B: 29-31

Question 1

Cytotoxic agents and MOA

Answer 1

Cyclophosphamide- Alklyting. Adds on Guanine N7

Methotrexate- Inhib. DHFR (antimetabolite)

Azathioprine- –> 6MP inhibits purine synt.

Mycophenolic acid- Inhibits GTP synt.

Leflunomide- inhibits pyrimidine synt.

CAMML- גמלים יש מפרקים כאלו מוזרים כמו ראומטויד ארטרייטיס שצריך לטפל בזה עם חומרים סיטוטוקסיים

Question 2

Cyclophosphamide SE and how to prevent

Answer 2

Hemorrhagic cyctitis
Give Mesna

Question 3

Which drug intrferes with Azathioprine metab.?

Answer 3

Allopurinol
inhibits 6-mp metabolism –> elevated level with increased toxicity risk

Question 4

Inhib. of Cytokine gene expression and MOA

Answer 4

Cyclosporine- inhib. Calcineurin. Decrease IL2/3..
binds cyclophillin

Tacrolimus- inhib. Calcineurin. Binds FKBP506. taKKrolimus

Sirolimus- mTOR inhib. Stent!! mTOR is important SIR
binds FKBP 12; Inhibit T-cell proliferation

Tofacitinib- JAK inhib. JAK took all the tofi!

i eat in a Cycle Taco and Tofi in a Sir

Question 5

Tofacitinib indications

Answer 5

Autoimmune

• rhematoid arthritis
• IBD
• Anklylosing spondolitis

Monotherapy OR in combo w/ MTX

בגלל שג’ק אכל את כל הטופי נהייתה לו מחלה אוטואימיונית

Question 6

5 ASA derivative for autoimmune disease and MOA
Indication

Answer 6

Sulfasalazine
PPAR-y agonist (Reduce NFKb, TLR)
reduce cytokine expression
COX , LOX inhib.
Anti-oxidant

For autoimmune
For IBD (UC\>\>CD)

Question 7

Cyclosporine and Tacrolimus inhibit

Answer 7

Calcineurin

(Normally activates T cells)

Question 8

Cyclosporine and Tacrolimus SE

Answer 8

Nephrotoxicity

Cyclosporine:

• hepatotoxic
• Hypertension
• gingival hypertrophy
• Nephrotoxic

Tacrolimus:
-Nephrotoxic

Question 9

Immunotherapy- Fusion and Ab and MOA

Answer 9

Rituximab- anti CD20. reduce B. Ritux reduce B

Infliximab, Adalimumab- Anti TNFa

Toclizumab- Anti IL6. T+B

Ustekinumab- Anti IL12.,IL-23 inhib TH1 , TH17
אוזבקים צריכים עזרה

Natalizumab- Inhibit T cell anti-integrin ( a4b1 integrin) נטטטלי

Dupilumab- Anti IL4 די זה האות הרביעית

Abatacept- CTLA-4 Fusion protein , inhib. CD28 on T cell.

אבא תצא! הפיוזון הזה לא טוב לך. אבטצפת הכי לא קשור

ximab is chimeric
umab is fully human
zumab is huminized

Question 10

Immunotherapy- Fusion and Ab and common SE

Answer 10

Injection side reaction
Infections

Question 11

Immunotherapy- Fusion and Ab and indication

Answer 11

• Rituximab-
  
  • B cell lymphoma
  • autoimmune (RA, vasculitis)
  • solid organ transplantation
• Infliximab
  
  • autoimmune (RA, ankylosing spondylitis, psoriasis)
  • IBD
• Adalimumab-:
  
  • RA
• Toclizumab-
  
  • RA
  • Jevunile idiopathic arthritis
• Ustekinumab-
  
  • Chron’s
  • psoriasis ( plaque , psoriatic arthritis)
• Natalizumab-
  
  • Multiple sclerosis
  • Crohns
• Dupilumab-
  
  • Atopic DDDermatitis
• Abatacept-(CTLA4 fusion protein)
  
  • RA
  • Jevunile idiopathic arthritis
  • psoriasis

Question 12

Anti Thymocyte Globulin(ATG)

mechanism

administration

indication

SE

Answer 12

• Type of anti-sera against lymphocytes
• produced in horse, sheep, rabbits by immunization against human lymphoid cells
• mechanism: (Selective inhibition of cellular immunity rather than antibody formation)
  
  • Binds to T cells and triggers complement-based cytotoxicity
  • Antibody binds T-cells involved in antigen recognition –> destruct them by serum complement
• administration: Parenteral
• indication:
  
  • Stem cell Transplantation (prevent graft-vs-host)
  • solid organ transplantation
  • primary aplastic anemia (immune-mediated process)
• SE
  
  • Hypersensitivity to injection
    
    • serum sickness
    • anaphylaxis
  • pain, eythemia at injection site
  • lymphoma (late complication)

Question 13

Immunotherapy- Fusion and Ab

Side effects

Answer 13

• Rituximab
  
  • Injection site rxn
  • infections
  • complete recovery of B-cell may take up to 6m
• Infliximab, Adalimumab-
  
  • injection site rxn
  • infections (opportunistic)
  • Reactivation of latent TB
  • lymphoma
• Toclizumab-
  
  • Injection site rxn
  • Infections
  • neutropenia
• Ustekinumab-
  
  • Injection site rxn
  • infections
• Natalizumab-
  
  • Injection site rxn
  • infection
  • reactivation of JC virus may develop PML (progressive multifocal leukoencephalopathy) = demyelinating disease affecting CNS white matter
• Dupilumab-
  
  • Allergic rxn
  • conjuctivitis
  • keratitis
• Abatacept-(CTLA4 fusion protein)
  
  • Injections
  • production of neurtalizing antibodies

Question 14

ALL anti-TNFalpha agents have risk of causing?

Answer 14

• high risk of serious infections
• reactivation of TB
• lymphoma

eg.Etanercept

Certolizumab, golimumab

Question 15

Abatacept

mechanism and characteristics

Answer 15

• mechanism:
  
  • prevents T-cell CD28 from binding APC CD80/86,
  • CTLA4 fusion protein binds CD80/86 on APC
  • inhibit T-cell co-stimulatory signal ( CD28 receptors of Tcells)
• Characteristics:
  
  • EC domain of CTLA-4 fused to human IgG Fc
  • Blocks T-cell activation by interfering with the interaction of Tcell CD28 to APC CD80/86
  • FOR SEVERE Rhematoid arthritis