29/30 - IBD Flashcards
IBD Risk Factors
Protective Effects
HIGH FIBER DIET
- *HYGIENE**
- *Larger Family** / # of siblings / living on FARM / PET exposure
Smoking / Apendectomy
only for UC
Which IBD based on Risk Factor?
SMOKING = PROTECTIVE
APENDECTOMY = Protective
UC
UC = Smoking / Apendectomy is GOOD
IBD
Risk Factors
NSAIDS / ORAL CONTRACEPTIVES
Sedentary Lifestyle
Stress –> gut inflammation
VITAMIN D Deficiency
Allergy to cow milk / high refined sugar intake
Poor Sleep Quality –> inflmamation
Dysbiosis luminal MICROBIOTA
10-25% have Family History
IBD Diagnosis
PHYSICAL EXAM
ENDOSCOPY** + **BIOPSY
GOLD STANDARD for Diagnosing IBD
Colonoscopy (5ft) / Sigmoidoscopy (2ft)
EGD = CD only
Esophagogastroduodenoscopy, doesnt include Jejunum/ileum
Wireless Video Capsule
visualize small bowel,gets STUCK, not used often
Imaging Studies = CT Scan / MRE
evaluates the upper GI tract
Ulcerative Colitis Differences
Disease Location
Endoscopic Visualization
Pathalogy
Disease Location
confined to JUST THE COLON (okay for EGD)
Endoscopic Visualization
- *Diffuse Superficial Inflammation / loss of Vascular Structure**
- *PSEUDOPOLYPS**
- *Erythema / Friability / Superficial Ulceration**
Pathalogy
Cypt ATROPHY / Neutrophil Infiltration
DIstortion of villous architecture / Paneth Cell metaplasia
Crohn’s Disease Differences
Disease Location
Endoscopic Visualization
Pathalogy
Disease Location
ENTIRE GI TRACT, oral cavity -> Rectom
commonl affeccts Terminal Ileum
Endoscopic Visualization
- *Granulomatous Inflammation = COBBLESTONE**
- *Skip Lesions** / transmural inflammation
Pathalogy
Crypt abscesses / granulomas
inflammation w/ lymphoid aggregates
Antibody Tests
IBD Serologic Markers
Used to:
DISTINGUISH UC from CD
C-Reactive Protein
IBD Serologic Markers
Non-specific
Can correlate with DISEASE ACTIVITY
&
be used DURING FLARE
Fecal CalProtectin
IBD Serologic Markers
Stool Marker
indentifies LARGE intestinal Inflammation
Correlates with Disease Activity
&
can assist with monitoring Disease PROGRESSION
Naming of UC
Proctitis = Rectum
only rectum –> 60-95% of pts
Proctosigmoiditis** = Rectum + Sigmoid Colon
Pancolitis
inflammationt hat extends Past splenic flexure = ALL COLON
Left Sided or Distal Disease
inflammation that extends to splenic Flexure
Which IBD, Clinical Manifestation
AB Pain / Mass
Fatigue / Weight Loss
Fever
Chronic / Nocturnal Diarrhea
CROHNS DISEASE
More common in Females, entire GI tract
Which IBD, Clinical Manifestation
Diarrhea +/- Blood
Tenesmus
urge to go when you cant
^Stool Urgency / Frequency
Rectal Bleeding
Toxic Megacolon
ULCERATIVE COLITIS
ExtraIntestinal Manifestation = EIM
20-40% IBD patients will have inflammation in:
Other Organ Systems
- *Treating IBD –> treats EIM**
- may or may NOT correlate with IBD flare*
Rheuma / Derma / Hepata
Ocular / Hemat / Bones
Nephro / Pancrea
Truelove & Witts
Determines Criteria for WHAT & Based on What?
- *UC**
- *Truelove + Witts**
Mild - Moderate - Severe - Fulminant
Based on:
Stool Frequency / Blood in Stools
Temp / HR / HgB / ESR
CDAI
Determines criteria for WHAT?
&
Severe/Fulminant Criteria
- *CD**
- *Crohn’s Disease Activity Index**
Severe / Fulminant
CDAI > 450
Persistant Symptoms despite treatment w/ steroids/biologics
OR
High Temp / Vomiting / Obstruction
Peritoneal Signs / Cachexia / Abscess
AminoSalicylates
SulfaSalazine / Balsalazide / Olsalazine
5-ASA = Mesalamine
Indicated for what IBD / Severity?
