IBD Flashcards
Idiopathic IBD categories
Ulcerative colitis
Crohn’s disease
Ulcerative colitis
Mucosal inflammatory condition affecting the rectum and colon
Crohn’s disease
Transmural inflammation of any part of the GI tract, mouth to anus
Clinical findings for UC
Continuous inflammation (very common) Toxic megacolon Pseudopolyps
UC histology
Nontransmural
Crypt abscesses
Depth of UC ucleration
Superficial
Is UC a risk factor for colorectal cancer?
Yes
Clinical findings for CD
Patchy cobblestone appearance
Perianal involvement
Fistula, perforation, or strictures
Malabsorption/malnutrition - vitamin deficiencies; possible growth retardation
Depth of CD ulceration
May extend to submucosa or deeper
Histology of CD
Transmural lesions
Granuloma
Extraintestinal complications (more common in CD)
Spondylarthritis Peripheral arthritis Ocular Primary sclerosing cholangitis Anemia C diff Hypercoagulability Malabsorption Thromboembolic disease Osteoporosis
Thromboembolic disease in CD
Risk for VTE is three-fold higher than in general population
How is osteoporosis caused by IBD?
D/t systemic inflammation effects on bone, malabsorption of Vit D, and glucocorticoid use; bisphosphonates are the preferred drug of treatment
Smoking in UC
Nicotine offers a protective mechanism
The likelihood of a smoker developing UC is less than half that of a non-smoker
Patients with UC who stop smoking often relapse
Transdermal nicotine patches and UC
Shown improvement in disease remission rates but are not recommended as a standard of care
Smoking and CD
Ppl who smoke are 2x as likely to have CD
Patients who stop smoking will see reduction in severity of their condition
Assumed etiologies for IBD
Infectious Genetic Environmental Psychologic Immunologic
Genetics and IBD
CD is common among relatives
1st degree relatives are 13x more likely to suffer from IBD
Genes have been identified for UC and CD
Environment and IBD
No clear connection to diet
NSAID use - PG inhibition appears to impair the protective mechanism of the mucosal barrier in the GI tract
Psychology and IBD
Clear association between mental health and remissions/flares
Immunology and IBD
Cytokines - inappropriate T cell response to intestinal flora
TNF-alpha - activates coagulation and promotes granuloma formation (production enhanced in patients with CD)
Mild IBD
+/- blood in stool
No systemic sx
Normal ESR
Moderate IBD
+/- blood in stool
Minimal systemic sx
Normal ESR
Severe
+ blood in stool
+ systemic sx
Increased ESR (> 30)
CDAI
Chrone’s disease Activity Index
Mostly done in trials
Measures CD
IBDQ score
QOL
Genetics tests for IBD
Prometheus Labs
May indicate how severe a patient’s dz will be
Diagnosis of IBD
Pt sx
PE
Labs
Radiographic/endoscopic findings
Labs for IBD diagonsis
Compares carious IgG and IgM in patient with a database of IBD patients
Not extremely accurate
Non-pharm treatment of IBD
Nutrition (avoid exacerbating foods, use parenteral nutrition if needed)
Surgery (indications include uncontrolled disease despite max therapy, presence of complications or presence of premalignant changes)
Pharm treatment of IBD
Aminosalicylates Corticosteroids immunosuppressants Cipro/flagyl TNF-alpha Humanized monoclonal antibody to alpha-4 integrin Tofacitinib
Aminosalicylates
Balsalazide
Osalazine
Sulfasalazine
Mesalamine
Aminosalicylates MOA
Modulates leukotrienes to inhibit inflammatory response
Aminosalicylates time to effectiveness
2-4 weeks, treat for 6-8 weeks at full treatment dose
Aminosalicylates MD
50% treatment dose
Aminosalicylates and monitoring
SCr prior to starting therapy and periodically thereafter d/t risk for nephrotoxicity
Balsalazide site of action
Colon
Osalazine site of action
Colon
Osalazine ADR
Dose-related diarrhea
Sulfasalazine ADR
N/V
Ab pain
CI: sulfa allergy
Mesalamine general
Easier to tolerate than sulfasalazine
Mesalamine brands and site of action
Rowasa: rectum; terminal colon Delzicol/Asacol HD: distal ileum; colon Canasa: rectum Pentasa: small bowel; colon Lialda: colon Apriso: colon
Mesalamine monitoring
folic acid level
Mesalamine DDI
Antacids H2RAs PPIs **May cause premature relase of delayed release products Preg risk cat D
Corticosteroids MOA
Inhibit inflammatory mediator release (cytokines)
Corticosteroids
Prednisone
Methylprednisolone IV
Budesonide
Budesonide bioavailability
Poorly absorbed w/limited bioavailability d/t an extensive 1st pass metabolism by the liver allowing it to produce therapeutic benefit with reduced systemic toxicity
Budesonide
Enterocort EC - for CD in the terminal ileum or right colon (12 week treatment then taper)
Uceris - UC (8 week treatment then taper)
Budesonide monitoring
BMD yearly, receive vit D and calcium if long term use required
Immunosuppresants
