

Question 6

Tacrolimus and cyclosporin

Answer 6

INHIBITORS OF CELL SIGNALLING
Inhibits calcineurin which normally activates transcription of IL2, hence reduces T cell proliferation

SEs:
Nephrotoxic, hypertension, neurotoxic

Question 7

Other inhibitors of cell signalling

Answer 7

Sirolimus - blocks clonal proliferation of T cells
Tofacitinib - JAK inhibitor
Apremilast - PDE4 inhibitor

Question 8

Basiliximab

Answer 8

Anti CD25 - inhibits T cell proliferation

Allograft rejection

Question 9

Abatacept

Answer 9

Anti CTLA4 Ig, reduces T cell activation

RA

Question 10

Rituximab

Answer 10

Anti CD20, depletes mature B cells (not plasma cells)

Lymphoma, RA, SLE

Question 11

Natalizumab

Answer 11

Anti-alpha4 integrin (binds to VCAM1 and MadCAM1 to mediate rolling/arrest of leukocytes), inhibits T cell migration

Relapsing remitting MS, Crohns

Question 12

Tocilizumab

Answer 12

Anti IL6R, reduces macrophage, T, B and neutrophil activation

Castleman’s
RA

Question 13

Muromonab CD3

Answer 13

Blocks CD3 on T cells

Question 14

Anti thymocyte globulin (ATG)

Answer 14

Lymphocyte depletion, modulation of T cell activation and migration

Question 15

Daclizumab

Answer 15

IL2R Ab, targets CD25

Question 16

Efalizumab

Answer 16

Anti CD2a, inhibits migration of T cells

Question 17

Alemtuzumab (Campath)

Answer 17

Monoclonal Ab that binds to CD52, results in lymphocyte depletion

Question 18

Anti TNFalpha agents

Answer 18

Infliximab
Adalimumab
Certolizumab
Golimumab

Rheumatoid arthritis, Ankylosing spondylitis, Psoriasis, psoriatic arthritis, Inflammatory bowel disease

Infusion/injection site reactions, Infection (TB, HBV, HCV), Lupus-like conditions, Demyelination, Malignancy (lymphoma)

Question 19

Etanercept

Answer 19

TNFalpha/TNFbeta receptor p75-IgG fusion protein

Question 20

Ustekinumab

Answer 20

anti-IL-12 and IL-23 (binds to p40 subunit)

Question 21

Secukinumab

Answer 21

Anti-IL-17A

Question 22

Denosumab

Answer 22

anti-RANK ligand antibody, Inhibits RANK mediated osteoclast differentiation and function

Osteoporosis, MM, bone mets

Infection, avascular necrosis of jaw