IBD Flashcards by Reagan Smith

IBD - mucosal inflammatory conditions with chronic or reecurring immune respone and inflammation of GI tract

2 types
1) ___ - mucosal inflammation confined to rectum and colon
2) ___ - transural inflammation of GI tract that can affect any part from the mouth to anus

1) ulcerative colitis (UC)
2) crohn’s disease (CD)

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Etiology

combination of immunologic, infectious, genetic, enviromental factors
- ___ dysregulation
- ___ of GI tract may trigger
Immunologic
- both autoimmune and non-autoimmune mechanisms
- innate immune system involves ___ barrier function, is associated with secretions in response to stimuli

immune
microflora
intestinal

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Etiology

Smoking:
- potentially protective in ___
- increases frequency/severity of ___

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Etiology - drug related causes

NSAIDs
- may trigger disease occurance or lead to flares
- unclear if ___ selective agents are associated with a decreased risk
- generally avoid

antibiotics
- potential assocaiation; idk why

COX-2

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UC Clinical Presentation

___ corelates with degree of inflammation
- more sensitive and specific than serum markers

fecal calprotectin (FC)

also used in CD

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IBD Treatment Overview

Non-PCOL

nutrition
- no specific diet shown to be beneficial
- address nutritional deficiencies/impaired absorption

surgery
- resecting areas of inflammation

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IBD Treatment Overview

PCOL
no agents are curative
- ASAs (aminosalicylates) (2)
- corticosteroids (local and systemic)
- immunomodulators (4)
- biologics (a lot)
- antimicrobials (2)

sulfasalazine, mesalamine
azathioprine, mercaptopurine, cyclosporine, methotrexate
metronidazole, ciprofloxacin

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ASA Agents

sulfasalazine = sulfapyridine + 5-ASA ( ___ )
- sulfapyridine is ___, associated with ADRs
- 5-ASA exertis actions locally
- anti-inflammatory effects, free radical scavenging

inactive
mesalamine

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ASA Agents: Mesalamine

can administer mesalamine alone
- ___ and completely absorbed in small intestine but not colon

formulation is important to deliver to affected area
* topical (enemas): ___
* suppository: ___
* oral -> delayed/controlled release

generally ___ is more effective than ___
- can use oral and topical together

rapidly
left-sided disease
proctitis
topical, oral

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Oral Mesalamine Agents
- once daily (2)
- QID (1)
- TID (3)
- BID (1)

Apriso
Lialda
Pentasa
Asacol HD, Delzicol, balsalazide (Colazal)
Olsalazine (Dipentum)

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ASA Agents: ADRs

sulafsalazine -> ___ is associated with ADRs
- N/V
- anemia
- pneumoitis, lymphoma, nephritis

may be associated with hypersensitivty rxn in ___ allergy

monitor:
- CBC and LFTs at baseline
- BUN/SCr

drug interactions:
- antiplatelet/anticoags/NSAIDs may increase ___ risk

sulfapyridine
sulfonamide
bleeding

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T or F: sulfasalazine is much better tolerated than mesalamine

FALSE

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Corticosteroids

MOA: ___ (note, unclear whether primary effect systemic or local)
- can be used parenterally (severe
exacerbation/complication), orally, or rectally
- use for induction of ___ , but NOT for maintenance

Rectal Hydrocortisone (generally ~100-200 mg per day):
- suppositories (Proctocort, Hemril), foam (Cortifoam), enema (Cortenema, Colocort)
- note that ___ absorption is possible with rectal formulations

anti-inflammatory
remission
systemic

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Corticosteroids: Budesonide

administered PO in CR formulation
- extensive first pass metabolism -> minimal ___ exposure (9-21%)
- 6-8 mg/day for up to __ weeks (possibly ___ wks)
- 2 brand names: ___ and ___

systemic
8, 16
Enterocort, Uceris

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Corticosteroids: Budesonide

Budesonide
drug interactions:
- CYP3A inhibitors ( ___ , grapefruit juice, many others)
- may increase ___ exposure

