Ch 55 Drug Table - Drugs that Modulate Immune Function

Glucocorticoids?

Prednisone

Prednisone MOA?

activation of glucocorticoid receptor leads to altered gene transcription

Clinical applications of Prednisone?

1. many inflammatory conditions

2. organ transplantation

3. hematologic cancers

PK of Prednisone?

duration of activity is longer than half-life of drug owing to gene transcription effects

Toxicities, Drug Ix of Prednisone?

1. adrenal suppression

2. growth inhibition

3. muscle wasting

4. osteoporosis

5. salt retention

6. glucose intolerance

7. behavioral changes

Immunophilin ligands?

1. Cyclosporine

2. Tacrolimus

3. Sirolimus

MOA of Cyclosporine?

complex of cyclosporine-cyclophilin inhibits calcineurin

Clinical applications of Cyclosporine?

1. organ transplantation

2. graft vs host disease

3. some autoimmune diseases

PK of Cyclosporine?

1. metabolized by P450 system

2. many drug-drug interactions

Toxicities, Ix of Cyclosporine?

1. renal dysfunction

2. hypertension

3. neurotoxicity

Like Cyclosporine but inhibits Calcineurin by binding to FK506 immunophilin?

Tacrolimus

Its binding to Cyclophilin inhibits the IL-2 signaling pathway; toxicity effects include hypertriglyceridemia, hepatotoxicity, diarrhea, and myelosuppression?

Sirolimus

Purine antagonist?

Mycophenolate mofetil

MOA of Mycophenolate Mofetil?

blocks de novo GTP synthesis by inhibiting inosine monophosphate dehydrogenase

Clinical applications of Mycophenolate Mofetil?

1. organ transplantation

2. graft vs host disease

3. some autoimmune diseases

PK of Mycophenolate Mofetil?

oral, parenteral

Toxicities, Ix of Mycophenolate Mofetil?

1. GI disturbances

2. myelosuppression

MOA of Thalidomide?

complex immune effects including reduction in TNF-alpha production

Clinical applications of Thalidomide?

1. erythema nodosum leprosum

2. multiple myeloma

PK of Thalidomide?

oral

Toxicities, Ix of Thalidomide?

1. teratogen

2. somnolence

3. peripheral neuropathy

4. neutropenia

Thalidomide analog approved for multiple myeloma?

Lenalidomide

CD2-receptor antagonist?

Alefacept (withdrawn)

MOA of Alefacept (withdrawn)?

binds to T-cell CD2 receptor and blocks its association with LFA-3

Clinical applications of Alefacept (withdrawn)?

psoriasis

PK of Alefacept (withdrawn)?

recombinant protein, parenteral

Toxicities, Ix of Alefacept (withdrawn)?

1. reduced T-cell count

2. hepatotoxicity

3. hypersensitivity reaction

4. infection

5. malignancy (withdrawn from market)

Immunsuppressive antisera?

1. Antithymocyte globulin

2. Antilymphocyte globulin

3. Immune globulin intravenous (IGIV)

MOA of antithymocyte globulin?

binds to T cells and triggers complement-based cytotoxicity

Clinical applications of antithymocyte globulin?

transplantation

PK of antithymocyte globulin?

parenteral

Toxicities, Ix of antithymocyte globulin?

1. hypersensitivity reaction

2. injection site reaction

3. malignancy

Immunoglobulin preparation of pooled IgG from healthy donors; wide range of clinical applications including immunoglobulin deficiencies and autoimmune disorders?

immune globulin intravenous (IGIV)

Anti-Rho (D) antibody?

Rho-GAM

MOA of Rho-GAM?

prevents Rh sensitization by binding to Rho(D) antigens

Clinical applications of Rho-GAM?

administered to Rho(D)-negative mothers who carry a Rho(D)-positive fetus 24 - 72 hours after delivery

PK of Rho-GAM?

parenteral

Toxicities, Ix of Rho-GAM?

1. injection-site reactions

2. hemolysis if given to Rh-positive person

IL-1 antagonists?

1. Anakinra

2. Rilonacept

3. Canakinumab

MOA of Anakinra?

recombinant form of the naturally occurring IL-1 receptor antagonist

Clinical applications of Anakinra?

used for rheumatoid arthritis patients who have failed treatment with one or more disease-modifying anti rheumatic drugs

PK of Anakinra?

parenteral

Toxicities, Ix of Anakinra?

monitor for infections

IL-2 antagonists?