Action / MoA
First Line Therapy for:
MILD-MODERATE IBD
to both Induce & Maintain Remission
UC > CD
in terms of effectiveness
Exerts pharmacologic action TOPICALLY in the gut
- *Anti-Inflammatory**
- inhibits* proinflammatory prostaglandins / leukotrines / cytokine synthesis
- *Immunosupressive**
- BLOCKS* lymphocyte DNA synthesis / T-cell Proliferation
Sulfasalazine
AminoSalicylate
Site of Action / Clinical Pearl
Azulfidine @COLON
Male INFERTILITY (reversible)
may turn Urine ORANGE / stain contacts
Needs Folic Acid supplementation
- *Sulfasalazine = PRODRUG**
- *Mesalamine (5-ASA) is the ACTIVE drug**
- *Sulfapyridine causes the SIDE EFFECTS** = HEADACHE
Sulfasalazine
AminoSalicylate
Formulation / Hypersensitivity
- *Sulfasalazine = Prodrug**
1) Mesalamine = 5-ASA = Active Drug
2) SULFAPYRIDINE = causes Side effects - *DOSE RELATED**, can cause HEADACHE / nausea + fatigue
Hypersensitivity / SULFA ALLERGY
NOT DOSE RELATED
Should be stopped immediately if:
SJS / Fever / Arthralgias / Hepatic or Hematologic Toxicity
Olsalazine
AminoSalicylate
Site of Action / Clinical Pearl
- *Dipentum @ COLON**
- *2X 5-ASA** joined by AZO bond
Same clinical pearls as Balsalazide
SA: HA / Nausea / Ab pain
WATERY DIARRHEA
15% –> should be switched to –> MESALAMINE agent
Balsalazide
AminoSalicylate
Site of Action / Clinical Pearl
- *Colazal @ COLON**
- *5-ASA** linked to inert unabsorbed carrier molecule
Same clinical pearls as Olsalazine
SA: HA / Nausea / Ab pain
WATERY DIARRHEA
15% –> should be switched to –> MESALAMINE agent
- *Mesalamine**
- *5-ASA (Aminosalycylate)**
ENEMA / RECTUM
site of action
Rowasa = Enema
@Descending Colon + Rectum
Give at bedtime + lay on LEFT SIDE for 8 hours
Canasa = Suppository
@ Rectum
need Bowel Movement first
Which Mesalamine Formulation(s) acts on:
TERMINAL ILEUM+Colon
“LAD” -> Ileum
Lialda
1200mg Tab
Asacol HD
800mg Tablet
Delzicol
400mg Cap
ADR of all Mesalamines = Diarrhea @ initiation
Which Mesalamine Formulation(s) acts on:
JEJUNUM + Colon
APRISO
375mg Cap
APRISO -> JEJUNUM
Which Mesalamine Formulation(s) acts on:
SMALL BOWEL + Colon
PENTASA
250mg / 500mg
- *PENTA = A LOT
- -> ENTIRE SMALL + LARGE COLON**
5-ASA = Mesalamine
HyperSensitivity vs Allergy
Allergy:
Worsening of Colitis
Diarrhea / Bleeding / Ab Pain / Fever / HA / Rash
D/C and Document as ALLERGY
Hypersensitivity
should be D/C’d IF:
Pancreatitis / Pneumonitis / Nephrotoxicity
SULFASALAZINE
MONITORING
Sulfapyridine = Haptotoxicity + Blood Issues
CBC
LFTs
@initiation of therapy
q2weeks for 3 months
q1month for 3 months
every 3 months
5-Asa = Mesalamine
MONITORING
SCr
@6weeks / 6 months / 12 months
Use caution in patients with renal insufficiency
CorticoSteroids
IBD INDICATION?
MoA
Treatment of: ACTIVE UC or CD
MODERATE-SEVERE disease who require RAPID improvement
SEVERE-FULMINANT disease who face surgery
FAILED 5-ASA therapy
- HAS NO ROLE AS MAINTANENCE*
- ineffective at MAINTAINING remission + side effects*
MoA: Potent Anti-Inflammatory Agent
Budesonide
Entocort / Uceris
IBD Indication
Preferred Steroid if:
- *MILD-MODERATE** symptoms
- *LONG-TERM steroids are required**
Due to extensive 1st pass metabolism:
- **_LOW systemic BIOavailability
- -> MINIMIZE SYSTEMIC SIDE EFFECTS_***
UCERIS
Budesonide
Formulation / Indication / Target Location
9mg Oral Tablet + RECTAL FOAM
- *Active Mild-Moderate UC**
- UC-eris*
Targets:
COLON
Rectal formulation:
40cm from Anal Verge
Entocort EC
Budesonide
Formulation / Indication / Target Location
3mg ORAL capsule
Active CD
Maintanence of Remission CD
Targets:
Terminal Ileum + Ileum + Ascending Colon
AZA & 6-MP
ImmunoModulators for IBD
Indication / Onset / ADR
Not FDA Approved:
Used for STEROID-SPARING Effect as Maintenance Agents
combined w/ BIOLOGICS –> REDUCE IMMUNOGENECITY
since the Biologic can mount an immune response
3-6 months
ADR:
- AVOID IN YOUNG MALES* due to Hepatosplenic T-cell Lymphoma
- *Hepatotoxicity** (6-MMP)
- *Bone Marrow Supression** (6-TGN)
- *Infxn / Pancreatitis / GI disturbances / MALIGNANCY**
Which IBD Drug should we avoid in
YOUNG MALES?