ketoconazole
systemic

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Systemic Corticosteroids

oral ___ or ___
- 40-60 mg/day
- taper 5-10 mg/week until a dose of 20 mg/day is reached, then taper 2.5 mg/week
- intravenous ___ (16-20 mg q 6 h) or ___ (100 mg q 8 h)
- may be used for disease flares/induction of ___

prednisone, prednisolone
methylprednisolone, hydrocortisone
remission

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Systemic Corticosteroids

ADRs:
- give ___ and vitamin __ while on steroids
- may consider ___ in patients with risks for osteoporosis, use over 3 months, recurrent users

consider occasional ___ mineral density scan (DEXA) in pts > 60, pts w risks for osteoporosis, pts using for > 3
months, recurrent users

calcium, D
bisphosphonates
bone

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Azathioprine (AZA) and Mercaptopurine (6-MP)

can be effective in long term txt of UC and CD
- generally reserved for pts who fail ___ tx, and/or pts who are refractory to/dependent on ___
- can maintain remission, steroid sparing (limited role in induction)
- can use in combo with other drugs
- generally need to be used for extended periods (weeks-months) before benefits observed

5-ASA, steroids

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Azathioprine (AZA) and Mercaptopurine (6-MP)

AZA is a ___ that is rapidly converted to 6-MP
* AZA: 0.5-1.5 mg/kg IBW, increase to a max of 2.5 mg/kg/d
* MP: 0.25-0.5 mg/kg IBW, increase to a max of 1.0-1.5 mg/kg/d

prodrug

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AZA and 6-MP

ADRs
*GI: N/V/D, anorexia, stomatitis
*hematologic: bone ___ suppression
*hepatic: hepatotoxicity
*idiosyncratic: fever, rash, arthralgia, pancreatitis

Monitoring:
- ___ (PGx)
- CBC
- LFTs

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marrow
TPMT

Cyclosporine

can be effective inducing remission in patients with refractory IBD (not recommended for ___ )
- not an option for ___ term use (i.e., use as “bridge therapy”)
- generally reserved for pts who are refractory to/dependent on ___
- initial continuous IV infusion 2-4 mg/kg/day
- PO conversion: ___ the IV dose, administered in divided doses q12h
- taper over several weeks if response (up to several months)

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CD
long
steroids
double

Cyclosporine

ADRs
- ___ (dose related)
- neurotoxicity
- metabolic (HTN, hyperlipidemia, hyperglycemia)
- GI upset, gingival hyperplasia, hirsutism

Monitoring
BP
BUN/SCr
LFTs
cya tr. conc

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nephrotoxicity

Cyclosporine

DI
substrate for ___ and ___

drugs that increase cyclosporine [ ]
- azole ___ , macrolide antibiotics, ___ , grapefruit

drugs that decrease cyclosporine [ ]
- ___ , ___

Tacrolimus
- has been used in refractory disease although role less defined

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CYP3A, P-gp
antifungals, CCBs
phenytoin, rifampin

Methotrexate (MTX)

can be used in ___
- may have ___ sparing effects, assist in inducing remission, allow steroid-tapering
- role in UC less defined (may have role in combo therapy)

ADRs
* hematologic: bone marrow suppression (add ___ acid 1
mg/day)
* GI: N/V/D, stomatitis, mucositis
* hepatic: cirrhosis, hepatitis, fibrosis
* pulm: hypersensitivity pneumonitis
* derm: rash, urticaria, alopecia
* ___ (contraception)

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CD
steroid
folic
teratogenic

# Methotrexate CI - ___ - pleural effusions - chronic liver disease/EtOH abuse - immunodeficiency - preexisting blood dyscrasias - leukopenia/t.cytopenia - ClCr < ___ ml/min monitoring - CXR - CBC - SCr - LFTs

