IBS/IBD Flashcards
what is IBS?
Idiopathic chronic relapsing disorder with abdominal discomfort and change in bowel habits
What is the goal with txt of IBS?
relieve symptoms (constipation, diarrhea, abd pain/bloating) and improve bowel function -we don't know what causes it so we just txt symptoms
IBS is a chronic ____ not a chronic _____ condition. what does this mean for us when txting it?
chronic relapsing not chronic progressive
- although we want to give comfort, careful with meds as risks can outweigh benefits (b/c we’re not decreasing morbidity/serious complications with our treatment anyways)
IBS what are some examples of food triggers vs natural fiber sources ?
food trigger example: raw veges, caffeine, carbonation, fructose and sorbitol
natural fiber example: Beans (navy, kidney, pinto); broccoli, celery, apples, pears, strawberries
_______ can improve abdominal pain and global symptoms
They may be considered for patients with moderate to severe symptoms
anti-depressants
three main categories of IBS
constipation, diarrhea, abdominal pain/bloating
all three kinds of mild IBS are treated with ?
education, stress management, diet and exercise
moderate IBS-C txt options
Osmotic Laxative: Polyethylene glycol (Miralax)
severe IBS-C txt options (2)
Prescription Laxative:
- Chloride Channel Activator : lubiprostone
- Guanylate Cyclase-C Agonist: linaclotide, plecanatide
moderate IBS-D txt options (2)
Antidiarrheal Agent:
- Loperamide
- Bile Acid Sequestrants
severe IBS-D txt options: (2)
Antibiotic : rifaxamin
5-HT3 antagonist : Alosetron
moderate IBS- abd pain/bloating txt options (3)
Antispasmodic:
- Peppermint oil
- Dycyclomine
- Hyoscyamine
severe IBS-abd pain/bloating txt options (2)
- TCAs: Amitriptyline
2. SSRIs: -cytalopram and fluoxetine
3 groups of drugs we can use for IBS
antidepressants, antispasmotics, probiotics
antidepressants can be used for ____
while antispasmotics can be used for _____
both txt abdominal pain but in addition…
antidepressants: global symptoms
antispasmodics: acute attacks of pain or before meals for postprandial symptoms
what two probiotics can we use for IBS?
(lactobacillus & bifidobacterium)
what can probiotics do for IBS?
Reduces IBS symptoms
Improve abdominal pain, bloating, flatulence
Help to restore normal GI flora
IBS D&C w/ abd pain: txt as a ____ syndrome . first line and second line drugs?
chronic pain
first line: antidepressants (TCAs)
second line: antidepressants (SSRIs)
what TCA-antidepressant do we go to for IBS D&C w/pain? what properties of this drug are helpful for this kind of IBS and how?
Amitriptyline
-Anticholinergic properties of TCA are helpful at decreasing motility & GI secretions without affecting mental status
dosage of TCAs (Amitriptyline) for IBS?
-Low dosage (10-50mg for IBS vs 150mg or more for depression) decreases adverse effects
what are the SSRIs we use for second line IBS D&C w/ pain?
Paroxetine (Paxil); Citalopram (Celexa); Fluoxetine (Prozac)
the_______ are anticholinergics
antispasmodics
what are the 2 antispasmodic drugs we use?
Dicyclomine (Bentyl)
Hyoscyamine (Levsin)
(“mine”)
MOA of anti-spasmodics?
Inhibiting muscarinic input in the enteric plexus & on smooth muscle
Decreases contractility of intestinal smooth muscle
peppermint oil can be useful for what kind of IBS? what are the 2 products we can use?
IBS D&C w/ abd pain
pepogest and IBgard
MOA of peppermint oil products (pepogest and IBgard)?
Blocks calcium channels causing relaxation of GI smooth muscle
pepogest and IBgard: take ____ a day. when?
3 times a day (before meals)
5 drugs utlized for IBS w/ diarrhea
Loperamide (Imodium) - anticholinergic, opiod binding
Diphenoxylate (Lomotil) -anticholineric and opiod binding- combined with atropine b/c potential for abuse
Rifaximin (Xifaxan)
Eluxadoline (Viberzi)
Alosetron (Lotronex)
*however, diarrhea often gets better on its own. so question whether these are really needed/helpful
MOA of Rifaximin (Xifaxan)
Inhibits bacterial RNA synthesis by binding to bacterial DNA-dependent RNA polymerase
Abs and excretion of Rifaximin
Minimally absorbed, eliminated unchanged in feces
what do we use Rifaximin for?
IBS w/ diarrhea
Patients see improvements in IBS symptoms and bloating
MOA of Alosetron (Losenox) ?
