Tansplant Drugs

Question 1

Classes of immunosuppressives

Answer 1

Glucocorticoids, cyototoxic antimetabolites, calcineurin and mTOR inhibitors, anti-cytokine/cytokine receptor Ab’s, Anti T and B cell therapy, costimulation pathway inhibitors

Question 2

Allograft Immune response

Answer 2

Antigens from transplanted organ are presented to host T-Cells

Question 3

TNF-alpha

Answer 3

produced by helper T Cells, macrophages, NK cells

Question 4

Glucocorticoid mechanism of action

Answer 4

Inhibit expression of pro-inflammatory mediators

Question 5

Cytotoxic antimetabolite mechanism of action

Answer 5

Inhibit clonal expansion of lymphocyte population

Question 6

Calcineurin and mTOR inhibitors mechanism of action

Answer 6

Inhibit lymphocyte signalling

Question 7

IL2 receptor Ab’s mechanism of action

Answer 7

Neutralize cytokines and cytokine receptors

Question 8

T cell depletor mechanism of action

Answer 8

Depletes T Cells (no shit)

Question 9

Belatacept mechanism of action

Answer 9

Blockade of costimulation

Question 10

Glucocorticoid uses

Answer 10

Graft vs host, RA, SLE, asthma, MS, allergic reactions, BLOCKS CYTOKINE STORM CAUSED BY MUROMANAD-CD3

Question 11

Glucocorticoid toxicity

Answer 11

Growth suppression, avascular bone necrosis, osteopenia, risk of infection, cataracts, impaired healing, hyperglycemia, htn, DIABETEOGENIC WHEN COMBINED WITH CALCINEURIN INHIBITORS

Question 12

Azathioprine mechanism of action

Answer 12

Purine antimetabolite, inhibits DNA, RNA synthesis

Question 13

Azathioprine adverse effects

Answer 13

Immunosuppression, myelosuppression, toxicity in GI mucosa, bone marrow due to suppression of proliferating cells

Question 14

Azathioprine pharmacology

Answer 14

Azathioprine is cleaved into 6-mercatopurine in liver, RBC’s, taken up by lymphocytes, converted into 6-thio-GTP and 6-thio-dGTP, which are incorporated into RNA, DNA

Question 15

Azathioprine disposition

Answer 15

PO, well absorbed, hepatic, RBC metabolism, renal excretion

Question 16

Azathioprine DDI’s

Answer 16

Decrease dose with allopurinol, exacerbation of myelosuppression with ACE inhibitors because they decrease EPO.

Question 17

Mycophenolate Mofetil Mechanism of action

Answer 17

Inhibits IMP dehydrogenase, an important part of the guanine biosynthesis pathway. Selectively targets B and T cells, which depend on de novo purine sythesis.

Question 18

Mycophenolate Mofetil pharmacology

Answer 18

Hydrolized in liver to active metabolite - mycophenolic acid

Question 19

Mycophenolate Mofetil use

Answer 19

Prevent rejection of kidney transplants, used with calcinuerin inhibitors and glucocorticoids, and in autoimmune disease.

Question 20

Mycophenolate Mofetil ADME

Answer 20

Metabolized to glucoronide derivative in liver, excreted in urine

Question 21

Mycophenolate Mofetil DDI’s

Answer 21

Tacrolinus impairs glucoronidation, decrease dose. Plasma levels elevated in renal insufficiency

Question 22

Mycophenolate Mofetil Toxicity

Answer 22

Luekopenia, Diarrhea, vomiting, teratogenic,

Question 23

Cyclosporine, Tacrolimus mechanism of action

Answer 23

Calcinuerin Inhibitors - IL-2 production inhibition

Question 24

IL-2

Answer 24

Promotes clonal expansion, activation, and differentiation of mature T-Cells

Question 25

Calcinuerin

Answer 25

Calcinuerin is induced as a consequence of T-Cell receptor activation, and promotes T-Cell expansion and differentiation by intracellular signalling

Question 26

Sirolimus mechanism of action

Answer 26

Prevents T-cell activation and proliferation by inhibiting protein synthesis

Question 27

Cyclosporine uses

Answer 27

Transplant rejection prevention, RA, psoriasis in immunocompromised, IBD, endogenous uveitis, nephrotic syndrome

Question 28

Cyclosporine ADME

Answer 28

PO/IV (different PO preparatations are NOT interchangeable), CYP3A, >25 metobolites, excreted in feces

Question 29

Cyclosporine Toxicity

Answer 29

Renal Dysfunction, HTN - common in renal and universal in cardiac transplants, diabetogenic with glucocorticoids

Question 30

Cyclosporine DDI's

Answer 30

CYP3A inhibition or induction has a major effect - monitor blood levels. Renal dysfunction when combined with NSAIDS or sirolimus

Question 31

Tacrolimus ADME

Answer 31

PO/IV - must be individually dosed to patient. Variable/incomplete GI absorbtion. Extensive CYP3A Metabolism, fecal excretion

Question 32

Tacrolimus toxicity

Answer 32

Nephrotoxic, htn, diabetogenic, especially w/glucocorticoids

Question 33

Tacrolimus DDI's

Answer 33

CYP3A inhibition or induction has a major effect - monitor blood levels. Renal dysfunction when combined with NSAIDS- MONITOR BLOOD LEVELS

Question 34

Sirolimus mechanism of action

Answer 34

binds to and inhibitos mTOR, a kinase that is key in cell cycle progression at G1-S. DOES NOT INHIBIT CALCINEURIN. Inhibits T-Cell activation and proliferation

Question 35

Sirolimus ADME

Answer 35

PO, CYP3A - highly variable bioavailability, monitor blood levels (consistently with or without food.) Fecal excretion. T 1/2 62 hours

Question 36

Sirolimus toxicity

Answer 36

Not renal toxic. Dose dependent htn, increase in serum cholesterol, triglycerides, lymphocoele, myelosupression,

Question 37

Sirolimus DDI's

Answer 37

CYP3A inhibition or induction has a major effect - monitor blood levels. Aggravates renal toxicity WITH CYCLOSPORINE.