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IBD Flashcards

1
Q

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

A

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

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2
Q

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

A
  • immune
  • microflora
  • intestinal
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3
Q

Etiology

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

A
  • UC
  • CD
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4
Q

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

A

COX-2

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5
Q

UC Clinical Presentation

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

A

fecal calprotectin (FC)

also used in CD

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6
Q

IBD Treatment Overview

Non-PCOL

A

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

surgery
- resecting areas of inflammation

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7
Q

IBD Treatment Overview

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

A
  • sulfasalazine, mesalamine
  • azathioprine, mercaptopurine, cyclosporine, methotrexate
  • metronidazole, ciprofloxacin
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8
Q

ASA Agents

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

A

inactive
mesalamine

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9
Q

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

A
  • rapidly
  • left-sided disease
  • proctitis
  • topical, oral
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10
Q

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

A
  • Apriso
  • Lialda
  • Pentasa
  • Asacol HD, Delzicol, balsalazide (Colazal)
  • Olsalazine (Dipentum)
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11
Q

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

A
  • sulfapyridine
  • sulfonamide
  • bleeding
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12
Q

T or F: sulfasalazine is much better tolerated than mesalamine

A

FALSE

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13
Q

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

A

anti-inflammatory
remission
systemic

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14
Q

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 ___

A
  • systemic
  • 8, 16
  • Enterocort, Uceris
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15
Q

Corticosteroids: Budesonide

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

A
  • ketoconazole
  • systemic
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16
Q

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 ___

A
  • prednisone, prednisolone
  • methylprednisolone, hydrocortisone
  • remission
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17
Q

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

A
  • calcium, D
  • bisphosphonates
  • bone
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18
Q

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

A
  • 5-ASA, steroids
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19
Q

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

A

prodrug

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20
Q

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

A
  • marrow
  • TPMT
21
Q

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)

A
  • CD
  • long
  • steroids
  • double
22
Q

Cyclosporine

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

Monitoring
BP
BUN/SCr
LFTs
cya tr. conc

A

nephrotoxicity

23
Q

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

A
  • CYP3A, P-gp
  • antifungals, CCBs
  • phenytoin, rifampin
24
Q

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)

A
  • CD
  • steroid
  • folic
  • teratogenic
25
Q

Methotrexate

CI
- ___
- pleural effusions
- chronic liver disease/EtOH abuse
- immunodeficiency
- preexisting blood dyscrasias
- leukopenia/t.cytopenia
- ClCr < ___ ml/min

monitoring
- CXR
- CBC
- SCr
- LFTs

A
  • pregnancy
  • 40
26
Q

Biologics: TNF-a antagonsits

CD and UC
- ___ (Remicade)
- ___ (Humira)

UC
- ___ (Simponi)

CD
- ___ (Cimzia)

A
  • infliximab, adalimumab
  • golimumab
  • certolizumab pegol
27
Q

Biologics: anti-integrin

CD
- ___ (Tysabri)

UC and CD
- ___ (Entyvio)

A
  • natalizumab
  • vedolizumab
28
Q

Biologics: IL

CD and UC
- ___ (Stelara)
- ___ (Skyrizi)

UC
- ___ (Omvoh)

A
  • ustekinumab, risankizumab-rzaa
  • mirikizumab-mrkz
29
Q

New Small molecule drugs: JAKs

UC
- ___ (Xeljanz)

UC and CD
- ___ (Rinvoq)

A
  • tofacitinib
  • upadacitinib
30
Q

New Small molecule drugs: S1Ps

UC
- ___ (Zeposia)
- ___ (Velsipity)

A
  • ozanimod
  • estrasimod
31
Q

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)

A
  • PPD, CXR, 3
  • lymphoma
  • demyelinating
  • CHF
32
Q

TNF-α inhibitors: Monitoring

  • ___ , ___
  • s/s of infection
  • UA
  • CBC
  • SCr, electrolytes
  • ___
  • Hep B/C
A
  • CXR, PPD
  • LFTs
33
Q

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

A

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

34
Q

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)

A
  • vitals
  • infusion
  • TDM
35
Q

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)

A
  • UC, CD
  • SQ
  • ADAs
  • TDM
36
Q

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

A

UC
SQ
ADAs
TDM

37
Q

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

A

CD
ADAs
TDM

38
Q

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

A
  • α, integrins
  • CD
  • TNF-α
  • TNF-α, immunosuppressants
  • infusion
  • 12
39
Q

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

A
  • PML
  • JC
  • 2
  • immunosuppressant
  • JC
40
Q

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*

A
  • α4β7, integrin
  • natalizumab
  • TDM
41
Q

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

A

IL-12, IL-23
- CD, UC

42
Q

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 ( ___ ))

A
  • TDM
  • carcinoma
  • immunosuppressant
  • neurotoxicity, RPLS, PRES
43
Q

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

A
  • IL-23
  • CD
  • UC
44
Q

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 ___

A
  • HA, nasopharyngitis
  • LFTs
  • lipids
45
Q

Risankizumab-rzaa (Skyrizi)

monitoring
- ___ , ___
- Hep B, C
- ___
- ___
- renal function
- infection

A
  • CXR, PPD
  • lipids
  • LFTs
46
Q

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

A
  • IL-23p19
  • UC
47
Q

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

A
  • HA
  • LFTs
48
Q

Mirikizumab-mrkz (Omvoh)

  • ___ , ___
  • Hep B, C
  • ___
  • ___
  • renal function
  • infection
A
  • CXR, PPD
  • lipids, LFTs

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