Inhibit 5-HT3 receptor to decrease pain sensation from gut to spinal cord, inhibit motility & increase transit time of bowel.
End result decrease nausea, bloating, pain, and diarrhea
which drug…
“Approved for IBS with severe diarrhea
AND Reserved for women with severe, chronic IBS-D that is unresponsive to other drugs “
Alosetron (losenox) - a 5HT3 inhibitor
- (dont really know why only women- but men wont generally be prescribed it)
ADRs Alostetron (Losenox)?
rare but significant - constipation requiring hospitalization and ischemic bowel- sometimes fatal
what is the REMS policy?
means a drug is only prescribed by those with special training. This is in regards to Alostetron for IBS as the ADRs are significant and dangerous.
MOA of Eluxadoline (Viberzi)
- Mu & Kappa opioid receptor agonist
Leads to decreased muscle contractility
Inhibition of water and electrolyte secretion
Increase rectal sphincter tone - targets Delta opioid receptor antagonist
Reduce iatrogenic constipation and abdominal pain
what drug do we use for IBS w/ diarrhea that targets ALL components of the opiod receptor? what schedule of controlled substances is this?
Eluxadoline (Viberzi)
- a schedule IV controlled substance
Eluxadoline (viberzi) is contraindicated in pts w/…
Contraindicated in patients with biliary duct, pancreatic duct, or GI tract obstruction
ADRs of eluxadoline (Viberzi)
going to far on the anti-diarrheal
zofran for IBS
Also a 5HT3 receptor antagonist
only helps with IBS diarrhea (can be very constipating), no help with abdominal pain.
bile acid sequstrants for IBS
Cholestyramine (Questran)
May increase colonic transit time and improve IBS symptoms
*these are also use for cholesterol
what is our first choice agents for IBS-C (mild)?
bulk forming agents: reduce strain and soften stools
what are the bulk-forming agents? (4)
Psyllium (Metamucil); Methylcellulose (Citrucel); Polycarbophil (Fibercon); wheat dextrin (Benefiber)
what can a pt take if bulk-forming agents aren’t working for IBS-C?
- osmotic Lax (polyethylene glycol aka miralax) - ok for longterm use
- Cl- Channel activators or GCC agonists
can also use… Stood softeners (docusate); colonic stimulants (bisacodyl, senna)
what Cl-channel activator do we use for severe IBS-C?
Lubiprostone (Amitiza)
what GCC agonist do we use for severe IBS-C?
Linaclotide (Linzess) or trulance
Inflamm. bowel disease includes what two disorders
crohns and UC
Inflamm bowel disease: Symptoms can be similar to IBS but have evidence of ______, ______ and _______.
What contributes to the ongoing inflamm. process?
Symptoms can be similar to IBS but have evidence of bowel inflammation (bleeding, weight loss, elevated inflammatory markers (ESR &CRP) & abnormality on endoscopy or biopsy
- inflammatory CtKs contribute to ongoing inflammatory process (IL-1, IL-6, TNF)
UC vs crohns? where in the gut do they have an impact?
UC- colon
crohns- localized areas all throughout small and large intestine
contributory factors for inflamm bowel disease (Weeds)
genetic association with first degree relatives, defects in intestinal epithelial barrier and immune system, environmental (NSAIDS, smoking, and diet worsen IBD)
what is fulminant IBD?
more severe, abrupt onset - pateint will present more systemically with different symptoms (>10 stools per day compared to mild which is <4 per day)
IBD: how many stools per day: mild, moderate, severe, fulminant
mild: <4
moderate: >4
severe: >6 w/ blood
fulminant: >10 w/ continuous blood
(increasing signs of systemic toxicity starting at moderate)
drugs used for mild IBD
Aminosalicylates
Topical Corticosteroids for proctitis
Budesonide for ileitis
drugs used for moderate IBD
Immunomodulators :
Azathioprine & 6-mercaptopurine
Methotrexate
Cyclosporin
Oral Corticosteroids
TNF inhibitors
drugs used for severe IBD
IV Corticosteroids
Cyclosporine
Integrin Receptor Antagonist
Interleukin 12 & 23 Antagonist
3 additional options for IBD txt?
Antibiotics
Prebiotics
Probiotics
what are aminosalicylates used for?
Used for the induction and maintenance of remission in mild to moderate ulcerative colitis and Crohn’s disease
Contain 5-aminosalicylic acid (5-ASA) -mesalamine
two types of aminosalicylates
Mesalamine (5ASA)
Azo compounds
5 ASA works ______ in GI tract with ______ absorption. Therefore…
work topically in GI, with little systemic Abs.
therefore not many ADRs( except one), but also dont have anti-inflammatory activity once they are absorbed
which 5ASA has significant ADRs and what are they?
