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Flashcards in Immunopharmacology Deck (18):

How do they work, side effects,example of one

Agents that inhibit gene expression
- Immunosuppressive -> suppress activation of Innate and adaptive immune cells.
-anti-inflammatory -> down regulate expression of inflammatory mediators - TNF, interleukin. Inhibit phospholipase A2 leading to decreased eicosanoid production

- T cells are more affected but primary and secondary antibody response can be diminished with continued use.
- tapered termination
- cushingoid, mood swings, diabetes, reduced resistance to infections, osteoporosis, cataracts, weight gain and hypertension




Depletion of expanding T cells ( cytotoxic agents)

- converted to mercaptopurine slowly not by enzymes
- interferes with purine nuclei acid synthesis ->lymphocytes need high levels of purines.

Used for kidney transplant and autoimmune diseases


Side effects and drug interactions of Azathioprine

Bone marrow suppression and rash

Drug interaction: allopurinol bc it inhibits xanthine oxidase which converts mercaptopurine to 6-thoiuric acid for excretion and inhibiting it will cause toxicity.


Mycophenolate mofetil -> mycophenolic acid

Cytotoxic agent

- blocks de novo purine synthesis by inhibiting inosine monophosphate dehydrogenase ( IMPDH) the rate limiting step in guanosine synthesis
- lymphocytes depend on de novo synthesis and requires IMPDH . And specifically IMPDHII which Is primarily in lymphocytes.

Better tolerated than Azathioprine bc it's specific for lymphocytes but can also cause apoptosis

More efficacious than Azathioprinei n preventing rejection off kidney transplants .

GI disturbance, headaches, hypertension


Methotrexate and cyclophosphamide

Other cytotoxic agents that are used for (RA and psoriasis)and (cancer and sle ) respectfully


Cyclosporine (a) MOA

Inhibits lymphocyte signaling
- binds to cyclophilin which binds to calcineurin and inhibits it. ( normally calineurin dephosphorylats NFAT to active it and allow it to induce the transcription of IL-2 gene. )


Use , adverse effects of cyclosporine

Organ transplant, graft vs host , RA , rare autoimmune disease

Ae: Nephrotoxicity ( causes vasoconstriction of afferent arteries) hypertension, hyperlipidemia, neurotoxicity, and hepatotoxicity, predisposes pt to viral infection and lymphoma

Metabolized by p450


Tacrolimus (FK506)

Very similar. MOA as cyclosporine. But 10-100x more potent. It binds to FK- binding protein which also inhibits calcineurin.

Highly selective to inhibit IL-3, IL-4, IFN-gamma and TNF-alpha.

Used in the same situations as cyclosporine but is now considered a standard prophylactic agent + others for graft vs host disease. Topical for eczema and psoriasis.

Similar ae but more severe due to enhanced potency


Sirolimus (rapamycin) MOA

MOA: binds to FKBP but the drug/ FKBP complexion inhibits the molecular target mTOR that would normal phosphorylate p70 S6 kinase and PHAS-1 ( phos releases a initiation factor for translation) . The end result is the inhibition of IL-2 stimulated protein synthesis arresting lymphocytes in G1


Sirolimus- side effects, uses

Metabolized by P450 - drug interactions
Side effects - hyperlipidemia, leukopenia, thrombocytopenia, hepatotoxicity but NOT Nephrotoxicity.

Use: in combo with cyclosporine and corticosteroids to prevent rejections of solid organ transplants. And inhibits smooth muscle proliferation it can be used in Sirolimus- eluting stents

When used with cyclosporine this pts have worse renal impairment than when cyclosporine is used alone



Monoclonal antibody directed towards CD3 ( a surface protein on helper and cytotoxic T cells)
-it also suppresses T cell mediated responses to transplants. It depletes T cells through the antibody mediated activation of compliment.

- used for preparation and may be used to prevent acute rejection. Can be used to deplete T cells from the donor bone marrow prior to transplantation
-causes transient immunosuppression can cause cytokines release syndrome - fever, myalgia, nausea, diarrhea .

- antibodies can be generated to OKT3- mouse ab



Antithymocyte ab and anti lymphocyte ab
- raised against whole human lymphocytes by injecting rabbits or other large animals. The ab are polyclonal and so target many epitopes. The ab act on long lived peripheral lymphocytes and have little effect on B cells .

Same uses and side effects as okt3 but broader immunosuppression because it's polyclonal.


Anti- CD25 mAB - daclizumab and basiliximab

Humanize antibodies against cd25, the il-2 receptor which is only expressed in activated T cells

Used in induction and in combo with other agents to prevent rejection.

B: chimer 25 mouse 75 human - 10x more. Potent
D: 90 human



Inhibits co-stimulation.

Ab like molecule consists of CTL-4 (CD28) linked to IgG1 region this interacts with B7 on the APC -> preventing co- stimulation

Clinical trials - looks promising for organ transplantation.


Drugs used in preparation for transplant

Daclizumab, ATG or anti-CD3


Drugs used in hyperacute and chronic rejections

None it cant be stopped


Drugs used in acute rejection

Calcineurin inhibitors ( cyclosporine or tacrolimus) + cell cycle inhibitor ( mycophenolate mofetil or Sirolimus) +\- steroids


Drugs used in graft vs host disease

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