Immunopharmacology

IMMUNOPHARMACOLOGY Ma. Janetth B. Serrano, M.D., DPBA

IMMUNOPHARMACOLOGY 2 major components of the immune system: INNATE Physical – skin, mucus membrane Biochemical – complement, lyzosyme Cellular – macrophages, neutrophils ADAPTIVE Antibodies – HUMORAL immunity T-lymphocyte – CELL MEDIATED immunity

COMPLEMENTS in Innate Immunity: 1. C3a, C5a  chemotaxis 2. C3b  opsonization 3. C5b, C6, C7, C8, C9  MAC IMMUNOPHARMACOLOGY

IMMUNOPHARMACOLOGY 0psonized bacteria Macrophage APC T lymphocyte IL-2 IL-2 IFN-  Activated Macrophage Activated NK cells Activated Cytotoxic T cell CELL-MEDIATED IMMUNITY B lymphocyte IL-4,IL-5 TH 1 TH 2 Memory B Cells Plasma Cells: IgG - IgM IgA - IgD HUMORAL IMMUNITY IFN-  TNF-  IFN- 

T-helper cells: 1. T H 1 subset - IFN-  , IL-2, TNF-  2. T H 2 subset - IL-4, IL-5, IL-6, IL-10 IMMUNOPHARMACOLOGY

ABNORMAL IMMUNE RESPONSES: HYPERSENSITIVITY AUTOIMMUNITY IMMUNODEFICIENCY IMMUNOPHARMACOLOGY

1. Corticosteroids 2. Cyclosporine 3. Sirolimus 4. Tacrolimus 5. Interferons 6. TNF-alpha binding drugs 7. Mycophenolate mofetil 8. 15-Deoxyspergualin 9. Thalidomide 10. Glatiramer Immunosuppressants IMMUNOPHARMACOLOGY

Corticosteroids MOA: inhibit T-cell proliferation & T-cell dependent immunity Inhibit expression of genes encoding cytokines Inhibit production of inflammatory mediators Affects cell-mediated immunity more than humoral immunity IMMUNOPHARMACOLOGY

Continuous administration: ↑ fractional catabolic rate of IgG Indications: Autoimmune disorders - autoimmune hemolytic anemia, LE - ITP, Inflammatory Bowel Dse,, Hashimoto’s Modulate allergic reactions - asthma Organ transplantation – rejection crisis IMMUNOPHARMACOLOGY Corticosteroids

Immunosuppressive dose: 10-100 mg/day Adverse effects: GI bleeding adrenal suppression fluid retention diabetes proximal muscle wasting superinfections IMMUNOPHARMACOLOGY Corticosteroids

Blocks T-cell activation binds to cyclophillin  inhibits calcineurin activity  inhibits gene transcription of IL-2, IL-3, IFN  & other factors Most commonly used immunosuppresant for renal transplantation Indications: transplant rejection (kidney, liver, pancreas, cardiac) Autoimmune disorders (uveitis, RA, DM type1) Toxicities: nephrotoxicity, hyperglycemia, hyperlipidemia, osteoporosis, ↑ hair growth, transient liver dysfunction IMMUNOPHARMACOLOGY Cyclosporin

Tacrolimus Binds to FK-binding protein  inhibits T-cell activation 10-100 times more potent than cyclosporine Liver & kidney transplant Oral or IV : t½ = 9-12 hrs Toxicity: nephrotoxicity, neurotoxicity, hyperglycemia, GI dysfunction IMMUNOPHARMACOLOGY

Binds also to immunophyllin  blocks the response of T-cell to cytokines Potent inhibitor of B-cell proliferation & Ig production Indications: Kidney & heart allografts C syclosporin  psoriasis & uveoretinitis IMMUNOPHARMACOLOGY Sirolimus (rapamycin)

Type 1: induced by viral inf. IFN-alpha  prod. by leukocytes IFN-beta  fibroblasts & epithelial cells Type 2: IFN-gamma  produced by activated T-lymphocytes Indications: cancer IFN-   multiple sclerosis IFN-   chronic granulomatous disease IMMUNOPHARMACOLOGY Interferons

INFLIXIMAB Chimeric IgG1 monoclonal antibody with human region & murine regions Suppress generation of cytokines Crohn’s disease; RA ETANERCEPT Chimeric protein with human regiom Similar MOA with infliximab but shorter half-life RA IMMUNOPHARMACOLOGY TNF- α binding drugs

Inhibits a series of T & B lymphocyte responses Inhibit de novo pathway of purine synthesis Renal & heart transplantation Mizoribine – inh. nucleotide synthesis PW; kidney transplants Brequinar Sodium – inh. de novo pathway of pyrimidine synthesi; cancer & organ transplantation IMMUNOPHARMACOLOGY Mycophenolate Mofetil

