IBD Flashcards
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)
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
Etiology
Smoking:
- potentially protective in ___
- increases frequency/severity of ___
- UC
- CD
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
UC Clinical Presentation
___ corelates with degree of inflammation
- more sensitive and specific than serum markers
fecal calprotectin (FC)
also used in CD
IBD Treatment Overview
Non-PCOL
nutrition
- no specific diet shown to be beneficial
- address nutritional deficiencies/impaired absorption
surgery
- resecting areas of inflammation
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
ASA Agents
sulfasalazine = sulfapyridine + 5-ASA ( ___ )
- sulfapyridine is ___, associated with ADRs
- 5-ASA exertis actions locally
- anti-inflammatory effects, free radical scavenging
inactive
mesalamine
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
Oral Mesalamine Agents
- once daily (2)
- QID (1)
- TID (3)
- BID (1)
- Apriso
- Lialda
- Pentasa
- Asacol HD, Delzicol, balsalazide (Colazal)
- Olsalazine (Dipentum)
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
T or F: sulfasalazine is much better tolerated than mesalamine
FALSE
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
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
Corticosteroids: Budesonide
Budesonide
drug interactions:
- CYP3A inhibitors ( ___ , grapefruit juice, many others)
- may increase ___ exposure
- ketoconazole
- systemic
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
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
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
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
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
- 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)
- 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
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
- 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)
- 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
