Drugs used in Organ Transplantation

Question 1

What is the mechanism of glucocorticoids (Prednisone, prednisolone_?

Answer 1

Suppress distribution and reactivity of lymphoid and myloid cells, catabolic actions at GRE

Question 2

What is the clinical use of glucocorticoids (Prednisone, prednisolone?

Answer 2

Acute use and emergency adjuncts to other suppressants

Question 3

What are the toxicities of glucocorticoids (Prednisone, prednisolone)?

Answer 3

Catabolic state, hypertension, diabetogenic, avascular necrosis, osteopenia

Question 4

What is the mechanism of Antithymocyte Globulin (ALG) and Antilymphocyte Globulin (ATG)?

Answer 4

Polyclonal suppression of thymocytes (T) or lymphocytes (T&B, NK), Allows early temp withdrawal of drug

Question 5

Whats the clinical use of Antithymocyte Globulin (ALG) and Antilymphocyte Globulin (ATG)?

Answer 5

Induction, initial or steroid resistant rejection, GVH rxns

Question 6

What are the toxicities of Antithymocyte Globulin (ALG) and Antilymphocyte Globulin (ATG)?

Answer 6

Fever, chills, hypotension, SERUM SICKNESS (type III), sensitization

Question 7

What is the mechanism of Muromonab-CD3 (OKT-3)

Answer 7

MAB (monoclonal antibody) against the T-cell receptor

Question 8

What is the clinical use of Muromonab-CD3 (OKT-3)

Answer 8

Induction, initial or steroid resistant rejection

Question 9

What is the toxicities of Muromonab-CD3 (OKT-3)

Answer 9

‘Cytokine release’ syndrome so systemic shock (pretreat with steroid), infusion rxns,sensitization

Question 10

What is the mechanism of Alemtuzumab

Answer 10

hMAB (monoclonal antibodies) against CD52 on lymphocytes monocytes macrophages NK leading to prolonged T&B depletion

Question 11

What is the clinical use of Alemtuzumab

Answer 11

Induction, initial or steroid resistant rejection (same as OKT-3)

Question 12

What treatments is Alemtuzumab used for?

Answer 12

Chronic lymphocytic leukemia (CLL) and transplants

Question 13

What is the mechanism of Daclizumab and Basiliximab

Answer 13

Humanized and chimeric MAB (monoclonal antibodies) against IL2 receptor on T-cells. So when IL-2R is more active it becomes more selective

Question 14

What is the clinical use of Daclizumab and Basiliximab

Answer 14

Acute renal rejection

Question 15

What are the toxicities of Daclizumab and Basiliximab

Answer 15

Infusion rxns, tremor, headache, dypsnea, hypertension

Question 16

What is the mechanism of Abatacept and Belatacept

Answer 16

Fusion of Fc of IgG1 and CTLA-4 binds to CD80,86 preventing second signal in T-cells, blocking activation

Question 17

What is the clinical use of Abatacept and Belatacept

Answer 17

Used for rheumatoid arthritis, but allows temporary removal of more toxic agents in slow graft response or rejection

Question 18

What are the toxicities of Abatacept and Belatacept

Answer 18

Infusion rxs, hypersenitivity, nasopharyngitis, URI, nausea, headache

Question 19

What is the mechanism of Thalidomide?

Answer 19

Stimulates and changes specificity of T-cells, supresses B cells stimulates T cells but in a immunomodulatory fasion such as changes in immune reactivity and specificity. Used in combo for allogenic bone marrow transplantation.

Question 20

What is the clinical use of Thalidomide?

Answer 20

Malignancy, GVHR

Question 21

What are the toxicities of Thalidomide?

Answer 21

Teratogenic, peripheral neurotoxicity

Question 22

What is the mechanism of Calcineurin inhibitors: Cyclosporine (CSA and Tacrolimus (FK-506)?

Answer 22

Calcineurin (phosphatase PP2b) inhibitor blocking signal transduction activating T-cells

Question 23

What is the clinical use of Calcineurin inhibitors: Cyclosporine (CSA and Tacrolimus (FK-506)?

Answer 23

Primary agents used in organ transplantation of all kinds in combo with antimetabolites. CSA binds to cyclophilin and FK506 binds to tacrolimus

Question 24

What is the toxicities of Calcineurin inhibitors: Cyclosporine (CSA and Tacrolimus (FK-506)?

Answer 24

Nephrotoxicity is limiting, neurotoxic, hypertension, hyperlipidemia, gum hyperplasia (CSA), diabetes (FK-506). Watch for drug interactions with CYP450s

Question 25

What is the mechanism of Antiproliferative agents: Sirolimus (rapamycin), Everolimus?

Answer 25

inhib mTOR kinase, prevents CDK2 phosphorylation and so blocks cell cycle progression in T-cells. Binds to FK506BP12

Question 26

What is the clinical use of Antiproliferative agents: Sirolimus (rapamycin), Everolimus?

Answer 26

Used in organ transplants of all kinds, not used in combo of calcineurin inhibs but as alternate primary drugs with antimetabolites

Question 27

What are the Toxicities of Antiproliferative agents: Sirolimus (rapamycin), Everolimus?

Answer 27

Hyperlipidemia, Myelosupression esp thrombocytopenia, also anemia, delayed wound healing and used in vascualr stents watch with interaction at CYP450s

Question 28

What is the mechanism of Antimetabolites: Mycophenolate and Mofetil?

Answer 28

Prodrug of mycophenolic acid and inhib of T&B cell inosine monophosphate dehydrogenase in the purine pathway for GMP synthesis. T and B cells are highly dependent on de novo purine synthesis hence are suppressed

Question 29

What is the clinical use of Antimetabolites: Mycophenolate and Mofetil?

Answer 29

Used in secondary ancillary immunosuppressant drug combo with Calcineurin inhibs or Antiproliferative agents

Question 30

What are the toxicities of Antimetabolites: Mycophenolate and Mofetil?

Answer 30

Leukopenia, diarrhea, nausea, vomiting, infection

Question 31

What is the mechanism of Antimetabolites: Azathioprine?

Answer 31

Prodrug of 6-MP, an inhib of ATP and GTP synthesis. Can be genetic deficiencies in metabolism by thiopurine methyltransferase

Question 32

What is the clinical use of Antimetabolites: Azathioprine?

Answer 32

Largely replaced by mycophenolate but is alt. Dose reduced with allopurinol

Question 33

What are the toxicities of Antimetabolites: Azathioprine?

Answer 33

Bone marrow suppression, hepatotoxicity, GI toxicity, pancreatitis, alopecia