Similar to Cyclosporine

Macrolide antibiotic

Binds FK binding proteins that will inhibit calcineurin 

Inhibits IL-3, IL-4, IFN gamma, and TNF-alpha

Used in organ transplantation (especially renal, but also heart and liver; increasingly with bone marrow, lung, and pancreas), also for g vs h often in combo with corticosteroids

Also for psoriasis and RA

Topical prep used for atopic dermatitis (eczema) and psoriasis

very often used when other standard treatments have failed

Similar to cyclosporine - nephrotoxicity (dose related, caused by vasoconstriction), hypertension, hyperlipidemia, neurotoxicity (paresthesia, tremor, and seizures), and hepatotoxicity 

Predisposes patients to viral infection and lymphoma

Often stronger side effects because more potent of a drug than cyclosporine

Either use alone or in combination with other agents (cyclosporine and corticosteroids) to prevent rejection of solid organ transplants

Also inhibits proliferation of smooth muscle cells, so can be used in sirolimus-eluting stents 

Still used in combination with cyclosporine, but the calcineurin inhibitor is at a lower dose plus a glucocorticoid

Levels of drug and kidney function needs to be monitored closely;  if someone is at high risk of nephrotoxicity, instead of using cyclosporine with sirolimus, use glucocorticoids and mycophenolate 

Selective depletion of T cells

Directed towards CD3 - surface protein on helper and cytotoxic T cells; also suppresses T cell responses to transplants

Depletes T cells through antibody mediated activation of complement

OKT3 uses

Used for preparation and may be used to prevent acute rejection (renal, hepatic, heart)

Some will be used to deplete T cells from donor bone marrow prior to transplantation

Causes profound immunosuppression, but it is transient 

It's profound

Will first activate T cells before degrading them -- cytokine release syndrome (fever, myalgia, nausea, diarrhea)

Usually occurs after first few doses

It is a mouse anti-human antibody, so body can generate antibodies to it 

Raised against human lymphocytes and are polyclonal - will act on long lived peripheral lymphocytes and will have little effect on B cells

Similar uses to OKT 3: suppress T cell mediated response to transplants (used for preparation and acute rejection); some used to deplete T cells from donor bone marrow prior to transplantation

Similar to OKT3 - cytokine release syndrome)

But much broader immunossuppression because its polyclonal 

Humanized antibodies against CD25, the IL-2 receptor

This protein is only expressed in activated T cells

Used for induction and in combination with other agents to prevent rejection 

Inhibition of costimulation

Consists of CLT-4 and will compete CD28 to bind B7

Prevents costimulation

Cannot be stopped by immunosuppresive drugs

Chronic rejection - activation of T cells - no treatment

Weeks to months

Can be treated generally with immunosuppressive drugs

Calcineurin inhibitor (cyclosporine or tacrolimus) PLUS

cell cycle inhibitor (mycophneolate mofetil or sirolimus) PLUS OR MINUS

Steroids

Major complication of bone marrow and stem cell transplantation

Start with high dose steroids, add drugs such as mycophenolate mofetil, sirolimus, tacrolimus, daclizumab 

Preparation of IG pooled from a large population of donors: 'normalizing serum'

Used at low doses in humoral deficiency

Use at high doses for severe asthma, some autoimmune disorders, Kawasaki syndrome

Concentrated solution of human IgG containing antibodies to Rho(D) antigen of red cell

Prevents sensitization of Rh-negative mother

Administered to mother within 24 to 72 hours after birth of an Rh positive infant

Downregulate expression of TNF and IL

Inhibit phospholipase A2 leading to decreased eicosanoid production

T cells most affected, but primary antibody response will be diminished and eventually secondary antibody response will be too 

used in combination with other immunosuppressants for solid organ transplantation and hematopoietic stem cell transplantation and for certain autoimmune diseases - rheumatoid arthritis, SLE 

Also used in attenuating allergic reactions 

Can cause adrenal suppression, so they must be tapered 

Other problems are: cushingoid reactions, mood swings, diabeedus, reduced resistance to infection, osteoporosis, cataracts, weight gain, and HTN 

Pro-drug slowly converted to mercaptopurine nonenzymatically

Slow action helps immunosuppressive activity 

Interferes with purine nucleic acid synthesis -- required for lymphoid cell proliferation 

Bone marrow suppression (usually leukopenia) and rash

At higher doses, usually GI effects, some hepatotoxicity 

Also acts by blocking de novo purine synthesis 

Inhibits IMPDH (RLS in guanosine synthesis) 

Inhibits II form which is more specific for lymphocytes --- less toxic to other cells 

Cytostatic effect on lmyphocytes but can also cause apoptosis 

Mycophenolate more efficcacious than azathioprine in preventing rejection of kidney transplants; also used for other autoimmune dz 

Methotrexate (rheumatoid arthritis and psoriasis)

Cyclophosphamide (cancers, SLE)