AZA** / **6-MP
ImmunoModulator Therapies
BBW –> Hepatosplenic T-Cell Lymphoma
in Young Males
Crohn’s Disease
COMPLICATIONS
- Fistulas– 40%
- Abscesses
- Fissures (ulcer)
- Nutritional deficiencies – can’t absorb / weight loss
- Obstruction
- Stricture – hard to pass
- Intestinal resection – 60-80%
Which IBD Drug
requires TPMT enzyme activity test?
AZA** / **6-MP
Immunomodulator Therapies
TPMT –> 6-MMP = Hepatotoxic Metabolites
Deficient / Homozygous <4 = AVOID AZA
Low / HETERozygote 4-12 = Reduce dose by 50%
Methothrexate
What needs to be MONITORED during THERAPY?
CBC** + **LFTs
weekly 1x month –> Monthly 3mo –> q 3 month
CBC = Bone Marrow Suppression
LFT = Hepatotoxcity
PULMONARY FIBROSIS
= unique ADR
Also is TERATOGENIC
AZA & 6-MP
What needs to be MONITORED during THERAPY?
CBC** + **LFTs
weekly 1x month –> Monthly 3mo –> q 3 month
CBC = Bone Marrow Suppresion from 6-TGN
LFT = Hepatotoxcity from 6-MMP
6-TGN** & **6MMP
levels if patient is NOT responding
CSA + FK (Tacrolimus)
ImmunoModulators for IBD
Indication / Onset / ADR
Not FDA Approved for IBD:
used for SEVERE, Treatment-Refrectory Colitis (primarily UC)
5-14 days (slow still, but faster)
IV Continuous Infusion
ADR:
Nephrotoxicity / HT / Paresthesia
Metronidizole / Ciprofloxacin
Antibiotics for IBD
Indication / Onset / ADR
only as ADJUNCTIVE therapy
used only if they have an infxn or @risk
Indications:
- *CD + Abscess or Fistula**
- *Intestinal or Perianal Disease** or Pouchitis
concern is C.DIFF
ADR:
Metronidazole = Neuropathy / Metallic Taste / Disulfram Rxn
Cipro = Tendon rupture, esp w/ high dose Steroids
Methotrexate
ImmunoModulators for IBD
Indication / Onset / ADR
Not FDA Approved for IBD:
Used for steroid Sparing effect as a Maintenance agent
Combine with BIOLOGICS to reduce immunogenecity
2-8 weeks (slow)
IM/SC + Folic Acid
ADR:
PULMONARY FIBROSIS
Hepatotoxicity / Bone Marrow Suppression
Infection
GOLIMUMAB
Brand / Class / Indications / Administration
Simponi = Human
Anti-TNFa
UC ONLY
SC dosing
CERTOLIZUMAB
Brand / Class / Indications / Administration
Cimzia = Peg-human
Anti-TNFa
- *CD ONLY**
- *C**imzia / Certolizumab
SC dosing
ADALIMUMAB
Brand / Class / Indications / Administration
Humira = Human
Anti-TNFa
CD & UC
SC dosing
INFLIXIMAB
Brand / Class / Indications / Administration
REMICADE = Chimeric
Anti-TNFa
CD & UC
Weight Based dosing:
IV
Anti-TNF-a ADRS
Infliximab / Adalimumab / Certolizumab / Golimumab
Can worsen CONGESTIVE HEART FAILURE = CHF
dose related - avoid 5mg/kg> of infliximab w/ HF
Hepatotoxicity - LFTs
Bone Marrow Suppression - CBC
- *Infections**
- *TB** / herpes / PCP / HEP B
Injection / Infusion site RXNs
BBW = Lymphomas
Anti-TNFa MONITORING
Infliximab / Adalimumab / Certolizumab / Golimumab
@Initiation
- *TB / Hep B**
- *CBC / LFT**
Q3 months = CBC / LFT
Annually = TB / Hep B
TREAT TB b4 INITIATING THERAPY
2 months prior to starting
Anti-TNFa
THERAPEUTIC DRUG MONITORING = TDM
Infliximab / Adalimumab / Certolizumab / Golimumab
TDM occurs in LOSS of RESPONSE to therapy
or after a DRUG HOLIDAY
Monitor Trough Levels, immediately prior to next dose
Drug Levels