1. Dacilzumab (withdrawn)

2. Basiliximab

MOA of Daclizumab (withdrawn)?

MAb that blocks the T-cell IL-2 receptor

Clinical applications of Daclizumab (withdrawn)?

renal transplantation

PK of Daclizumab (withdrawn)?

parenteral

Toxicities, Ix of Daclizumab (withdrawn)?

1. hypersensitivity reactions

2. infection

3. malignancy (withdrawn from market)

Chemical MAb similar to Daclizumab?

Basiliximab

IL-2 agonists?

Aldesleukin

MOA of Aldesleukin?

activates IL-2 receptors on T, B and NK cells

Clinical applications of Aldesleukin?

1. renal cell carcinoma

2. melanoma

PK of Aldesleukin?

parenteral

Toxicities, Ix of Aldesleukin?

1. capillary leak syndrome

2. exacerbation of preexisting inflammatory/autoimmune diseases

3. hypersensitivity reactions

IL-5 antagonists?

1. Mepolizumab

2. Reslizumab

MOA of Mepolizumab?

binds and neutralizes the biological activity of IL-5

Clinical applications of Mepolizumab?

severe eosinophilic asthma

PK of Mepolizumab?

parenteral

Toxicities, Ix of Mepolizumab?

hypersensitivity reactions

IL-6 antagonists?

1. Siltuximab

2. Tocilizumab

MOA of Siltuximab?

binds and neutralizes the biological activity of IL-6

Clinical applications of Siltuximab?

Multicentric Castleman's disease

PK of Siltuximab?

parenteral

Toxicities, Ix of Siltuximab?

hypersensitivity reactions

IL-17 antagonists?

1. Ixekizumab

2. Secukinumab

3. Brodalumab

MOA of Ixekizumab?

binds and neutralizes the biological activity of IL-17

Clinical applications of Ixekizumab?

moderate to severe plaque psoriasis

PK of Ixekizumab?

parenteral

Toxcities, Ix of Ixekizumab?

hypersensitivity reactions

IL-12 & 23 antagonists?

Ustekinumab

MOA of Ustekinumab?

binds and neutralizes the biological activity of IL-12 & IL-23

Clinical applications of Ustekinumab?

plaque psoriasis

PK of Ustekinumab?

parenteral

Toxicities, Ix of Ustekinumab?

hypersensitivity reactions

Anti-IgE?

Omalizumab

MOA of Omalizumab?

binds to IgE and prevents it from activating mast cells and basophils

Clinical applications of Omalizumab?

severe asthma

PK of Omalizumab?

parenteral

Toxicities, Ix of Omalizumab?

hypersensitivity reactions

Anti-integrins?

Natalizumab

MOA of Natalizumab?

humanized IgG4 monoclonal antibody that binds to the a4-subunit of a4B1 and a4B7 integrals expressed on the surface of all leukocytes except neutrophils

Clinical applications of Natalizumab?

drug resistant multiple scelrosis and Chron's disease

PK of Natalizumab?

parenteral

Toxicities, Ix of Natalizumab?

hypersensitivity reactions

Anti B cell activating factor?

Belimumab

MOA of Belimumab?

MAb that inhibits B cell activating factor, also known as B lymphocyte stimulator

Clinical applications of Belimumab?

active, autoantibody-positive systemic lupus erythematous (SLE)

PK of Belimumab?

parenteral

Toxicities, Ix of Belimumab?

hypersensitivity reactions

Anti-TNF-alpha agents?

1. Infliximab

2. Adalimumab

3. Etanercept

4. Golimumab

5. Certolizumab

MOA of Infliximab?

MAb binds to TNF-a and prevents it from activating TNF-a receptor

Clinical applications of Infliximab?

1. inflammatory bowel disease

2. rheumatoid arthritis

3. ankylosing spondylitis

4. psoriatic arthritis

PK of Infliximab?

parenteral

Toxicities, Ix of Infliximab?

1. hypersensitivity reactions

2. infection

3. malignancy

4. reactivation of latent TB

Human MAb similar to Daclizumab?

Adalimumab

Dimer of human TNF receptor fused to IgG constant region?

Etanercept

Human IgG MAb against TNF?

Golimumab

Certolizumab?

humanized Fab fragment binds to TNF

Interferons (IFNs)?

1. interferon-a-2a

2. interferon-a-1b

3. interferon-gamma-1b

MOA of interferon-a-2a?

enhances immune responses by activating IFN-a receptors