IBS/IBD Flashcards
what has Contributing Factors: Genetics, motility factors, inflammation, colonic infections, mechanical irritation to local nerves, stress
IBS
what has Lower abdominal pain, disturbed defecation, and bloating with absence of structural or biochemical explaining factors
IBS
what has -Diarrhea Symptoms > 3 stools/d Extreme Urgency Mucus passage -Constipation Symptoms < 3 stools/wk Straining Incomplete Evacuation -Psychological Depression Anxiety
IBS
what are 3 comorbid conditions with IBS
Fibromyalgia
Functional dyspepsia
Chronic Fatigue Syndrome
MANNING Chronic Or recurrent abdominal pain > __months with 2 or more of the following:
6 mo Ab pain relieved by defecation Ab pain associated with more freq stool Ab distention Feeling of incomplete evacuation after defecation Mucus in stools
ROME III
Recurrent abdominal pain or discomfort > __ days/month in the last __ months associated with 2 or more of the following:
3 days for 3 mo
Relieved with defecation
Onset associated with change in frequency of stool
Onset associated with change in form of stool
for constipation predom IBS how do you treat? 4
Stress management and patient education
Increase dietary fiber and fluid
Next add bulk forming laxative and consider antispasmodics
Add serotonin-4 agonist (Tegaserod)
for diarrhea predom IBS how do you treat? 4
Stress Management and Patient Education
Lactose and caffeine free diet as well as avoiding other causative foods
Add loperamide or another antispasmodic
Add 5-HT3 antagonist (Alosetron)
Mucosal inflammatory condition
Confined to rectum and colon
Ulcerative colitis
Transmural inflammation of GI tract
Can affect any part of GI tract
Crohns
Inflammation is limited to the mucosa; continuous pattern of involvement
UC
what has symptoms of Bloody diarrhea and abdominal pain = cardinal symptoms
Severe cases: fever, anorexia, weight
UC
what has Autoimmune pathophysiology and Inflammation occurs throughout the full thickness of the bowel wall; skip pattern of involvement; strictures, fistulas, ulcers
Crohn’s
what has cardinal symptoms of diarrhea and abdominal pain and Weight loss, vomiting, fever, perianal discomfort, bleeding = common complaints
Crohns
what bacteria 1st detected in 1980s in intestinal tissue of Crohn’s disease pts
Mycobacterium avium subspecies paratuberculosis (MAP)
what bacteria is inc in IBD? and what has no beneifit?
Increase in pathogenic bacteria Bacteroides Escherichia coli Decreased beneficial bacteria Bifidobacterium Lactobacillus species
what is smoking protective in?
UC
what does smoking make worse?
CD
what drugs should you avoid in IBD - 3 types
Opiates Reduce GI Motility NSAIDS Worsen IBD by disrupting mucosal barrier Antidiarrheals Loperamide, Diphenoxylate/Atropine Risk of Precipitating Toxic Megalocolon
what diet improves UC? exacerbates?
NONE
what dietary measure should you avoid in UC exacerbation
fiber
what should you take during remissions of UC
Metamucil 1-2 x day
how do you treat mild to moderate UC - 4 options
-Sulfasalazine 4-6 g/day OR
-Mesalamine 4.8 g/day OR
-Aminosalicylate at dose equivalent to mesalamine 4.8 g/day
-OR if Distal Disease
Mesalamine Enema/Suppository
Corticosteroid Enema
what do you do for remission of mild to mod UC - 2 options
Reduce dose by half OR
With enema/ suppository: Reduce frequency to q 1-2days
what do you use to treat mod - severe UC
Sulfasalazine 4-6g/day OR Mesalamine 3-6g/day
Plus Prednisone 40-60mg/day
how do you treat remitted mod-severe UC
Taper prednisone, then reduce sulfasalazine or mesalamine after 1-2 months to approximately half
how do you treat refractory mod-severe UC? what should you consider if no response
Add Azathioprine or Mercaptopurine (6-MP) OR
Consider Infliximab if no response
how do you treat Severe or Fulminant Ulcerative Colitis?
Hydrocortisone IV
how do you treat remitted Severe or Fulminant Ulcerative Colitis
Change to prednisone add sulfasalazine or mesalamine
if, in Severe or Fulminant Ulcerative Colitis, there is no response for 5-7 days…
Cyclosporine IV 4 mg/kg/day
If no response, patient candidate for colectomy
can surgical resection cure UC?
yes High-grade dysplasia, suspected cancer
Pts with severe disease requiring high-dose steroids that can’t be tapered after 6-12 months
what is used in maintenance of UC? 2 options
Aminosalicylates and/or AZA or 6-MP
Alternative Infliximab 5mg/kg q 8 weeks
what are the nutritional measures for CD? 3
Limit fiber with cramping and diarrhea
Decrease fat intake when steatorrhea
Multivitamin with minerals daily
how do you treat Mild-Moderate Crohn’s if its in ileocolonic or colonic
Sulfasalazine 3-6 g/day or
Oral mesalamine 3-4 g/day
how do you treat Mild-Moderate Crohn’s if its perianal?
