bennett IBD

Methotrexate brands

Trexall, Rheumatrex

Mesalamine brand

Lialda, Apriso, Pentasa,

Asacol, Delzicol

delzicol generic

mesalamine

pentasa generic

mesalamine

asacol generic

mesalamine

Cyclosporine brands

Sandimune, Gengraf, Neoral

neoral generic

cyclosporine

gengraf generic

cyclosporine

Tofacitinib brand

Xeljanz, Xeljanz XR

s/s of IBD

bloody dia

rectal urgeny,

Tenesmus (feeling to pass stools, even when colon is empty),

N,V, weight loss,

fatigue

difference between ulcerative coliits and crohn’s disease

• ulcerative is only in recturm/colon but crohn’s is anywhere

• crohn’s penetrates deeper (“transmural”— thickness of bowel wall), ulcerative is just mucosal

which disease (CD/UC) associated with Th1 at high levels

CD (chron’s)

• fight pathogens INSIDE CELLS— active macropahges

which disease (cd/uc) associated with TH2 in high levels

ulcerative colitis

• fight parasites; allergy associated, produce IgE

what use in mild/moderate UC

aminosalicylate; prednisone; add azathioprine 6-merpto

basic summary UC

Chronic inflammation primarily affecting the inner lining of the colon and rectum, extending continuously from the rectum

• th2 related (allergy)

basic summary of CD

: Chronic inflammation that can affect any part of the GI tract in patchy areas and extend through the entire bowel wall

• th1 associated

how is IBS dif from IBD

• ibs is altered GI sensitivity ; some constip or bloating

• ibd is autoimmnune often. tissue dmanage, more serious d, pain, blood stools, wt loss, fatgiue

what in severe treatment fo UC

IV hdyrocortisone; methylpred

• PO pred and salicyclate for remission

what is first line for UC remission

olsalazine

what is mild-mod drugs for CD

• aminosaliculate

• add metronixadole esp if small intestine type of CD

what use in mod to severe CD

• prednisone PO or IV methylpred

• ADD infiximab if NO repsonse

• ADD azathiorpine if infix no response

what use in remission of CD

aminosalcicylates+ infliximab, or azathio, or methotrex; or 6-mp

supplementary meds for CD and UC

Anti diarrhea, antispasmodics, vitamins B12, vitamin D, calcium, iron, probiotics are also helpful

tbf alpha what do

cytokine produced in repsonse to infalm

• want to DECREASE

whats with eicosanoids

• injury to tissue releases arachdonic acid from the membrane

• active LOX and COX pathways

• eico is one fo the PGs released from COX

what are the Aminosalicylates

mesalamine, sulfasalazine, olsalazine, balsalazide

what do aminosal do (mesalamine, sulfasalazine, olsalazine, balsalazide)

deliver 5-ASA , the substance that is anti-inflam, to intestine — local acting

• better for UC bc right there all long the surface where affected

adrs of olsazlzine (an aminosalic)

watery D, abdom pain

which is cheapst aminsal? what is issue with it?

Sulfasalazine (an azo)

dwhat are two types of anti-inflam drugs (the aminosalc)

• azo — the active 5-ASA is boudn to smth else; colon bacteria have to break it open

• mesalamine — free active 5-ASA; need coatings or enteric relaese or rectal admin to be effective

Sulfasalazine (an azo) importnat INX

sulfa allergy!

Sulfasalazine (azo) adrs

• ha, rash, nvd

  • naus, bone marrow suppression, gi upset, alopecia, myalgia

what drug can cause yellow orange discolor of skin and urine

Sulfasalazine (an azo aminosalcy)

• think bc of its SULFUR

ddi of Sulfasalazine (azo aminosal)— what does it decrease

digoxin, iron, folic acid, PABA drugs (think some antibiotics like Bactrim)

ddi of Sulfasalazine (azo aminosal)— what does it increase

oral anticoags, methotrexate, hypogelmics (what in tarnation does this mean)

what should you not take with Sulfasalazine (an azo aminosal)

antacids, h2ras, ppis

CI for Sulfasalazine (an azo aminosal)

sulfa OR salicylate alleriges; GI obstruction

preg/lactation info for Sulfasalazine (an azo aminosal)

can cause dia in the infant

why use OCS for uc/cd

suppress cyotkines to get active inflam under control

• not long term maintennce

w

which cyotkines OCS suppress

tnf-alpha, IL-1 and il-8

how preds dosed?

