Therapeutics Exam 4 (Inflammatory Bowel Disease) Flashcards
What 2 disease states make up Irritable Bowel Disease (IBD)?
Ulcerative Colitis
Crohn’s Disease
What parts of the body are affected by Ulcerative Colitis (UC)?
Rectum and Colon
-mucosal + submucosal inflammation (more superficial)
-only affects the lower GI tract
What parts of the body are affected by Crohn’s Disease (CD)?
Any part of the GI tract from the mouth to the anus
-Transmural inflammation of any part of the GI tract
-Terminal ileum is most common
-CD normally affects tissue deeper than UC
*Rectal involvement is uncommon
*Perianal disease is common
What physical appearance specific to Crohn’s disease can help differentiate it from other conditions?
Crohn’s disease appears as discontinuous segments of infected bowel with normal bowel separating it
What effect does smoking have on ulcerative colitis?
Potentially protective
-reduced disease activity, fewer flare-ups
What effect does smoking have on Crohn’s disease?
Increases severity
-increased disease frequency and severity
**What is the main drug class that can trigger IBD?
NSAIDs!!!!
patients need to avoid these
-may trigger disease occurrence or lead to flares
Which drug class has a potential association with triggering IBD?
Antibiotics
*causal relationship is unclear
What are the 2 main symptoms of ulcerative colitis?
Diarrhea + Bleeding
-due to mucosal damage and friability
What life-threatening complications are we concerned about with UC?
Toxic Megacolon
Colonic dysplasia/Colorectal cancer (CRC)
note that fistulas and strictures are UNCOMMON
What are the defining features of toxic megacolon?
Severe and potentially fatal complication of UC
-Segmental or total colonic distention (>6cm)
-Acute colitis
-Signs of systemic toxicity
*50% mortality
What complications are we concerned about with Crohn’s disease?
Small bowel stricture
Obstruction
Fistula formation is common
Less bleeding is seen than with UC but anemia is still possible
Carcinoma, but not as likely as with UC
Nutritional deficiency
What is a fistula?
A connection between 2 areas that should not be connected in the body
Which laboratory test for UC correlates with the degree of inflammation present?
Fecal Calprotectin (FC)
How is UC diagnosed?
-Clinical suspicion
-Confirmed by endoscopy (colonoscopy or sigmoidoscopy) and biopsy
-Negative stool examination for infectious causes (Cdiff)
What is hematochezia?
Blood in stool
True or False: IBD can be cured
False, no medications are curative
What are the drug classes used in IBD treatment?
ASAs (aminosalicylates)
Corticosteroids
Immunomodulators (suppressives)
Biologics
Antimicrobials
What drugs are considered aminosalicylates (ASA)?
Sulfasalazine
Mesalamine (5-ASA)
What drugs are considered immunomodulators (immunosuppressives)?
Azathioprine
Mercaptopurine (MP)
Cyclosporine
Methotrexate
What are the two categories of biologics?
Anti-TNF-a
Other
What are the Anti-TNF-a drugs?
Infliximab
Adalimumab
Certolizumab
Golimumab
What are the other biologic drugs?
Natalizumab
Vedolizumab
Ustekinumab
What are the antimicrobial drugs?
Metronidazole
Ciprofloxacin
What are the 2 components of sulfasalazine?
Sulfapyridine + Mesalamine (5-ASA)
-5-ASA is the active compound
-Sulfapyridine is associated with ADR’s!
If sulfapyridine causes ADR’s then why do we not just give mesalamine alone?
We can!
-But it is very rapidly absorbed in the small intestine and giving it alone prevents it from staying in the lumen where it is needed
-But we can use local forms like: enemas, suppositories, or delayed release forms
What area is involved in proctitis UC?
Rectal area
What area is involved in pancolitis UC?
Majority of colon
Which drug form works best for proctitis?
Suppository
Which drug form works best for left-sided disease?
Enema
Which drug form works best for extensive disease + pancolitis?
Systemic tx
What is therapeutic drug monitoring used for?
To determine drug and anti-drug antibody concentrations
What drugs have the most data for therapeutic drug monitoring?
Infliximab
Adalimumab
When should we consider doing therapeutic drug monitoring?
If there is a loss of treatment response
-This monitoring is done reactively, we do not check it to see how the patient is doing
If a patient undergoes Therapeutic Drug Monitoring and has Detectable Antibodies + Sub-Therapeutic Drug Levels, what do we do?
