Tuesday 3 - memorize these sheets ILT Immunosuppressives

Question 1

mineralocorticoids vs glucocorticoids

Answer 1

glucocorticoid - carbohydrate metabolism regulating - main one in humans is hydrocortisone - PROTOTYPE COMPOUND is CORTISOL - REACTS ON GLUCOCORTICOID RESPONSE ELEMENTS IN DNA TO REGULATE Tx

-Sodium retention
+liver gycogen deposition
+anti inflammatory

mineralocorticoid - electrolyte balance regulating - main one in humans is aldosterone

+Sodium retention

• liver gycogen deposition
• anti inflammatory

Both secreted by the adrenal glands in response to ACTH (adrenocorticotropic hormone)

Question 2

The most widely used immunosuppresant

Answer 2

prednisone

Question 3

Steroid effects of the immune system

Answer 3

^ in cerculating neutrophils
lymphopenia
decreased peripheral monocytes, eosinophils

Question 4

steroid effects on inflammatory mediators

Answer 4

decreased COX 2 expression
inhibits arachadonic acid
inhibit degranulation of granulocytes
inhibit synth of TNF, IL-1,2, and INF

Question 5

Two calcineurin inhibitors

similarities and differences

what are they used to treat

Answer 5

Cyclosporine - binds cyclophilin, inhibits calcineurin, blocks dephosphorylation events needed for cytokine and t cell activation. Long term therapy for transplants. Renal, nephro toxic

Tacrolimus - binds FKBP, inhibits calcineurin. 100 times more potent than cyclosporine. similar tox. THIS DOES NOT STOP THE PROLIFERATION OF T CELLS LIKE SIROLIMUS DOES

BOTH INHIBIT PHOSPHATASE ACTIVITY

used to treat organ donation rejection or severe autoimmune disease (like RA)

Question 6

ANTIPROLIFERATIVE/ANTIMETABOLIC DRUGS

similarities and differences

what are they used for

Answer 6

Sirolimus (rapamycin) - Binds FKBP and inhibits mTOR (mamalian kinase target of rapamycin). blocks G1 to s progression OF T CELLS!!!!!!!!!! SE: increase in fats, cholesterol. nephrotox, lymphomas, infection, substrate of CYP3A4

Mycophenolate Mofetil - a metabolite of this inhibits inosine monophosphate dehydrogenase, which makes guanine. SE: hematologic and gastro tox. leukopenia, diarrhea, emesis.

Used to stop rejection of transplanted organs - prevent clonal expansion of both B and T lymphocytes

Question 7

anti-thymocyte globulin (ATG)

Answer 7

purified antibodies taken from animals immunized against human thymocytes (hematopoietic progenitor cells present in the thymus)

Question 8

Muromonab

Answer 8

Prevents rejection of kidney, liver, heart transplants. Mouse monoclonal antibody binds epsilon chain of CD3 (T CELL RECEPTOR COMPLEX). BLOCKS ANTIGEN RECOGNITION. initial interaction cause cytokine release from t cells: mild flu Sx to high shock. give glucocorticoids first. cannot use multiple times.

Question 9

Daclizumab or Basiliximab

Answer 9

Anti IL-2 RECEPTOR (!!!!!!) (CD25). For organ transplant. binds IL-2 on activated but not restion t cells

Question 10

Glucocorticoids

mech

Answer 10

Glucocorticoid response elements in DNA

regulate gene transcription

Question 11

Muromonab

mech

Answer 11

acts on T-cell receptor complex (blocks antigen recognition)

Question 12

Cyclosporine

mech

Answer 12

Inhibits calcineurin (inhibits phosphatase activity)- once this is stopped, this NUCLEAR activator of t cells doesn’t get phosphorylated, then that means the t cell doesn’t get activated.

Question 13

Tacrolimus

mech

Answer 13

Inhibits calcineurin (inhibits phosphatase activity)- once this is stopped, this NUCLEAR activator of t cells doesn’t get phosphorylated, then that means the t cell doesn’t get activated. (this DOESN’T STOP THE PROLIFERATION OF T CELLS, THAT IS SIROLIMUS)

Question 14

Mycophenolate mofetil

mech

Answer 14

inhibits Inosine monophosphate dehydrogenase - get a decrease in the production of guanine

Question 15

Sirolimus

mech

Answer 15

(mTOR) (inhibits activity) – interacts with FK binding protein, but stops prolifeoration of t cells. tacrolimus acts differently. that’s why you may combine them