Antibody Immunosuppressants

Question 1

Muronomab CD3, OKT3

Answer 1

1. MOA: Mouse monoclonal ab to CD3 of Tcells, blocks activity of T cells and prevents new production.
2. Kinetics: IV injection for 10-14 days
3. SE: Cytokine release syndrome: ranges from flu like response to shock. Fever/chils, nausea, chest pain/dyspnea, rarely severe pulmonary edema. Can have severe rxn to mouse abs, must pretreat w/corticosteroids.
4. Uses: steroid resistant acute rejection episodes

Question 2

Daclizumab (humanized), Basiliximab (chimeric)

Answer 2

1. MOA: Binds to IL-2 receptors on activated T cells, inhibit further activation.
2. Kinetics: injection, long t1/2 –> effect lasts for 4-6 weeks after 2 infusions.
3. SE: very minimal
4. Uses: prophylaxis before transplant, combined with cylcosporine and coritcosteroids.

Question 3

Efalizumab

Answer 3

1. MOA: Anti-CD11a mab, prevents binding of LFA-1 to ICAM-1
2. Kinetics: SubQ once per week
3. SE: first dose effect; HA, fever/chills, N/V, myalgias, inc incidence of URI.
4. Use: Plaque psoriasis (ICAM-1 is upregulated on endothelium and keratinocytes).

Question 4

Alefacept

Answer 4

1. MOA: Human fusion protein, binds to CD2 on cell surface preveting activation of T cells. Reduces circulating T cells especially those in psoriatic plaques.
2. T cell count must be monitored during therapy
3. Used for tx of plaque psoriasis.

Question 5

Lymphocyte Immune Globulin, Antithymocyte Globulin

Answer 5

1. MOA: IgG ab to T cells, binds to T cells reducing circulating numbers of lymphs and impairs T cell response.
2. Kinetics: Administered IV over several hours for a period of 7-14 days. Admin w/ steroids and cytotoxic drugs to minimize response to equine globulin.
3. SE: Must do skin test first to check sensitivity to foreign protein, can have severe rxn to it (fever, chills, hypotension, rash). Possible lymphomas at injection site, renal toxicity.
4. Uses: Acute rejection. Impairs delayed hypersensitivity and cellular immunity. Allows for removal of tacolimus/cyclosporine to recover renal function.

Question 6

Ustekinumab

Answer 6

1. MOA: blocks IL-12 and IL-23 from binding to receptors, inhibits signaling in lymphocytes. Faster response than TNFa drugs.
2. Plaque Psoriasis

Question 7

Omalizumab

Answer 7

1. MOA: blocks IgE from binding to mast cells and basophils. Decreases total IgE in serum for up to a year after injection.
2. Use: allergic asthma where steroids are no longer effective.

Question 8

RA ab meds

Answer 8

Adalimumab, cetoizumab pegol, etanercept, golimumab, infliximab all bind to TNF-a and are used in the tx of RA. Abatacept is a fusion protien. Tocluzumab is a recombinatn humanized IgG1 that binds to IL-6 recetors.

Question 9

Rho(D) Immue globulin

Answer 9

1. MOA: Prevents immune response to Rho antigen by binding to the antigen from the child which prevents formation of anti-Rh abs by mother.
2. Kinetics: IM to Rh neg mother within 72 hrs after birth of child.
3. SE: mild adverse rxn at site of injection. Slight elevation of temperature. Anaphylaxis is rare.
4. Uses: see kinetics, also after abortion or miscarriage, also post-maternal exposure to fetal blood (amniocentesis, ectopic, abdominal trauma during pregnancy).
5. CI: Rh positive pts and Rh neg pts who have already developed anti-Rh abs

Question 10

Natalizumab

Answer 10

1. MOA: binds to a4b7 integrins on all leukocytes except neutrophils.
2. Use: Crohns and MS
3. CI: not sued with anti-TNFa drugs

Question 11

Vedlizumab

Answer 11

1. Tagets a4b7 integrin in the GI but doesnt cuase systemic immunosuppression.