- pregnancy - 40

# Biologics: TNF-a antagonsits CD and UC - ___ (Remicade) - ___ (Humira) UC - ___ (Simponi) CD - ___ (Cimzia)

- infliximab, adalimumab - golimumab - certolizumab pegol

# Biologics: anti-integrin CD - ___ (Tysabri) UC and CD - ___ (Entyvio)

- natalizumab - vedolizumab

# Biologics: IL CD and UC - ___ (Stelara) - ___ (Skyrizi) UC - ___ (Omvoh)

- ustekinumab, risankizumab-rzaa - mirikizumab-mrkz

# New Small molecule drugs: JAKs UC - ___ (Xeljanz) UC and CD - ___ (Rinvoq)

- tofacitinib - upadacitinib

# New Small molecule drugs: S1Ps UC - ___ (Zeposia) - ___ (Velsipity)

- ozanimod - estrasimod

# TNF-a inhibitors: ADRs increase risk of serious infections - avoid if active infection - tuberculin test ( ___ ), ___ , Hepatitis B/C prior to therapy - ensure vaccinations up to date - live vaccines contraindicated during tx and for __ mo after injection site reactions injection site reactions (SC injections) and infusion related reactions (IV) risk of malignancy ( ___ ) - HSTCL risk of ___ disease - C/O in pts w history of cancer, demyelinating CNS disease, optic neuritis may exacerbate ___ (c/o in NYHA class III/IV)

- PPD, CXR, 3 - lymphoma - demyelinating - CHF

# TNF-α inhibitors: Monitoring - ___ , ___ - s/s of infection - UA - CBC - SCr, electrolytes - ___ - Hep B/C

- CXR, PPD - LFTs

# TNF-a inhibitors: Infliximab (Remicade) ___ and __ - mod - severe active CD and UC, steroid-dependent or fistulizing disease - ___ and ___ therapy IV ___ (2 hours): 5 mg/kg at 0, 2 and 6 weeks, then 5-10 mg/kg q 8 weeks development of ___ (ADAs) - decrease treatment response, potentially increase chance of infection - up to 10% of pts/year need to d/c infliximab - can escalate dose, decrease dosing interval - ___ (drug and antibodies) may be of value combining with ___ may increase risk of ADRs hepatosplenic T-cell lymphoma (HSTCL) risk - if co-administered w ___ infusion-related reactions - acute or delayed

UC, CD - induction, maintenance - infusion - antibodies - TDM - immunosuppressives - AZA

# Infliximab (Remicade) Monitoring (in addition to class monitoring) - s/s of infection - ___ (each dose) - ___ reactions (each dose) - ___ (consider if treatment failure) poorly defined targets (target trough ≥ 5-10 μg/ml)

- vitals - infusion - TDM

# Adalimumab (Humira) ___ and ___ - mod - severe active CD and UC, steroid-dependent - can use for pts with poor response to infliximab - induction and maintenance therapy ___ injection: 160 mg at wk. 0, 80 mg at wk. 2, then 40 mg every second wk. - self-administration technique important - in non-response/loss of response can increase dose to 80 mg q other wk. or 40 mg q wk. development of ___ - human derived (potentially less likely than infliximab) - measurement of antibodies possible ___ possible - poorly defined targets (target trough ≥ 8-12 μg/ml)

- UC, CD - SQ - ADAs - TDM

# Golimumab (Simponi) indication: ___ - mod - severe active UC, steroid-dependent - induction and maintenance therapy ___ injection: 200 mg at wk. 0, 100 mg at wk. 2, then 100 mg every 4 wks - self-administration technique important - no guidelines for dose escalation development of ___ - human derived (potentially less likely than infliximab) ___ possible

UC SQ ADAs TDM

# Certolizumab pegol (Cimzia) indication: ___ - mod - severe active CD, steroid-dependent - induction and maintenance therapy SQ injection: 400 mg at wk. 0, 2, and 4, then 400 mg every 4 wks - self-administration technique important - no guidelines for dose escalation development of ___ - ___ possible (poorly defined targets) - target trough ≥ 20 μg/ml

CD ADAs TDM

# Natalizumab (Tysabri) MOA: anti- __ -subunit of ___ (prevents leukocyte adhesion/migration) indication: ___ - inducing and maintaining remission - can use in pts who fail/don’t tolerate ___ inhibitors - NOT to be used in combination w ___ or ___ 300 mg IV q 4 wks - 1 hour ___ - d/c in patients w no benefit by ___ weeks and/or who are still steroid dependent within 6 months