Sulfasalazine 3-6 g/day or
Oral mesalamine 3-4 g/day and/or
Metronidazole 10-20 mg/kg/
how do you treat Mild-Moderate Crohn’s if its in the sm bowel?
Oral mesalamine 3-4 g/day or
Metronidazole 10-20 mg/kg/day or
Budesonide 9mg/day
how do you treat mod-severe crohns?
add prednisone to mild-mod
if crohns is refractory or fistulizing
add infliximab
if crohns is not responsive after adding infliximab…
Adalimumab
Natalizumab
Certolizumab
when do you taper prednisone in crohns? and add?
after 2-3 weeks
Add AZA, 6-MP or MTX
how do you treat severe-fulminant crohns?
hydrocortisone IV
how do you treat if severe-fulm crohns doesnt respond to hydrocortisone
Cyclosporin IV
what is first line maintenance for crohns… 2nd and 3rd…
Azathioprine/6-MP
Infliximab 5 mg/kg IV q wk x 6, then q 8 weeks
Methotrexate 25mg IM up to 16 weeks followed by 15mg IM weekly
what is the MOA of Sulfasalazine (Azulfidine)
Metabolized by intestinal bacteria to to the active component 5-aminosalicylate (5-ASA) and sulfapyridine (mesalamine)
what are the contraind of Sulfasalazine (Azulfidine)? 2
Salicylate hypersensitivity
Renal impairment- Monitor SCr
what are the ADRs of Sulfasalazine (Azulfidine)? lots
- N/V, heartburn, anorexia
- HA
- Hypersensitivity rxns (rash, fever)-Do not use in pts with sulfa allergy
- Blood disorders (anemia, thrombocytopenia, granulocytopenia)
- Can impair folic acid absorption
- Idiosyncratic rxns (hepatocellular injury, agranulocytosis, lupus-like phenomena)
- Low sperm counts
what is mesalamine?
aminosalicylate
what are the ADRs of mesalamine?
Local itching and mild rectal irritation with topical enemas
Idiosyncratic rxns: pleuropericarditis, pancreatitis, nephrotic syndrome
how id mesalamine given?
Mesalamine or suppositories for rectosigmoid disease
Delayed release formulations of mesalamine for Crohn’s ileitis
what is the MOA of corticosteroids?
Anti-inflammatory effects
Improves Symptoms
Improves disease severity
how do we taper corticosteroids?
Taper by 5mg/wk prednisone or equivalent
how long should it take for corticosteroids to work?
7-14 days
what does the Inability to taper is indicate
indication for amtimetabolite and/or infliximab therapy
Parenteral steroid indicated in pts …
failing to respond to 7-14 days of high dose oral prednisone or equivalent
what do you need to monitor for in corticosteroids
Glucose intolerance/ metabolic abnormalities
Hyperkalemia
Hyponatremia
glucose
Greater risk for adrenal insufficiency and infections
N/V
Postural hypotension
what is long term tx of corticosteroids? what do you need to do?
> 3 mo bonedensity scan and annual eye exam
what are 2 Immunosuppressives
6-Mercaptopurine (6-MP)
Azathioprine (Imuran)
Pro-drug metabolized to 6-MP
what is the adv of Immunosuppressives
Maintenance therapy that is less toxic than chronic steroid therapy
Steroid-sparing achieve or maintain control and allow reduction or discontinuation of steroids
what is the MOA of Immunosuppressives
Antagonizes purine metabolism; inhibits DNA, RNA and protein synthesis
what is the disadv of Immunosuppressives
delay in onset
what are the numerous ADRs…. BM, other inc risks? GI? Other? Infections?
Bone marrow suppression 2-5% Dose related Managed by dose reduction/withdrawal Leukopenia, thrombocytopenia, pancytopenia Risk of lymphoma 4 fold increase Pancreatitis 1.3-3.3% Dose independent Occurs within 3-4 weeks of start Resolves with stopping drug GI effects N/V, abdominal pain Occurs early, improves with time or with dose reduction Other Fever, rash, arthralgias Dose independent Infections Disseminated CMV, herpes zoster, pneumonia, Q fever, viral hepatitis Occur without leukopenia Increased risk if combined with steroids
what are the drug int of Immunosuppressives
Inhibition of metabolism leading to increased myelosuppression Sulfasalazine, mesalamine Allopurinol Aspirin Furosemid
what is mtx?
immunomodulator
what is the MOA of mtx
Folic acid antagonist with anti-inflammatory effects (affects immune system??)
what is the good thing about mtx
Reduces steroid needs
Improves disease control
what are the adr’s of mtx…. lots!