qd

which vitamin is folic acid

vit b9

• help in DNA production

when would use iv methylpred

severely ill pts

when/why would use hydrocortisone

enemas, foam, rectal suppositites as formulations

• more absoprtion in colon, less systemic, less systemic adrs

budesonide

adrs for OCS

if use longer than 2 weeks can cause: iatrogenic Cushing's syndrome, adrenal suppression

▪ Insomnia, behavioral changes (primarily hypomania)

▪ Acute peptic ulcers

▪ Protein breakdown (catabolism)

▪ Hyperglycemia

▪ Impaired wound healing

▪ Immunosuppression : lower resistance to infection

▪ Osteoporosis

▪ ↑intraocular pressure

▪ Hypertension and hypokalemia

what diet should be given for OCS taking pts

high protein; K ricj diets

cna you abruptly stop OCS

nooo taper

what are the two thiopurines

azathioprine and 6-mercaptopurine.

thiopurines (azathioprine and 6-mercaptopurine.) what is avtive molecule? which is clsoer to active moelule

• active thioguanines are the active

• 6-MP is closer, aza has to be metabolized to 6-mp THEN the active nucleotide

where glucocort regualted from

HPA, then to ACTH

• from hypothalamus, to pituary that releases adrenocorotipoc hormone

types of conduction. (what the heck) to OCS

1. responsive— taper off

2. dependant— msut have daily low dose

3. non-responsive— no use glucocort

thiopruines (azathioprine and 6-mercaptopurine.) are they long term or for quick remisison

no long term to MAINTAIN remission

MOA for thiopurine (azathioprine and 6-mercaptopurine.)

• 
  

what is with TPMT pathway and all taht

AZA metabolize to 6-mp

• then 6-mp can be metabolized by TPMT into usless metabolites

• 6-mp meta by XO makes 6-thiouric acid, also inactive

• 6-mp by HGPRT makes teh use active meatbolte 6-TGN

the thanksgiving pie lol

WHAT is active metabolite of 6-MP? what is. main ad eff? which enzyme metabolizes it into this?

• metabolite: 6-TGN

• main ad eff00 myleosuppression

• done by the HGPRT

what can cause trouble in pt phemnotype for thiopurines (azathioprine and 6-mercaptopurine)

low TPMT activity— so will have too many acitve 6-TGN as metabolized by HGPRT

what ar ethe purines

As and Gs my dudes

when use thiopurines (azathioprine and 6-mercaptopurine.)

IBD, prevent transplant rejection, RA, multiple scleroris, cancer

how thiopruiesactially work (azathioprine and 6-mercaptopurine.)

The active metabolites interfere with purine metabolism and DNA-related processes, reducing lymphocyte proliferation and activity.

preg wanr in thiopurien

can corss placenta

thiopurines ((azathioprine and 6-mercaptopurine.)) ddi

allopurinol (have ot decrease AZA dose ??)

(azathioprine and 6-mercaptopurine.) adrs

nv, hepatox (from TPMT metabolites)

(azathioprine and 6-mercaptopurine.) thiopurine bbw

lymphoma, leukopenia, thrombocytopenia

(azathioprine and 6-mercaptopurine.) thiopurine monitoring

CBC, liver function tests

methotrextate how dosed in IBD

take PO qWEEK

why methotrexate stay in body a long time

bound to glutamate

methotrexate MOA

folate antagonist

• at low dose— increase adenosine-mediated anti-inflam effects— decrease IL2/inflam

• high dose is cancer, stops cell emdiated immne rxn

is homocysteine good or bad guy

bad guy— we want methionine , if its not being converted it means youre in trouble

what to monitor when on methotrexate

liver function tests

how long avoid methotrex if preg

at least 3 mo before tyring to conceive

adrs methotrexate

myelosuppression, severe oral ulceration/stomatitis, renal, NV, LFT

pneumonitis, photosensitivity, alopecia, crystalluria at high dose

what is antidote for methotrex ?