Sulfasalazine (one of the azo compounds)- Only azo compound broken down into 5ASA (Mesalamine) and an ACTIVE component- sulfapyridine.
Rash and fever Hepatitis AGRANULOCYTOSIS Pancreatitis Reversible oligospermia (decreased sperm production)
proposed MOA of 5 ASAs (Weeds)
Thought to inhibit prostaglandin and Leukotriene synthesis and inhibit TNF
Why are brand names important for the 5ASA-(Mesalamine) agents? what are the different brand names?
brand name is more important than usual b/c it means a different formulation. (released in colon at different times based on pH )
- Pentasa
- Asacol
- Lialda
- Rowasa/Canasa
(RC PAL)- Rectal Colon & pals
Mesalamines:
Avoid administration with antacids because they ______ and ______.
Similar interaction could occur with _____ and ______.
change stomach pH and cause premature dissolution of coating.
PPI and H2-receptor antagonist
What are the significant differences in the different 5 ASA (Mesalamines)? (pentasa, asacol, lialda, rowasa/canasa)
Pentasa: oral extended time release: releases throughout the small intestines and colon.
Asacol & Lialda: pH dependent resin: ileum to proximal colon/rectum
Rowasa or Canasa: enema and suppository; works topically on rectum and sigmoid colon
what are the three different 5ASA- Azo compounds? and of the three which is broken down into 5 ASA and an active compound?
“Salazines”
Sulfasalazine (Azulfidine) breaks down into 5 ASA and sulfapyridine
Olsalazine (Dipentum) breaks down into 5-ASA & an inactive compound
Balsalazide (Colazal)- 5-ASA & inactive compound
Azo compound MOA
5ASA bound to another molecule to allow passage through the small intestine
When the azo compounds reach the terminal ileum & colon broken down by an enzyme found there called azo reductase
Overall: works only througout Colon (proximal to rectum)
what is the pH range from jejunum, through small intestine, colon, to rectum?
jejunum around 6.5 .. gets gradually more neutral…
distal colon and rectum around 7
When do we use topical glucocorticoids for IBD?
mild to moderate UC and Crohn’s
-for acute flares,not useful for maintaining disease remission.
what are the topical glucocorticoids that we use for IBD?
Hydrocortisone enemas, foam or suppositories, topical budesonide
what are the major benefits to using topical glucocorticoids?
maximize local tissue effect & minimize systemic absorption
what is a special, powerful glucocorticoid
About 15 times more potent than prednisone?
budesonide
when changing from prednisone to budesonide, allow for a ____ overlap. why?
2 week.
b/c of HIGH first pass metabolism of budesonide, it wont be biologically available until 2 weeks. (good for little systemic effect)
what are the two formulations of budesonide that we use for IBD? what do we use each for?
Entocort EC (oral) is for mild to moderate Crohn’s involving the ileum and/or ascending colon
Uceris (oral & rectal foam) if for mild to moderate ulcerative colitis
what are the 4 immunomodulatory agents for IBD?
Azathioprine & Mercaptopurine
Methotrexate
Cyclosporine
Tacrolimus (Prograf)
MOAs of the immunomodulatory agents for IBD? (Azathioprine/mercaptopurine, methotrexate, cyclosporine, tacrolimus)
Azathioprine & Mercaptopurine: inhibits purine synthesis. anti-proliferative effects and induce t-cell apoptosis
Methotrexate: inhibits DNA synthesis. repair and cellular replication contributing cell death
Cyclosporine: inhibits production & release of IL-II and prevents IL-II activation of T-lymphocyctes
Tacrolimus (Prograf) : same as Cyclosporine ?..
which drug can we use for moderate/ severe steroid dependent and steroid resistant crohns?
methotrexate (an immunomodulatory agent)
which drug can we use for severe steroid dependent and steroid resistant UC?
cyclosporine
or maybe tacrolimus
For methotrexate, what is the dosing?
once a week! if they take more than once a week it cacn be deadly (even if they’re breaking up a dose between days)
major ADR for azathioprine and mercaptopurine?
hepatotoxicity and myelosuppression (bone marrow suppression)
what are the 4 TNF-Alpha antagonist agents for IBD? when do we utilize these?