Nausea Elevated transaminases Leukopenia N/V Hypersensitivity pneumonitis (rare) Hepatic fibrosis Most significant in long term therapy Risk with >1500 mg total cumulative dose and daily dosing DC if moderate/severe fibrosis or cirrhosis found on biopsy
what is contrind for mtx?
Absolute contraindication in pregnancy (Category X)
Stop therapy 3 months prior to conception
Folate supplementation prior to conception
Contraindicated in breastfeeding
what are 2 cyclosporins?
neoral and sandimmune
what is the MOA of cyclosporins
inhibits production and release of IL-2 inhibits activation of T-lymphocytes
what is recommended for cyclosporins in tx? and remission?
Concomitant IV steroids recommended
Cyclosporin alone unable to maintain remission
Requires “bridging” with AZA or 6-MP
Convert IV to PO
PO dose is 2x IV dose
Wean off cyclosporin and steroids over next few months
cyclosporins toxicity?
HTN Hypertrichosis Electrolyte abnormalities Nephrotoxicity Opportunistic Infections Requires PCP prophylaxis
what is the MOA of Tacrolimus (Prograf)
inhibits T-lymphocyte activation
Fungus (streptomyces)
what is ADRs of Tacrolimus (Prograf)
Adverse Reactions: Tend to resolve with dose reductions HA Increased serum creatinine Nausea Insomnia Leg cramps Paresthesias Tremors
what are 3 monoclonal ab?
infliximab, adalimumab, natalizumab
what is the MOA of infliximab?
Monoclonal antibody that binds to TNF-alpha
Inhibits inflammatory cytokines, inhibits leukocyte migration and activation of neutrophils
infliximab contraind?
NYHA class III/IV heart failure Dose should not exceed 5mg/kg in other pts with congestive heart failure Hepatitis Reactivation of hepatitis B Autoimmune hepatitis Discontinue use with LFTs 5x ULN
ab to infliximab what happens?
Increased risk of infusion rxn, shorter duration of response
regularly scheduled less immunogenic than episodic
what infections may infliximab tox cause?
Bacterial, mycosal, mycobacterium
Higher TB rates with more extrapulmonary involvement
what infusion rxn may infliximab tox cause?
During or after (1-2 hrs)
HA, dizziness, nausea, erythema at site, flushing, fever, chills, chest pain, cough, dyspnea, pruritis
Mechanism unclear- not IgE type 1
Doesn’t occur till after 1st infusion; not at every infusion
what delayed hypersensitivities may infliximab tox cause?
3-14 days after infusion
Myalgia, arthralgia, fever, rash, pruritis, dysphagia, urticaria, HA
Resolve spontaneously or require steroids
Prednisone 40mg PO or methylprednisolone 100mg IV 30 min before
what is rare with autoab to infliximab?
Development of drug-induced lupus rare
Reversible with DC
what malignancy may come from infliximab tox?
Malignancy and lymphoproliferative disorder
Longstanding CD and tx with immunosuppression more likely to develop lymphomas
what is the MOA of adalimumab?
recombinant fully-human immunoglobulin-1 anti-tumor necrosis factor (TNF)-alpha monoclonal antibody
what should you do before tx with adalimumab
eval for TB
what is the BB warning on adalimumab
TB, invasive fungal, other opportunistic infections
what are other adrs of adalimumab
Rash, injection site rxn, HA, URI, development of autoantibodies to drug, development of anti-nuclear antibodies (ANA)
Risk of reactivating hepatitis B
what is true aboud natalizumab? approved for? devp for?
Approved by FDA on 1/14/08 for “moderate to severe Crohn’s in pts with evidence of inflammation who have had inadequate response to, or are unable to tolerate conventional therapies
Pts must be enrolled in special restricted distribution program
Crohn’s Disease-Tysabri Outreach Unified Commitment to Health (CD-Touch) Prescribing Program
Originally approved June 2006 for MS
what is the moa of natalizumab?
recombinant immunoglobulin-4 monoclonal antibody
when do you DC natalizumab?
if no response in 12 wks, or steroids not tapered within 6 mo
dont admin natalizumab with?
other immunosuppressants (6-MP, azathioprine, MTX, cyclosporin, or inhibitors of TNF)
what is the major adr of natalizumab?
progressive multifocal encephalopathy
what is metronidazole used for in IBD?
Indications: For treatment of ileocolitis or colitis Failure to respond to sulfasalazine For treatment of abscesses, rectovaginal fistulas, proctocolectomy wounds Low dose maintenance
what are the adrs of metronidazole?
GI upset, metallic taste, paresthesias, antabuse-like rxn
what is cipro for in IBD
Effective in resistant disease when used in combination with standard tx
when do we use metro and cipro in IBD?
Improve and can promote closure of fistulas
Tend to recur once drugs stopped
what opiates are used in IBD? - diarrhea
Diphenoxylate/atropine, codeine, tincture of opium, paregoric, loperamide