• analog of tetrahydrofoalte so you can make some DNA

• leucovorin

ddi methotrex

nsaids— prolong mtx levels

• steriods can decrease uptale of methotrex

cyclosporine (sandimmmune, neoral, gengraf) MOA

suppress cell mediated immune rxn by binding to cyclophillin

• inhibits calcineurin; downreg IL-2; immunosuppresion resutls

cyclosporine (sandimmmune, neoral, gengraf) DDI

MOST drugs effect CsA levels bc CYP 3a4 metabolized

cyclosporine (sandimmmune, neoral, gengraf) what are inhibitors that really affect

• azole antifungals (ketoconazole)

• verapamil

• cimetidine

• grapefruit juice

• fluvoxamine

cyclosporine (sandimmmune, neoral, gengraf) what are inducers that affect

• rifampin

• phenytoin

• phenobarb

• carbamazepine

• isoniazid

• st johns wort

cyclosporine (sandimmmune, neoral, gengraf) what immune cells does it ultiamtely get rid of

T and B cells

• by stop forming NFAT by binding to calcineurin to inhibit

• calineur is an enzyme inside T cells that activates them

cyclosporine (sandimmmune, neoral, gengraf) ADRs

• nephrotox

• neurotoxic

• hepatotox

• gingival hyperplasia,

• HTN, increase risk of lymphoma (less immune survelliance means less control over potentially maligant T and B cells), increase risk of infection

cyclosporine (sandimmmune, neoral, gengraf) indications

severe RA , IBD, prevent transplant rejection

cyclosporine (sandimmmune, neoral, gengraf) BW

renal impairment causing increased risk of lymphoma, infection, and HTN

cyclosporine (sandimmmune, neoral, gengraf) monitor what?

BP, renal, electrolytes, CBC, signs of infection

cyclosporine (sandimmmune, neoral, gengraf) how are maintence levels monitored

trough or 2 hour after dosing

how often take methotrex

once a week, 2.5 mg starting dose for IBD/RA— when giving LD its more AICAR which stops ATP synth by stopping adenosine

• in cancer given IV (“high dose” to stop folate synth)

what does IL-2 do

produced by T cells taht recognizes an antigen

• tells t cells to multiply and build up immune resposne

• decreased by MTX, cyclosporine, tacrolimus

what does TNF stand for

tumor necrosis factor

dif between tnf-a and il-2

Il-2 mostly boosts t-cell growth

tnf-a is broad inflammation signal

what are some effects of TnF-a

• inflam signalling

• activating vascualr endothelium

• recruitment of more immune cells

• systemic inflam effects like fever

RELEASE OF MORE CYTOKINES (ILs)

what MOSTLY releases tnf-a? what else can release tnf-a?

MACROPHAGES— wbcs that engulf and digest harmful germs and such — part of innate immunity

• also can be triggered by adaptive immune system (esp Th1)

• non-immune cells— fibroblasts, smooth muscle cells

what is TNF-a like

soluble and membrane bound (sounds polar to me)

what does binding of TNF to receptor on cells do

• activation of NF-kapp B

• increases proinflammatory cytokines

• acitvation and profliefartion of T cells, increase leukocyte migration and apoptosis

what else causes gingigval hyperplasia besides cyclosporine

CCBs

what are the anti-tnf a drugs

infliximab, adalimumab, certolizumab pegol

for infliximab, adalimumab, certolizumab pegol (anti-TNFa), what tesitng do you have to to

PPD testing for TB skin test before use

• anti-TNF drugs can “wake up” latent TB

• RECALL bc TB stays in your macropahges in its latent form

what are generics of monoclonal antinodies called ? what color is book?

• biosimialrs

• “Follow on biologics”

PURPLE

what are generics of small molecules called? what color book?

generics lol

• orange

what is risk of body resistance forming to anti-TNFa ‘s caleld? hint— recall they are mAbs

infliximab, adalimumab, certolizumab pegol

• you form ANTIBODIES to the biologic drug

• “ANTIBODIES TO THE ANTIBODY”; HAMA is human anti-mouse antibodies which is a subset of ATA rxns

infliximab, adalimumab, certolizumab pegol (anti-TNFa) MOA

binds to soluble/membrane bound TNFa— stops t-cells and macrophages so you don’t release as many cytokines

infliximab, adalimumab, certolizumab pegol (anti-TNFa) ADRs

reactivation of latent TB, risk of hep B

• can also cause HF, hematolgoic, hepatotox, leukopenia, pain at site injection