Infliximab (Remicade) Adalimumab (Humira) Certolizumab (Cimzia) Golimumab (Simponi) Used for moderate to severe ulcerative colitis and/or Crohn’s not responsive to conventional therapies ( A STEP UP THERAPY, NOT FIRST CHOICE)
what does TNF-alpha normally do? (aka why do we want to antagonize it?) (weeds)
TNF-α causes release of proinflammatory cytokines from macrophages, t-cell activation, leukocyte migration
ADRs of TNF alphas
Infusion reactions, increased risk for serious infections (TB, fungal infections, opportunistic infections (legionella & Listeria);bone marrow suppression, reactivation of hepatitis, heart failure exacerbations
(significant but Cleveland did not highlight in class)
What are the two integrin receptor antagonists for IBD? when do we use these?
Natalizumab (Tysabri)
Vedolizumab (Entyvio)
- b/c of rare but significant ADRs, we only use these as a last resort
MOA of natalizumab and vedolizumab?
ALPHA-4 INTEGRIN ANTAGONIST:
Alpha-4 integrin is on leukocytes that mediates adhesion to endothelial receptors and migration into the intestine
BLOCKING THIS REDUCED INFLAMMATION
what are integrins?
Integrins are cell adhesion molecules and help leukocyte infilatration .
for any biologic, it is important to test for _____ prior to prescribing.
TB, as these can cause reactive latent TB
ADRs of natalizumab and vedolizumab?
rare hepatic toxicity & progressive multifocal leukoencephalopathy (PML)- a demyelinating disease causing leisons due to polyomavirus
(rare but significant)
what is the IL- 12 &23 antagonist ?
Ustekinumab (Stelara)
MOA of Ustekinumab (weeds)
Biological effects of IL-12 and IL-23 include natural killer (NK) cell activation, CD4+ T-cell differentiation and activation.
Binds to and blocks IL 12 & 23 preventing activation of inflammatory and immune response
when would we use ustekinumab?
Used for moderately to severely active Crohn’s disease in adults who were intolerant/unresponsive to immunomodulators, steroids or TNF inhibitor
ADRs of ustekinumab? (major ones) (weeds.. maybe)
vulvovaginal candidiasis, TB, non-melanoma skin cancer
what three Abx may we use for IBD? why would we look to use these?
- metronidazole (flagyl)
- ciprofloxacin (cipro- a fluoroQ)
- Rifaximin (Xifaxan)
Bacteria plays role in IBD and ABX treatment helpful, particularly in Crohn’s
what bacteria do each of the Abx treat? (flagyl, cipro, rifaximin)
(weeds)
flagyl: anaerobic
cipro: gram + and gram -
rifaximin: gram + and gram -
which Abx do we NOT want to use longterm?
flagyl
which Abx has significant ADRs and which has none?
bad: Cipro (tendon rupture, QT prolong, hypoGlyc.)
good: Rifaximin (acts locally in gut)
what is our general approach to IBD treatment?
- Identify Severity: Active (mild to fulminant) or remission
- Determine extent and location of disease
- pick a drug based on … (4 criteria)
4 Criteria for IBD drug
Onset of action
Formulation (topical, oral, parenteral)
Effectiveness
Potential adverse effects or contraindications
IBD txt recommendation: mild-moderate Crohns
Aminosalicylate or Budesonide (ileal) +/- topical
Left sided: Enema
Rectal: Suppository
IBD txt recommendation: mild-moderate UC
Aminosalicylate or Budesonide +/- topical
Left sided: Enema
Rectal: Suppository
IBD txt recommendation: moderate- severe Crohns
- TNF-⍺ inhibitor with
Azathioprine/6-MP or methotrexate
+/- - Corticosteroids (short-term)
- Vedolizumab or Natalizumab (last line)
IBD txt recommendation: moderate- severe UC
1. TNA-⍺ inhibitor \+/- 2. Azathioprine/6-MP \+/- 3. Corticosteroids (short-term)
- Vedolizumab (last line)
ADR: TNF alpha antagonist
Infection Risk (screen for TB/Viral Hepatitis)
Risk of Heart Failure or exacerbation
Hepatosplenic T-cell lymphoma when used with azathioprine or 6-MP in young male patients
Antibody formation
Infusion reactions
ADR: anti motility agents
Risk of toxic megacolon in active disease
ADR: Azathioprine/6-MP
Bone marrow suppression, pancreatitis, hypersensitivity
Check TPMT activity (poor metabolizer = ↑ drug concentration
Lymphoma when combined with TNF-⍺ inhibitor
ADR: Methotrexate
Bone marrow suppression, pulmonary and hepatic toxicity
Pregnancy - teratogen
ADR: corticosteroids
Adrenal suppression, metabolic effects, infection
ADR: natalizumab & vedolizumab
Progressive multifocal leukoencephalopathy (PML)
