Al-Mehdi: Rx of IBD Flashcards
pathogenesis behind IBD summed up
loss of tolerance of mucosal immune system leading to attack of one’s own microbiota
how are naiive Th0 (CD4) T cells activated
dendritic cells present antigen
co-stimulation from CD80/86 binding to CD28
activation of T cell allows for what to be produced and what effect
IL-2; clonal expansion of T cells
normally, _____ takes off phosphate group of NFAT when influx of Ca2+ binds to calmodulin in T cell
calcineurin
what happens when IL-2 autocrine signaling happens in T cell
activates mTOR, cytokines produced, clonal expansion of cells
cytokine that activates Th1 cell
IL-12
T cell that activates macrophages and CD8+ T cells
Th1
cytokines that activate Th17 T cell
IL-1, 6, 23
this T cell attracts neutrophils to infection site
Th17
T cells involved in Crohn’s disease
Th1 and Th17
cytokines that activate Th2 T cell
IL-4, IL-25
cytokine that Th2 cell makes that activates eosinophils
IL-5
cytokine that Th2 cell makes that activates mast cells
IL-9
cytokines from Th2 T cell involved in elimination of helminths, atopy, eosinophilic esophagitis
IL-5 and IL-9
T cell involved in Ulcerative colitis
Th2
cytokine that activates Treg cell
IFN-a
T cell that produces IL-10 and TGF-b to prevent autoimmune disease and inflammation
Treg
cytokines that activate Tfh (T follicular helper cell)
IL-4, IL-21
T cell that produces IL-21 that activates B cells
Tfh (T follicular helper) cell
Which T cell and which cytokines reduce inflammation and disease severity in autoimmune diseases?
Treg; IL-10 and TGF-beta
drugs that block lymphocyte egress from lymph nodes and peyer’s patches (used for UC)
OZANIMOD
FINGOLIMOD
(-IMODs)
these drugs are irreversible agonists of sphingosine-1-phosphate receptor (block lymphocyte egress)
OZANIMOD
FINGOLIMOD
drugs used for UC and CD that block lymphocyte transmigration out of endothelium and their MoA
VEDOLIZUMAB
ETROLIZUMAB
(-LIZUMABs)
MoA: anti-a4b7 in the gut
integrin on lymphocyte that VEDOLIZUMAB and ETROLIZUMAB block
a4b7
on EC of gut that a4b7 bind to
MAdCAM
anti-a4b7 and anti-a4b1 MoA (blocks lymphocyte transmigration out of endothelium)
NATALIZUMAB
drug that can cause progressive multifocal leukoencephalopathy (PML) due to binding of a4b1 that is found on EC everywhere in body
NATALIZUMAB
used for CD and MS that has SE of PML
NATALIZUMAB
drugs that block mucosal cytokine release and used for UC
SULFASALAZINE
MESALAMINE
OLSALAZINE
BALSALAZIDE
drugs used for UC that have anti-inflammatory effect and block mucosal cytokine release
MESALAMINE
OLSALAZINE
BALSALAZIDE
SULFASALAZINE
What 2 components make up SULFASALAZINE
sulfapyridine
5-ASA
component of SULFASALAZINE that has all the side effects
sulfapyridine
enzyme produced by bacteria that cleaves N=N bond of sulfasalazine (splitting up 5-ASA and sulfapyridine)
azoreductase
2 different actions of glucocorticoids that are used for IBD
anti-inflammatory
immunosuppressant—–genomic (block inflammatory gene expression)
glucocorticoids used in CD and UC
BUDESONIDE
PREDNISONE
METHYLPRENISOLONE
preferred glucocorticoid to use in IBD due to its metabolism by CYP34A so less SE’s
BUDESONIDE
SE’s of this type of drug include:
neuropsychiatric (mood)
cosmetic (acne, hair loss)
metabolic (bone loss)
infectious
glucocorticoids
chemoattractants for leukocytes to sites of infection/inflammation
IL-17
IL-22
IL-8
CXCL8
cytokine produced from activated macrophages that induces acute-phase protein production by the liver (CRP)
IL-6
2 anti-TNF drugs used to treat CD and UC
INFLIXIMAB
ADALIMUMAB
anti-TNF drug used in CD that is safe in pregnancy
CERTOLIZUMAB pegot
anti-TNF drug used only in UC
GOLIMUMAB
adverse effects of immunosuppressant therapy
infection
Why do you do a PPD test before starting anti-TNF type biologics?
reactivation of TB
Why do patients need to obstain from alcohol during Rx with metronidazole?
inhibits aldehyde dehydrogenase (enzyme used by the liver to further break down alcohol) and causes flushing
MoA of Metronidazole
produces free radicals that damage bacterial DNA
inhibitors of purine de novo synthesis (used for both CD and UC)
6-MP
Azathioprine
Activation of Ebstein-Barr Virus
Pancreatitis
Hepatitis
LEUKOPENIA
SE’s of 6-MP and AZA
Co-administration of which drugs or mutation of which gene will cause leukopenia in a patient on 6-MP/AZA?
6-MP/AZA + Allopurinol/febuxostat
TPMT mutation
_____ blocks xanthine oxidase (which makes 6-MP inactive); so if you use 6-MP + ____= toxicity
Allopurinol
blocks phosphatase (removal of phosphate group from NFAT); calcineurin inhibitor
Cyclosporine (for UC)
Tacrolimus
blocks mTOR pathway
Sirolimus
Iron metabolism (ferroportin)
Neurotransmitter synthesis (dopamine hydroxylase)
Melanin synthesis (dopamine hydroxylase)
Energy production (cytochrome c oxidase)
Synthesis and cross-linking of elastin and collagen (lysyl oxidase)
ROS (superoxide dismutase)
co-factor roles for copper
ATP7A mutation
Menkes
ATP7B mutation
Wilson’s
Pathogenesis of acrodermatitis enteropathica in Zn deficiency
ZIP4 pathogenic variant (gene mutation)
clinical features of this include:
alopecia
diarrhea
lethargy
Acute eczematous periorificial and acral dermatitis
acrodermatitis enteropathica in Zn deficiency
antibiotics used for which IBD
CD
probiotics used for which IBD
UC
fecal microbiota transplantation used for what IBD
CD and UC
this IBD has goblet cell preservation
CD
this IBD has goblet cell depletion
UC
Uveitis, episcleritis, arthropathy, pyoderma gangrenosum, erythema nodosum, nephrolithiasis, PSC, thromboembolism
extra-manifestations for CD and UC
major side effect for Zn deficiency
diarrhea and dermatitis
Deficiency of ___ affects rapidly proliferating tissues
zinc
Infliximab
3 rapid agents effective for severe active UC
Infliximab
cyclosporine
methylprenisolone IV
effective for maintenance of remission for UC but NOT treatment of active disease
Azathioprine
effective for mild to moderate UC, NOT severe UC
MESALAMINE
what to check for in patient before starting them on 6-MP or AZA
TPMT mutation
folate antagonist that blocks purine synthesis and used for CD only
Methotrexate
continuous colonic inflammation
A.
B
C
C
A