Immuno - Immunosuppressants (Immunosuppressants & their targets)

Question 1

What are immunosuppressants, and how do they function?

Answer 1

Agents that block lymphocyte activation and proliferation.

Question 2

What effect do immunosuppressants have on acute transplant rejection, and how?

Answer 2

Reduce acute transplant rejection by suppressing cellular immunity.

Question 3

How are immunosuppressants frequently used in a given regimen, and why?

Answer 3

Frequently combined to achieve greater efficacy with decreased toxicity.

Question 4

What are 2 major risks posed by chronic suppression?

Answer 4

Chronic suppression increases risk of infection and malignancy

Question 5

Give 6 examples of immunosuppressants.

Answer 5

(1) Cyclosporine (2) Tacrolimus (3) Sirolimus (Rapamycin) (4) Basiliximab (5) Azathioprine (6) Glucocorticoids

Question 6

What kind of drug is cyclosporine? What does it bind? What effect does this have, and via what mechanism?

Answer 6

Immunosuppressant, Calcineurin inhibitor; Binds Cyclophilin; Blocks T cell activation by PREVENTING IL-2 TRANSCRIPTION

Question 7

What kind of drug is tacrolimus? What does it bind? What effect does this have, and via what mechanism?

Answer 7

Immunosuppressant, Calcineurin inhibitor; Binds FK506 binding protein (FKBP); Blocks T cell activation by PREVENTING IL-2 TRANSCRIPTION

Question 8

What is another name for Sirolimus? What kind of drug is it? What does it bind? What effect does this have, and via what mechanism?

Answer 8

Sirolimus (Rapamycin); Immunosuppressant, mTOR inhibitor; Binds FKBP; Blocks T cell activation and B cell differentiation by PREVENTING IL-2 SIGNAL TRANSDUCTION

Question 9

What kind of drug is basiliximab? What is its mechanism?

Answer 9

Immunosuppressant, Monoclonal antibody; blocks IL-2R

Question 10

What is azathioprine? What effect does this have, and via what mechanism?

Answer 10

Immunosuppressant, Antimetabolite precursor of 6-mercaptopurine; Inhibits lymphocyte proliferation by blocking nucleotide synthesis; Think: “Azathio-purine”

Question 11

By what mechanism do glucocorticoids act, and what effect does this have?

Answer 11

Inhibit NF-kappaB; Suppress both B and T cell function by decreased transcription of many cytokines

Question 12

What are 3 uses for Cyclosporine?

Answer 12

(1) Transplant rejection prophylaxis (2) Psoriasis (3) Rheumatoid arthritis

Question 13

What is a use for Tacrolimus?

Answer 13

Transplant rejection prophylaxis

Question 14

What is a use for Sirolimus (Rapamycin)?

Answer 14

Kidney transplant rejection prophylaxis

Question 15

What is a use for Basiliximab?

Answer 15

Kidney transplant rejection prophylaxis

Question 16

What are 5 uses for Azathioprine?

Answer 16

(1) Transplant rejection prophylaxis (2) Rheumatoid arthritis (3) Crohn disease (4) Glomerulonephritis (5) Other autoimmune conditions

Question 17

What are 3 uses for Glucocorticoids?

Answer 17

(1) Transplant rejection prophylaxis (immune suppression) (2) Many autoimmune disorders (3) Inflammation

Question 18

What are 4 immunosuppressants used for any transplant prophylaxis? What are 2 immunosuppressants used for kidney transplant rejection prophylaxis?

Answer 18

(1) Cyclosporine (2) Tacrolimus (3) Azathioprine (4) Glucocorticoids; (1) Sirolimus (Rapamycin) (2) Basiliximab

Question 19

What are 7 toxicities associated with Cyclosporine?

Answer 19

(1) Nephrotoxicity (2) Hypertension (3) Hyperlipidemia (4) Hyperglycemia (5) Tremor (6) Hirsuitism (7) Gingivial hyperplasia

Question 20

To which other immunosuppressant is Tacrolimus similar in terms of toxicities? Again, what are the 7 toxicities associated with this other immunosuppressant? What are 4 ways in which Tacrolimus toxicities are different?

Answer 20

Similar to cyclosporine; (1) Nephrotoxicity (2) Hypertension (3) Hyperlipidemia (4) Hyperglycemia (5) Tremor (6) Hirsuitism (7) Gingivial hyperplasia; No gingivial hyperplasia or hirsuitism; Increased risk of diabetes and neurotoxicity

Question 21

What are 5 toxicities associated with Sirolimus (Rapamycin)? What is an important toxicity that Sirolimus does NOT have?

Answer 21

(1) Anemia (2) Thrombocytopenia (3) Leukopenia (4) Insulin resistance (5) Hyperlipidemia; Non-nephrotoxic; Think: “Kidney ‘SIR-vives’”

Question 22

What are 3 toxicities associated with Basiliximab?

Answer 22

(1) Edema (2) Hypertension (3) Tremor

Question 23

What are 3 toxicities associated with Azathioprine?

Answer 23

(1) Leukopenia (2) Anemia (3) Thrombocytopenia

Question 24

What are 9 toxicities associated with Glucocorticoids?

Answer 24

(1) Hyperglycemia (2) Osteoporosis (3) Central obesity (4) Muscle breakdown (5) Psychosis (6) Acne (7) Hypertension (8) Cataracts (9) Peptic ulcers

Question 25

What are the 2 calcineurin inhibitor immunosuppressants? What is the most significant toxicity to associate with both of them?

Answer 25

Calcineurin inhibitors: Cyclosporine & Tacrolimus; Both calcineurin inhibitors are highly nephrotoxic

Question 26

What 2 drugs bind FKBP?

Answer 26

Bind FKBP: Tacrolimus & Sirolimus (Rapamycin); -limus drugs bind FKBP

Question 27

With what other drug is Sirolimus synergistic?

Answer 27

Synergistic with cyclosporine

Question 28

In what procedure is Sirolimus used?

Answer 28

Also used in drug-eluting stents

Question 29

What degrades 6-MP? To which immunosuppressant is this relevant, and why?

Answer 29

6-MP degraded by xanthine oxidase; Azathioprine; Antimetabolite precursor of 6-mercaptopurine

Question 30

What increases toxicity of Azathiopurine?

Answer 30

Toxicity increased by allopurinol

Question 31

Aside from its associated toxicities, what syndrome can Glucorticoids cause?

Answer 31

Can cause iatrogenic Cushing syndrome

Question 32

Draw a T helper cell depicting the following immunosuppressants and their targets: (1) Azathioprine (2) Basiliximab (3) Corticoisteroids (4) Cyslosporine (5) Sirolimus (Rapamycin) (6) Tacrolimus.

Answer 32

See p. 216 in First Aid for visual at top.