- α, integrins - CD - TNF-α - TNF-α, immunosuppressants - infusion - 12

# Natalizumab (Tysabri) associated with ___ - rare, lethal/disabling, untreatable CNS disorder related to opportunistic viral infection ( __ virus) increased risk with: - longer duration of therapy (> __ years) - prior ___ use - __ antibody positive other ADRs similar to other biologics - can see hypersensitivity reactions, ADAs

- PML - JC - 2 - immunosuppressant - JC

# Vedolizumab (Entyvio) anti-___ ___ antibody (expressed on subset of T-lymphocytes) indicated: ___ and ___ - inducing and maintaining remission, decreasing steroid dependence 300 mg IV at 0, 2, and 6 wks, then q 8 wks thereafter (infused over 30 min) ADRs similar to other biologics - can see hypersensitivity reactions, ADAs - PML not observed however close monitoring warranted due to similar MOA of ___ ___ possible * vedolizumab induction (wk 6) 33.7 38.3 μg/ml* * vedolizumab maintenance (q 8 week dosing) 33.7-38.3 μg/ml*

- α4β7, integrin - natalizumab - TDM

# Ustekinumab (Stelara) ___ and ___ antagonist - ___ and ___ - induction: ≤ 55 kg 260 mg IV x 1 55 kg – 85 kg: 390 mg IV x 1 > 85 kg: 520 mg IV x 1 - maintenance: 90 mg SQ q 8 weeks

IL-12, IL-23 - CD, UC

# Ustekinumab (Stelara) ADRs similar to other biologics - hypersensitivity possible (including anaphylaxis and angioedema) - ADAs - ___ possible - ustekinumab 1.0-4.5 μg/ml* - reports of rapidly developing cutaneous cell ___ in patients with risk factors * monitor all patients * monitor closely in patients > 60, with prolonged ___ therapy, and with history of phototherapy possible ___ (reversible posterior leukoencephalopathy syndrome ( ___ ) , posterior reversible encephalopathy syndrome ( ___ ))

- TDM - carcinoma - immunosuppressant - neurotoxicity, RPLS, PRES

# Risankizumab-rzaa (Skyrizi) selective ___ antagonist ___ (moderate-severe disease) induction: * 600 mg IV weeks 0, 4, and 8 maintenance * 180 or 360 mg SQ at week 12 and q 8 weeks thereafter * use lowest effective dose to maintain response ___ (moderate-severe disease) induction: * 1,200 mg IV weeks 0, 4, and 8 maintenance * 180 or 360 mg SQ at week 12 and q 8 weeks thereafter * use lowest effective dose to maintain response

- IL-23 - CD - UC

# Risankizumab-rzaa (Skyrizi) common: - ___ , ___ , arthralgia, abdominal pain, anemia, nausea ADRs similar to other biologics - infections/latent infections (TB) - vaccinations necessary, avoid live vaccines - hypersensitivity possible - ADAs potential hepatotoxicity (increase in ___ ) - monitor LFTs and bilirubin at baseline and by week 12 increases in ___

- HA, nasopharyngitis - LFTs - lipids

# Risankizumab-rzaa (Skyrizi) monitoring - ___ , ___ - Hep B, C - ___ - ___ - renal function - infection

- CXR, PPD - lipids - LFTs

# Mirikizumab-mrkz (Omvoh) IL- ___ antagonist * ___ (moderate-severe disease) induction: - 300 mg IV weeks 0, 4, and 8 maintenance - 200 mg SQ at week 12 and q 4 weeks thereafter

- IL-23p19 - UC

# Mirikizumab-mrkz (Omvoh) common: - ___ , arthralgia, rash, injection site reaction ADRs similar to other biologics - infections/latent infections (TB) - vaccinations necessary, avoid live vaccines - upper respiratory tract infections - hypersensitivity possible - ADAs potential hepatotoxicity (increase in __) - monitor at baseline and for first 24 weeks

- HA - LFTs

# Mirikizumab-mrkz (Omvoh) - ___ , ___ - Hep B, C - ___ - ___ - renal function - infection

- CXR, PPD - lipids, LFTs

IBD Flashcards

(48 cards)