correlate with longer remission + better endoscopy scores
Anti-Drug Antibodies = ADA
decrease efficacy // increase infusion / admin rxns
can develop with anti tnf after prolonged use
Primary Non-Responder
AntiTNFa for IBD
- *First time Trying –> NO RESPONSE**
- *High TDM Trough level** but no response
Factors:
long disease duration > 2 years
Small bowel extent of disease
smoking / normal CRP levels
60% of patients will respond to another ANTITNFa
Immunomodulator + Anti-TNFa
Indication for IBD
- *FIRST LINE THERAPY** for
- *Moderate - Severe CD**
Consider DUAL therapy based on Patient Factors
for Mild-Moderate CD or UC
Immunomodulator + Anti-TNFa
Combo for IBD
Positives / Negatives
Positives:
Reduces ANTIBODY formation
Increases / maintains - serum drug concentrations
Decrease serum drug clearance = Better Patient Outcomes
Negative:
INCREASED CHANCE FOR LYMPHOMAS + CANCERS
VEDOLIZUMAB
Brand / Class / Indications / Administration
Entyvio
Leukocyte Adhesion Inhbitor
aka Anti-integrin Molecules
BOTH CD + UC
First Line (prior to Anti-TNFa)
Preffered in patients with IMMUNE CONDITIONS
due to Gut selectivity –> avoids systemic immunosuppression
IV dosing
Which IBD Drug is preferred in patients with:
IMMUNE CONDITIONS?
Organ Transplant / Malignancy
- *VEDOLIZUMAB** = Entyvio
- *Leukocyte Adhesion Inhibitor** for BOTH CD +UC
Due to:
- *GUT SELECTIVITY**
- avoids systemic immunosuppresion*
NATALIZUMAB
Brand / Class / Indications / Administration
Tysabri
Leukocyte Adhesion Inhibitors
CD - Only
Inadequate / can not tolerate Anti-tnf
IV only
VEDOLIZUMAB
MoA / ADRs
CD & UC
Binds a4/b7 SELECTIVE for GUT
- *Anti-Integrin molecule** -
- > reduces leukocyte infiltration & inhibits inflammation
ADR:
- does NOT need to monitor TB / HEP B*
- *HA / Nasopharyngitis**
- lower risk of MALIGNANCY / INFECTIOn*
NATALIZUMAB
MoA / ADR
- *CD only**
- *Anti-Integrin** –> acts on CNS & Gut-Trophic T-cells
BBW** = **PML
Progressive Multifocal Leukoencephalopathy
due to non-selectivity for GUT
REQUIRES REMS-TOUCH PROGRAM
ADRs:
Infections / Hepatotoxicity / abnormal WBC
USTEKINUMAB
Brand / Class / Indications / Administration
Stelara
Anti-IL-12 / Anti-IL-23
ONLY CD
Moderate - Severe
for those intolerant of immunomodulators or AntiTNF-a
Weight Based Loading dose = IV
+
Maintance Dose = 90mg SC
USTEKINUMAB
ADR / Monitoring
- *DRUG-DRUG INTERCTIONS**
- *CYP substrates**
TB Test @ Initiation + Yearly
CBC @Baseline + Q3Mo
ADRs:
Reactivation of TB // Infections
Malignancy / HA / Fatigue / Inj Site Rxn
TOFACITINIB
Brand / Class / Indications / Administration
Xeljanz
JAK Enzyme Inhibitor
prevent gene expression of Cytokines & activity of immune cells
for UC only
Moderate - Severe
- *ORAL DOSING**
- no immunogencity = small molecule*
TOFACITINIB MONITORING
JAK Inhibitor for UC only
LIPIDS** / **HERPES ZOSTER INFXN
CBC
Hep B** + **TB Test
CYP3A4 DRUG INTERACTIONS
avoid inducers
(need Shingrix)
TOFACITINIB ADR’s
JAK Inhibitor for UC only
Reactivation of:
TB / Hep B / Herpes Zoster
ask about shingrix
Nasopharyngitis / Dyslipidemia
Infection / HT / Malignancy
UC Treatment
Induction / Maintenance
CD Treatment
Induction / Maintenance
