B. 30- immunopharmacology 2. inhibitors of cytokine gene expression, 5-ASA derivatives Flashcards
examples for 5-Aminosalicylate (5-ASA)
mesalazine
sulfasalzine
what is the mechanism of 5-Aminosalicylate (5-ASA): sulfasalzine
PPARᵧ agonist–> ↓ NFᴋB, TLR’S
↓ cytokine expression
COX & LOX inhibition
antioxidant role
how is 5-ASA’S given?
oral, parenteral (suppository)
what are the indications for 5-ASA’s? (sulfasalazine)
autoimmune diseaes
IBD: UC»_space;CD
SE of sulfasalazine?
nausea
vomiting
headache
rash
characteristic of sulfasalazine and mesalazine
prodrug converted by colon bacteria into 5-ASA
what are chloroquine and hydroxychloroquine ?
anti-malarial drugs
mechanism of chloroquine and hydroxychloroquine
interfere with macrophages lysosomal pH–> inhibit antigen catabolism and presentation
how is chloroquine and thalidomide given?
oral
when is chloroquine given?
autoimmune diseases (RA, SLE)
SE of chloroquine and hydroxychloroquine
skin exanthema
GI irritation
ocular damage
hemolysis in patients with G6PD
does chloroquine have a long or short T1/2?
long
mechanism of thalidomide
suppression of TNF-𝝰, ↑ IL-10,
↓ neutrophil phagocytosis
altered adhesion molecule expression
↑ cell-mediated immunity
when do we give thalidomide?
autoimmune diseases (SLE) solid tumors
SE from thalidomide
peripheral neuropathy
neutropenia
teratogenic
for what is Glatiramer acetate given?
multiple sclerosis
how is glatiramer acetate given?
parenteral
SE of glatiramer acetate
injection site reaction
what does glatiramer acetate consist of?
a mixture of synthetic polypeptides and 4 amino acids
what are calcineurin inhibitors?
calcium and calmodulin-dependent serine/ threonine protein phosphatase
*plays a role in the activation of T cells
give 2 calcineurin inhibitors
cyclosporine
tacrolimus (FK506)
how are cyclosporine and tacrolimus given?
oral or parenteral
major side effect of both cyclosporine and tacrolimus?
nephrotoxicity
mechanism of cyclosporine
binds to cyclophilin–> inhibits calcineurin–> alters activation of T cell transcription factors–> IL-2, IL-3, IFN-ᵧ ↓
mechanism of tacrolimus
binds to FK-binding protein–> inhibits calcineurin–> alters activation of T cell transcription factors–> IL-2, IL-3, IFN-ᵧ ↓
1st line agent for bone marrow transplantation
cyclosporine
what do cyclosporine and tacrolimus eventually do?
IL-2, IL-3, IFN-ᵧ ↓
indications for cyclosporine
bone marrow transplantation (1st line agent)
solid-organ transplantation
autoimmune diseases ( RA, psoriasis, uveitis)
indications for tacrolimus
solid-organ transplantation autoimmune diseases atopic dermatitis (topical)
type of metabolism in cyclosporine and sirolimus
hepatic P450 metabolism
does cyclosporine have long or short T1/2?
long
side effects of cyclosporine
nephrotoxicity
hepatotoxicity
hypertension
gingival hypertrophy
what is sirolimus (rapamycin)?
mTOR inhibitor
what is an mTOR inhibitor?
inhibits mTOR which is a key regulator of an intracellular signaling pathway, involved in cell growth, proliferation angiogenesis, metabolism
mechanism of sirolimus
binds to FK-binding protein–> inhibits the kinase activity of mTOR
how is sirolimus given?
oral or parenteral
what is the T1/2 of sirolimus?
up to 60 h’
indications of sirolimus
neuroendocrine tumors
breast and renal cancer
solid-organ transplantation
sirolimus-eluting stents to prevent restenosis after coronary angioplasty
side effects of sirolimus
myelosupression
hepatotoxicity
pneumonitis
what is Tofacitinib?
inhibitor of JAK1 and JAK3
how is tofacitinib given?
orally
indications for tofacitinib
autoimmune disease (RA, IBD, ankylosing spondylitis) monotherapy or in combination with methotrexate
side effects of tofacitinib
“Hil”:
hyperlipidemia
infections
elevated liver enzymes
what is a JAK inhibitor
JAK is an intracellular tyrosine kinase–> JAK-STAT pathway that transmits cytokine-mediated signals
