B. 30- immunopharmacology 2. inhibitors of cytokine gene expression, 5-ASA derivatives

Question 1

examples for 5-Aminosalicylate (5-ASA)

Answer 1

mesalazine

sulfasalzine

Question 2

what is the mechanism of 5-Aminosalicylate (5-ASA): sulfasalzine

Answer 2

PPARᵧ agonist–> ↓ NFᴋB, TLR’S
↓ cytokine expression
COX & LOX inhibition
antioxidant role

Question 3

how is 5-ASA’S given?

Answer 3

oral, parenteral (suppository)

Question 4

what are the indications for 5-ASA’s? (sulfasalazine)

Answer 4

autoimmune diseaes

IBD: UC&raquo_space;CD

Question 5

SE of sulfasalazine?

Answer 5

nausea
vomiting
headache
rash

Question 6

characteristic of sulfasalazine and mesalazine

Answer 6

prodrug converted by colon bacteria into 5-ASA

Question 7

what are chloroquine and hydroxychloroquine ?

Answer 7

anti-malarial drugs

Question 8

mechanism of chloroquine and hydroxychloroquine

Answer 8

interfere with macrophages lysosomal pH–> inhibit antigen catabolism and presentation

Question 9

how is chloroquine and thalidomide given?

Answer 9

oral

Question 10

when is chloroquine given?

Answer 10

autoimmune diseases (RA, SLE)

Question 11

SE of chloroquine and hydroxychloroquine

Answer 11

skin exanthema
GI irritation
ocular damage
hemolysis in patients with G6PD

Question 12

does chloroquine have a long or short T1/2?

Answer 12

long

Question 13

mechanism of thalidomide

Answer 13

suppression of TNF-𝝰, ↑ IL-10,
↓ neutrophil phagocytosis
altered adhesion molecule expression
↑ cell-mediated immunity

Question 14

when do we give thalidomide?

Answer 14

autoimmune diseases (SLE) 
solid tumors

Question 15

SE from thalidomide

Answer 15

peripheral neuropathy
neutropenia
teratogenic

Question 16

for what is Glatiramer acetate given?

Answer 16

multiple sclerosis

Question 17

how is glatiramer acetate given?

Answer 17

parenteral

Question 18

SE of glatiramer acetate

Answer 18

injection site reaction

Question 19

what does glatiramer acetate consist of?

Answer 19

a mixture of synthetic polypeptides and 4 amino acids

Question 20

what are calcineurin inhibitors?

Answer 20

calcium and calmodulin-dependent serine/ threonine protein phosphatase
*plays a role in the activation of T cells

Question 21

give 2 calcineurin inhibitors

Answer 21

cyclosporine

tacrolimus (FK506)

Question 22

how are cyclosporine and tacrolimus given?

Answer 22

oral or parenteral

Question 23

major side effect of both cyclosporine and tacrolimus?

Answer 23

nephrotoxicity

Question 24

mechanism of cyclosporine

Answer 24

binds to cyclophilin–> inhibits calcineurin–> alters activation of T cell transcription factors–> IL-2, IL-3, IFN-ᵧ ↓

Question 25

mechanism of tacrolimus

Answer 25

binds to FK-binding protein--> inhibits calcineurin--> alters activation of T cell transcription factors--> IL-2, IL-3, IFN-ᵧ ↓

Question 26

1st line agent for bone marrow transplantation

Answer 26

cyclosporine

Question 27

what do cyclosporine and tacrolimus eventually do?

Answer 27

IL-2, IL-3, IFN-ᵧ ↓

Question 28

indications for cyclosporine

Answer 28

bone marrow transplantation (1st line agent) solid-organ transplantation autoimmune diseases ( RA, psoriasis, uveitis)

Question 29

indications for tacrolimus

Answer 29

``` solid-organ transplantation autoimmune diseases atopic dermatitis (topical) ```

Question 30

type of metabolism in cyclosporine and sirolimus

Answer 30

hepatic P450 metabolism

Question 31

does cyclosporine have long or short T1/2?

Answer 31

long

Question 32

side effects of cyclosporine

Answer 32

nephrotoxicity hepatotoxicity hypertension gingival hypertrophy

Question 33

what is sirolimus (rapamycin)?

Answer 33

mTOR inhibitor

Question 34

what is an mTOR inhibitor?

Answer 34

inhibits mTOR which is a key regulator of an intracellular signaling pathway, involved in cell growth, proliferation angiogenesis, metabolism

Question 35

mechanism of sirolimus

Answer 35

binds to FK-binding protein--> inhibits the kinase activity of mTOR

Question 36

how is sirolimus given?

Answer 36

oral or parenteral

Question 37

what is the T1/2 of sirolimus?

Answer 37

up to 60 h'

Question 38

indications of sirolimus

Answer 38

neuroendocrine tumors breast and renal cancer solid-organ transplantation sirolimus-eluting stents to prevent restenosis after coronary angioplasty

Question 39

side effects of sirolimus

Answer 39

myelosupression hepatotoxicity pneumonitis

Question 40

what is Tofacitinib?

Answer 40

inhibitor of JAK1 and JAK3

Question 41

how is tofacitinib given?

Answer 41

orally

Question 42

indications for tofacitinib

Answer 42

``` autoimmune disease (RA, IBD, ankylosing spondylitis) monotherapy or in combination with methotrexate ```

Question 43

side effects of tofacitinib

Answer 43

"Hil": hyperlipidemia infections elevated liver enzymes

Question 44

what is a JAK inhibitor

Answer 44

JAK is an intracellular tyrosine kinase--> JAK-STAT pathway that transmits cytokine-mediated signals