Immune Mod Therapies 2

Question 1

What are corticosteroids?

Answer 1

Synthetic glucocorticoids based on naturally occurring steroids
NO mineralocorticoid axrtivity

Question 2

What structures do corticosteroids have an effect on?

Answer 2

Prostaglandins
Phagocytes
Lymphocytes

Question 3

What is corticosteroid effect on prostaglandins?

Answer 3

Corticosteroids inhibit phospholipase A2
Phospholipase A2 is usually converts phospholipids into arachidonic acid
AA is then converted to eicosainoids (prostaglandins, leukotrienes) by COX
Therefore by blocking phospholipase, no prostaglandins are produced, reducing inflammation

Question 4

What is corticosteroid effect on phagocytes?

Answer 4

Decreases phagocytes to inflamed tissue (due to reduced signals to phagocytes)

Decreased phagocytosis

Decreased proteolytic enzymes

Question 5

What is corticosteroid effect on lymphocyte function?

Answer 5

Lymphopoenia (sequestration of lymphocytes in lymphoid tissue)
Blocks cytokine gene expression
Decreased antibody production
Promotes apoptosis

Question 6

What are side effects of corticosteroids?

Answer 6

Metabolic - central obesity, moon face, diabetes, lipid disorders, osteoporosis, hirsutism, adrenal suppression

Others - cataracts, glaucoma, peptic ulceration, pancreatitis, avascular necrosis

Immunosuppression

Question 7

What do anti proliferative agents do?

Answer 7

Inhibit lymphocyte proliferation

Question 8

What are examples of anti proliferative agents?

Answer 8

Cyclophosphamide
Mycophenolate
Azathioprine
Methotrexate

Question 9

What is the MOA of antiprolif agents?

Answer 9

Inhibit DNA synthesis (Cells with rapid proliferation are most targeted)

Question 10

What is the MOA of cyclophosphamide?

Answer 10

Alkylates guanine bases of DNA
Damages DNA and prevents cell replication
Affects B cells > T cells
At high dose, affects all cells with high turnover

Question 11

What are major indications for cyclophosphamide=

Answer 11

Multisystem connective tissue disease
Vasculitis with severe end organ involvement
Anti-cancer agents

Question 12

What are side effects of cyclophosphamide?

Answer 12

• Toxic to proliferating cells (bone marrow suppression, sterility, hair loss)
• Haemorrhagic cystitis (as ACROLEIN in excreted in urine)
• Malignancy (bladder cancer, harm cancer, non-melanoma skin cancer)
• Teratogenic
• PCP

Question 13

What is the mechanism of Azathioprine?

Answer 13

Metabolised by liver to 6 mercaptopurine
Blocks de novo purine synthesis
Prevents DNA replication
Preferentially inhibits T cell activation and prolif

Question 14

What are indications of azathioprine

Answer 14

Transplant
AI disease
Autoinflamm disease e.g. Chrons, UC

Question 15

What are side effects of azathioprine?

Answer 15

Bone marrow suppression
Hepatotoxicity
Infection

Question 16

Individuals with what polymorphism are susceptible to bone marrow suppression?

Answer 16

Thiopurine Methyl Transferase

Question 17

What is MOA of mycophenolate mofetil?

Answer 17

Blocks de novo nucleotide synthesis
Prevents DNA replication
Prevents T cell> B cell proliferating

Question 18

What is indications of mycophenolate mofetil?

Answer 18

Transplantation

AI diseaase

Question 19

What are side effects with mycophenolate mofetil?

Answer 19

Bone marrow suppression
Teratogenic
Infection (HSV, mrogressive multifocal leukoencephalopathy)

Question 20

What is the aim of plasmapheresis?

Answer 20

PLASMA EXCHANGE aka remove pathogenic antibodies

Question 21

What occurs in plasmapheresis?

Answer 21

Patient’s blood is passed through a separator
Own cellular components are reinfused
Plasma is treated to remove Ig and then reinfused

Question 22

What is the issue with plasmapheresis and how do you solve it?

Answer 22

Rebound antibody production (because even if you get rid of the antibodies, the plasma cells are still there)

GIVE anti proliferative agent to avoid this

Question 23

What are Indications for plasmapheresis?

Answer 23

Severe antibody-mediated disease

e.g. good pastures, Myasthenia graves, transplant rejection

Question 24

What is the MOA of calcineurin inhibitors?

Answer 24

Inhibit calcineurin > prevent T cell signalling > block IL2 production

Question 25

What are examples of calcineurin inhibitors?

Answer 25

Ciclosporin | Tacrolismus

Question 26

What are SE of calcineurin inhibitors?

Answer 26

``` nephrotoxicity HTN neurotoxic diabetogenic dysmorphic features ```

Question 27

What should you monitor with calcineurin inhibitors=?

Answer 27

BP | Renal function

Question 28

What is an example of a JAK inhibitor?

Answer 28

Tofacitinib (JAK1, JAK3) | What do

Question 29

What does Tofacitinib do?

Answer 29

Interferes with JAK-STAT signalling Influences gene transcription Inhibits production of inflammatory molecules

Question 30

What disease is Tofacitinib good for?

Answer 30

RA

Question 31

What is an example of PDE4 inhibitor?

Answer 31

apremilast

Question 32

What is MOA of PDE4 inhibitors?

Answer 32

PDE4 works in metabolism of cAMP PDE4 inhibitors upregulate cAMP cAMP activates PKA, which prevents activation of transcription factors This leads to a decrease in cytokine production

Question 33

What is anti-thymocyte globulin used for?

Answer 33

Allograft rejection | As it causes T cell depletion

Question 34

What is basiliximab?

Answer 34

an antibody directed at CD25

Question 35

What is basiliximab used for?

Answer 35

For prophylaxis of graft rejection

Question 36

What does basiliximab target?

Answer 36

``` IL2 receptor (called CD25), alpha chain Leads to inhibition of T cell proliferating ```

Question 37

Side effects of basiliximab

Answer 37

Infusion reaction Infection Concern of long term malignancy

Question 38

how does methotrexate work

Answer 38

ANTI-FOLATE | inhibits dihydrofolate reductase, stopping DNA synthesis

Question 39

what must you give with methotrex

Answer 39

folate supplement

Question 40

what must you always measure before you prescribe azathioprine

Answer 40

Thiopurine methyl transferase aka TPMT | because people with this variant will be unable to metabolise azathioprine

Question 41

what does rituximab do

Answer 41

blocks CD20 > depletion of mature B cells

Question 42

how does natalizumab work

Answer 42

against a4 integrin

Question 43

what disease does natalizumab work against

Answer 43

MS

Question 44

list some Anti-TNFalpha antibodies

Answer 44

infliximab adalimumab certolizumab golimumab

Question 45

what is the MOA of etanercept

Answer 45

TNF alpha antagonist - mops up TNF alpha > ihibits TNF alpha

Question 46

WHAT IS MOA of denosumab

Answer 46

antibody against RANKL Normally, osteblasts produce RANKL. RANKL binds to RANK > osteoclast differentiation and function > increase bone resorption So denosumab stops osteoclast function > reduces bone resporption

Question 47

what are indications for denosumab

Answer 47

osteoporosis | give subcut every 6 months

Question 48

what is a side. effect of denosumab

Answer 48

avascular necrosis of jaw