Change to alternate drug in the SAME class +/- immunomodulator
-This is an immune mediated pharmacokinetic failure
-We can still keep the patient on the same drug class especially if they had a good initial response to the original drug
If a patient undergoes Therapeutic Drug Monitoring and has Detectable Antibodies + Therapeutic Drug Levels, what do we do?
Repeat the levels to check for false positive
Switch to a biologic from a different drug class
If a patient undergoes Therapeutic Drug Monitoring and has No Antibodies with Sub-Therapeutic Drug Levels what do we do?
Escalate the dose
If a patient undergoes Therapeutic Drug Monitoring and has No Antibodies with Therapeutic Drug Levels but no response what do we do?
Switch to a biologic from another class
-The patient is just not responding to the drug for an unknown reason
-If they do not respond to one, they probably will not respond to another in the same class
For mild-moderate active UC, if the patient has extensive disease what do we use as first-line therapy?
Oral 5-ASA
Sulfasalazine
Mesalamine
For mild-moderate active UV, if the patient has left sided disease what do we use as first-line therapy?
5-ASA enema
-topical mesalamine enema
For mild-moderate active UV, if the patient has proctitis what do we use as first-line therapy?
5-ASA suppository
-mesalamine suppository
When may a combination of oral and topical options for UC be more effective?
Pts with left-sided/extensive disease
Which monotherapy works better: topical or oral?
Topical typically
If a patient is unresponsive to 5-ASA, what is the next step?
Consider changing the dosage form
If a patient is unresponsive to standard-dose 5-ASA or continues having moderate disease activity, what is the next step?
High dose mesalamine (>3g/day) + Rectal Mesalamine
(combo therapy)
If a patient with mild-moderate UC is refractory to ASA’s what is the next step?
PO corticosteroids
-Budesonide
-Prednisone
Budesonide usage should be limited to what?
<8-16 weeks
When are topical corticosteroids an option? (foams, enemas, suppository)
Distal disease
(ex: left sided, proctitis)
For moderate UC, besides mesalamine, what is the other potential first line option?
PO Controlled Release Budesonide
True or False: 5-ASA therapy is the first-line option for severe UC
No, it is probably not going to be effective
What is the first-line therapy for Severe UC?
Systemic corticosteroids
(po prednisone)
-consider TNF-a inhibitors/biologics
True or False: we should continue 5-ASA therapy in moderate-severe UC patients who achieve remission with biologics/immunosuppressants
FALSE
-do not continue 5-ASA as induction or maintenance in these pts
What are the first-line options for severe UC treatment?
Option 1:
-Budesonide or Prednisone
Option 2 (Treatment Naive):
-Prednisone + Infliximab or Vedolizumab +/- Azathioprine
Option 3 (Previous infliximab exposure):
Ustekinumab to Tofacitinib
What are the first-line treatment options for severe-fulminant UC?
Parenteral Corticosteroids
-methylprednisolone
-hydrocortisone
(IV then po)
Consider TNF-a Inhibitors
-infliximab
Consider cyclosporine or infliximab in pts unresponsive to IV steroids
What drugs should be used for maintenance of remission for UC?
ASA
TNF-a antagonist (infliximab/adalimumab)
Patients who are steroid dependent:
-Azathioprine
-6-MP
-make choice based on what patient has already been started on
Which drug class should not be used to maintain remission in UC?
Corticosteroids
What is the first-line therapy for mild-moderate CD?
Sulfasalazine
-mesalamine has no efficacy
-these drugs do not work super well
What is the first-line therapy for moderate-severe CD?
Systemic corticosteroids
(po prednisone)
-may be more effective than budesonide
If hospitalized:
-IV corticosteroids
(methylprednisolone, hydrocortisone)
Early biologic therapy may be useful
(TNF-a inhibitors)
(combo therapy of infliximab or adalimumab + AZA may be more effective)
What treatment options should we use for severe/fulminant CD?
Parenteral corticosteroids (if no abscess)
-methylprednisolone
-hydrocortisone
Consider infliximab or other biologic if not already attempted
What drug may be preferred for fulminant CD?
Infliximab
-last option before surgery
What drugs can we use for maintenance of remission with CD?
AZA and 6-MP
Methotrexate
TNF-a Antagonists
Vedolizumab, Ustekinumab, Risankizumab