Azathioprine, 6-MP
CsA
MTX
Azathioprine, 6-MP MOA
Antagonizes purine metabolism causing immunosuppresion
how long until a patient on AZA, 6-MP sees a benefit
3 months (use something quicker in the meantime)
AZA, 6-MP monitoring
Hg WBC Plts LFTs Amylase TPMT testing may help prevent toxicity
CSA MOA
Inhibits production and release of IL-2 causing immunosuppression
CsA IV use
Severe UC and CD unresponsive to IV steroids
MTX use
CD only
MTX MOA
Anti-inflammatory and immunosuppression through irreversible dihydrofolate reductase inhibition
MTX monitoring
CBC
LFTs
SCr
MTX DDIs
PPIs - appears to only impact high dose MTX used in chemo regimens
Cipro/flagyl use
CD only
- Fistulizing Crohn’s: abx x 3 months
- Potential role in post-op CD pt (pouchitis)
Cipro/flagyl MOA
Benefit is thought to be through inhibiting bacterial stimulation of the inflammatory process
TNF-alpha antagonists MOA
Monoclonal ab that bind to human TNF-alpha thereby interfering with endogenous TNG alpha activity
TNF-alpha antagonists BBW
- Serious infx (including tuberculosis, invasive fungal and other opportunistic infxns), some with fatalities, have been reprted in patients receiving TNF-blocking agents
- Pts should be evaluated for TB risk factors and latent TB infxn (w/ a tuberculin skin test) prior to therapy. Tx of latent TB should be initiated before use. Pts with initial neg TB skin tests should receive continued monitoring for TB throughout treatment
TNF-alpha antagonists
Infliximab
Adalimumab
Certolizumab
Infliximab uses
Adults/pediatrics: CD or UC
Adults: fistulizing CD
Infliximab ADR
Infusion rxn treated with benadryl and APAP (pre-med for future doses)
Adalimumab uses
Adults/peds: CD/UC
Certolizumab uses
CD in adults only
TNF-alpha antagonists monitoring
CRP Fecal calprotectin Lactoferrin Albumin Antidrug ab Anti-TNF drug level (if pt loses response to drug)
TNF-alpha antagonists: if pt loses response with subtherapeutic drug levels AND low or no abs?
Increase anti-TNF and/or decrease interval
Consider adding thiopurine/MTX if not already on
TNF-alpha antagonists: if patient loses response with subtherapeutic drug levels and high ab levels
Switch to different TNF-alpha antagonists
TNF-alpha antagonists: if patient loses response with therapeutic drug levels
switch to vedolizumab w/ or w/o immunosuppressant (if CD; if UC, DC drug)
Humanized monoclonal ab to alpha-4 integrin MOA
Inhibit leukocyte adhesion and migration (vedolizumab in GI tract only)
Humanized monoclonal ab to alpha-4 integrin uses
Inducing and maintaining clinical response and remission in adult patients with mod-severe active CD (natalizumab and vedulizumab) or UC (vedolizumab) with an inadequate response to, or are unable to tolerate conventional CD/UC therapies and TNF-alpha antagonists
What must be up-to-date before starting Humanized monoclonal ab to alpha-4 integrins
Immunizations
Humanized monoclonal ab to alpha-4 integrins
Natalizumab
Vedolizumab
Natalizumab ADR
Progressive multifocal leukoencepholopathy in MS
Severe cholestatic injury
Natalizumab monitoring
LFTs (esp during first week of therapy)
Vedolizumab ADR
HA
Arthralgia
Nasopharyngitis
Tofacitinib (Xeljanz)
Janus Associated Kinase inhibitor approved for RA
Currently being studied in UC patients with mod-severe disease non-responsive to other treatment
Vaccines for IBD
Flu PCV13 or PPSV23 Zoster Varicella Yellow fever Hep B Meningococcal
Flu vaccine and IBD
Annually
If on immunosuppressant: non-live trivalent
PCV13 or PPSV23 vaccine and IBD
If on immunosuppressant
Should have PPSY23 booster 5 years after 1st dose
Zoster vaccine and IBD
Not on immunosuppressants or on low dose MTX, AZA, or 6-MP
Not recommended if on anti-TNF therapy
Varicella vaccine and IBD
Assess for prior exposure and vaccinate if naive PRIOR to initiating immunosuppressant therapy
Yellow fever vaccine and IBD
Vaccinated prior to travel
Assessed before travel
-If highly immunosuppressed - should not travel
-To stop immunosuppressants in order to get vaccine - wait 3 months before vaccination; then wait at least 4 weeks to restart immunosuppressant
Hep B vaccine and IBD
HBV can be re-activated in an immunocompromised patient
Test for HBV infection prior to starting treatment
Check for immunity to HBV and vaccinate if not immune prior to starting treatment
1-3 months after vaccination, check a titer to be sure patient is immune
Check a titer every 1-2 yr thereafter; give a single booster shot if necessary
Health screenings in IBD
Cervical cancer - annual
Depression/anxiety screening
Melanoma
Non-melanoma squamous cell cancer screening - > 50 yo on immunosuppressants
Osteoporosis - those with conventional risk factors should be screened at the time of diagnosis and periodically after diagnosis
