Immunopharmacology

1) organ transplantation
2) treatment of autoimmune disorders
3) prevention of Rh hemolytic disease of the newborn

Calcineurin agents:

1) cyclosporine
2) tacrolimus

Cyclosporine and tacrolimus bind to immunophilins (cyclophilin and FKBP, respectively) which leads to the inhibition of calcineurin.

Inhibition of calcineurin blocks the dephosphorylation of NFAT, inhibiting the NFAT from moving into the nucleus.

This movement into the nucleus is essential in the transcription of IL-2 and other growth and differentiation-associted cytokines, but is blocked by cyclosporine and tacrolimus.

These agents may increase cyclosporine elimination:
--phenobarbital
--phenytoin
--carbamazepine
--rifampin
--St.John's wort


These agents may decrease cyclosporine elimination:
--ketoconazole
--erythromycin
--methylprednisolone
--some Ca-channel blockers

TRUE

Sirolimus binds to the immunophilin, FKBP. This complex inhibits mTOR, which is a kinase involved in interleukin-driven T-cell proliferation.

Therapeutic drug monitoring is an essential part of the clinical management of:

f) all of the above

Sirolimus adverse effects inlcude: hyperlipidemia, myelosuppression, inc risk of infections and malignancies


Tacrolimus adverse effects include: renal dysfunciton, HTN, neurotoxicity, hyperglycemia, hyperkalemia

Mycophenolate mofetil is a prodrug that is converted to mycophenolic acid, an active moiety.

Mycophenolic acid inhibits the de novo pathway of guanine nucleotide synthesis by inhibiting the enzyme inosine monophosphate dehydrogenase.

While there is also a salvage pathway in addition to the de novo pathway, B and T cells rely heavily on the latter.

Mycophenolate mofetil can cause these adverse effects:

Answer: b) diarrhea + leukopenia + teratogenic effects

Other answer choices:
a) renal dysfunction + HTN + hyperkalemia = cyclosporine and tacrolimus

c) hyperlipidemia + myelosuppression = sirolimus

Thalidomide is approved for use in

1) multiple myeloma
2) erythema nodosum leprosum

Thalidomide adverse effects:

--teratogenicity
--peripheral neuropathy
--risk of venous thromboembolic events

LENALIDOMIDE is the thalidomide analog that is approved for use in certain myelodysplastic syndromes and multiple myeloma.

This cytotoxic immunosuppressant is converted to 6-mercaptopurine.

c) azathioprine

Antithymocyte globulin is used as an immunosuppressant in the case of transplantation.

FALSE

This is the true statement:
Muromonab-CD3 is a monoclonal antibody that binds to CD3 and is used as an immunosuppressant in the setting of RENAL TRANSPLANT REJECTION.

Which of the following binds the IL-2 receptor and is used in the setting of renal transplantation?

b) basiliximab

Basiliximab and daclizumab:

a) bind IL-2 receptor and are used in the setting of renal transplantation

1) adalimumab
2) etanercept
3) infliximab

Rho (D) immune globulin is used to prevent Rh hemolytic disease of the newborn.

Immunomoduation therapy uses:
1) immunodeficiency
2) chronic infections
3) cancer


Immunosuppressant therapy uses:
1) organ transplantation
2) treatment of autoimmune disorders
3) prevention of Rh hemolytic disease of the newborn

Immunosuppressant agents:
1) corticosteroids
2) calcineurin inhibitors
3) proliferation signal inhibitors
4) mycophenolate mofetil
5) thalidomide
6) cytotoxic drugs
7) antibodies

Immunomodulation agents:
1) interferons
2) interleukin-2

1) binds FKBP to inhibit mTOR and interleukin-driven T cell proliferation = SIROLIMUS

2) cytotoxic agent that is converted to 6-mercaptopurine = AZATHIOPRINE

3) binds cyclophilin and inhibits calcineurin's dephosphorylation of NFAT, leading to the blockade of IL-2 transcription = CYCLOSPORINE

4) antibodies that bind to IL-2 receptor and are used in renal transplantation = BASILIXIMAB, DACLIZUMAB

5) converted to an active metabolite and inhibits inosine monophosphate dehydrogenase = MYCOPHENOLATE MOFETIL

6) binds to TNF and used to treat rheumatoid arthritis = ADALIMUMAB, ETANERCEPT, INFLIXIMAB

7) prevents Rh hemolytic disease of the newborn = Rh (D) IMMUNE GLOBULIN

8) binds FKBP and inhibits calcineurin's dephosphorylation of NFAT, leading to the blockade of IL-2 transcription = TACROLIMUS

9) inhibit synthesis of leukotrienes and prostaglandins, as well as decreasing synthesis of interleukins and cytokines = CORTICOSTEROIDS (prednisone)

1) diarrhea, vomiting, leukopenia = MYCOPHENOLATE MOFETIL

2) renal dysfunction, hypertension, neurotoxicity = CYCLOSPORINE, TACROLIMUS

3) teratogenic effects, peripheral neuropathy, venous thromboembolic events = THALIDOMIDE

4) renal dysfunction, hypertension, hirsutism, gingival hyperplasia = CYCLOSPORINE

5) hyperlipidemia, myelosuppression = SIROLIMUS

FALSE

True statement:
Cyclosporine is eliminated primarily by the LIVER and one of its major adverse effects is renal dysfunction.