Potent antimonocytic & antilymphocytic effect Inhibits T & B lymphocyte response Renal transplants; pancreas & heart transplants IMMUNOPHARMACOLOGY 15-Deoxyspergualin

Sedative drug Favors TH2 over TH1 Suppress TNF- α production Antiangiogenesis action: teratogenicity & anticancer Indications Erythema nodosum leprosum (skin manifestations of SLE) Lung transplantation IMMUNOPHARMACOLOGY Thalidomide

Relapsing-remitting form of multiple sclerosis Subcutaneous injection Toxicities: Transient post-injection reaction IMMUNOPHARMACOLOGY Glatiramer

1. Azathioprine 2. Leflunomide 3. Cyclophosphamide IMMUNOPHARMACOLOGY CYTOTOXIC Agents:

Metabolized to 6-mercaptopurines Inhibit purine synthesis  interferes with nucleic acid metabolism  inhibits cellular & humoral responses Highly teratogenic Well absorbed from GI tract IMMUNOPHARMACOLOGY Azathioprine

Renal allograft, AGN, SLE(renal), RA, Crohn’s disease Prednisone-resistant antibody-mediated ITP Autoimmune hemolytic anemia Toxicities: Bone marrow suppression GI disturbances: N&V, diarrhea Skin rashes, drug fever, hepatic dysfunction IMMUNOPHARMACOLOGY Azathioprine

Prodrug of an inhibitor of pyrimidine synthesis Inhibits lymphoid cells Orally active RA Toxicities: Headache, nausea & diarrhea Hepatic dysfunction, renal impairment Teratogenic IMMUNOPHARMACOLOGY Leflunomide

Most potent immunosuppressive drug Destroys proliferating lymphoid cells Autoimmune disorders: SLE Acquired factor XIII antibodies Bleeding syndromes Toxicities: Pancytopenia, hemorrhagic cystitis IMMUNOPHARMACOLOGY Cyclophosphamide

Antibodies as Immunosuppressive Agents Antilymphocytic antibody Immune Globulin IV Hyperimmune Immunoglobulins Monoclonal Antibodies Rh o (D) Immune Globulin Micro-Dose Prevention of hemolytic disease of the newborn Given to mother within 72 hrs after delivery of an Rh-negative baby IMMUNOPHARMACOLOGY

1.Muromonab- CD3 2. Palivizumab 3. Rituxumab 4.Trastuzumab IMMUNOPHARMACOLOGY MONOCLONAL ANTIBODIES :

T-cell specific antibody Renal transplantation, heart / renal IMMUNOPHARMACOLOGY Muromonab-CD3

Palivizumab – RSV Rituximab – follicular B-cell non-hodgekins lymphma Trastuzumab – metastatic breast CA IMMUNOPHARMACOLOGY

IMMUNOMODULATORS CYTOKINES Interferon-alpha: - hairy cell leukemia - chronic myelogenous leukemia - malignant melanoma - Kaposi’s sarcoma - anticancer  renal cell CA, carcinoid syndrome, T cell leukemia

IMMUNOMODULATORS CYTOKINES Melanoma and Prostate cancer GM-CSF (+) effects in response to Hep B vaccine Interferons & IL-2 Malignant melanoma Soft tissue sarcoma of extremities TNF-alpha Metastatic renal cell CA Malignant melanoma Interleukin-2 Chronic granulomatous disease Interferon-gamma Relapsing type multiple sclerosis Interferon-beta

IMMUNOPHARMACOLOGY IMMUNOMODULATORS IMMUNOPHARMACOLOGY LEVAMISOLE: - antiparasitic agent - potentiate action of fluorouracil in adjuvant therapy of Dukes class C colorectal CA - other uses: > hodgkin’s lymphoma > RA

IMMUNOPHARMACOLOGY IMMUNOMODULATORS IMMUNOPHARMACOLOGY BCG (Bacille-Camille-Guarin): - immunization against tuberculosis - Adjuvant in intravesical therapy for SF bladder CA

IMMUNOPHARMACOLOGY IMMUNOMODULATORS IMMUNOPHARMACOLOGY HIV: - Inosiplex - Diethylcarbamate (DTC) DiGeorge Syndrome of T cell deficiency - give THYMOSIN

The winds and waves are always on the side of the ablest navigator “ The winds and waves are always on the side of the ablest navigator”

QUIZ Most common adverse effect of corticosteroids The most potent immunosuppressive agent. Adverse effects of CYCLOPHOSPHAMIDE Given to mothers to prevent ‘hemolytic disease of the newborn’ Write B if the drug inhibits B lymphocytes & its responses; T if the drug inhibits T lymphocytes & its responses; and C if it inhibits both T & B cells: 6. Tacrolimus 9. Azathioprine 7. Leflunamide 10. Cyclophosphamide 8. Cyclosporin

Immunopharmacology

More Related Content

What's hot

Similar to Immunopharmacology

More from MD Specialclass

Recently uploaded

In this document

Immunopharmacology