Immunopharmacology - Chapter 55

Decreased synthesis

• - Inhibition of proliferation of T lymphocytes (Decreased cellular immunity),
• - Continuous therapy lowers levels of IgG by increased catabolism of this class of
• immunoglobulins

• Addison’s disease,
• Asthma,
• Arthritis,
• cancer chemotherapy,
• organ transplantation

• - Adrenal suppression,
•  - growth inhibition,
•  - muscle wasting,
•  - osteoporosis,
•  - salt retention,
•  - diabetogenesis,
•  - psychosis

• Fat-soluble peptide antibiotic which blocks the antigen receptor-induced differentiation of T cells.
• Binds to cyclophyllin and inhibits calcineurin
• Inhibits production of IL2, IL3, and IFNγ.

• immunosuppressant in organ transplantation,
• in management of new-onset diabetes,
• and may have a role in the management of asthma

• renal,
• hyperglycemia,
• osteoporosis,
• increased hair growth (in women),
• transient liver dysfunction,
• limb paresthesia,
• distal tremor,
• hallucinations,
• seizures

• - Immunosuppressant macrolide antibiotic,
•  - Binds to FK-binding protein (FKBP),
•  - Inhibits calcineurin which is necessary for activation of a T cell-specific transcription factor. 

–More potent than cyclosporine

Used in liver and kidney transplant recipients

• renal,
• hyperglycemia,
• osteoporosis,
• increased hair growth (in women),
• transient liver dysfunction,
• limb paresthesia,
• distal tremor,
• hallucinations,
• seizures

- Binds to immunophyllins and blocks the response of T cells to cytokines.

 - Potent inhibitor of B cell proliferation and immunoglobulin production

Used alone or in combination with cyclosporine for heart and kidney transplant

• hyperlipidemia, 
• hematopoietic cell toxicity

MYCOPHENOLATE MOFETIL

• - Inhibits a series of T and B cell responses.
•  - Its action depends on its ability to inhibit the de novo pathway of purine synthesis by inhibition of inosine monophosphate dehydrogenase. 

–Lymphocytes are particularly sensitive because they lack the enzymes needed for the alternative salvage pathway for purine synthesis

Has been used successfully as the sole agent in kidney, liver, and heart transplants.

•  - In kidney transplants it has been used with low dose cyclosporine to reduce the incidence of cyclosporine-induced
• nephrotoxicity

• GI distress,
• Myelosuppression

Sedative drug that suppresses TNF production. 

• Leprosy,
• SLE,
• Wasting syndrome in AIDS,
• multiple myeloma

THALIDOMIDE

• - Prodrug of mercaptopurine which is a purine antimetabolite. 
• – It is cytotoxic in the early phase of lymphoid cell production and has a greater effect on T than B cells. 

• –Immunosuppression results from
• interference with nucleic acid metabolism at steps that are required for the wave of lymphoid proliferation which follows antigenic stimulation

• SLE,
• RA,
• Kidney transplants,

Bone marrow suppression, when given with allopurinol the dose must be reduced by 75%

• Transformed by liver enzymes into an alkylating agent. 
• –It is the most potent of the immunosuppressant drugs. 
• –Has greater effect on B than T cells.

• hemolytic anemia,
• antibody-induce red cell aplasia,
• bone marrow transplants,

hemorrhagic cystitis

• Prodrug of an inhibitor of pyrimidine synthesis. 
• It arrests lymphocytes in the G1 phase of the cell cycle

RA

• Alopecia,
• rash,
• and diarrhea

• AKA antithymocyte globulin (ATG) produced in horses by immunization against human thymus cells. 
• Binds to T cells and initiates their destruction by serum complement. 
• Selectively blocks cellular immunity rather than antibody formation.

• Prior to bone marrow transplant of
• suppress graft-vs-host reaction.