GI Agents: IBS, IBD Flashcards
IBD stands for what?
Inflammatory bowel disease
IBS stands for what?
Irritable bowel syndrome
Two conditions of IBD?
CD: Crohn’s, UC: Ulcerative colitis
IBS-C stands for what?
IBS w/ consipation
IBS-D stands for what?
IBS w/ diarrhea
Crohn’s disease affects which part of the GI tract?
Any part of the GI tract (mouth to anus)
*Most often: portion of SI before LI/colon
Ulcerative colitis affects which part of the GI tract?
LI (colon) and rectum
Non-pharm tx for IBD?
Nutrition, Surgery
Nutrition recommendations for IBD?
-Eliminate foods that exacerbate disease sx (pt. specific, do not restrict wide range w/o evidence)
-Enteral nutrition if possible
-Parenteral nutrition only when bowel rest needed
-Probiotics studied
What can enteral nutrition help facilitate?
Remission induction
Conditions that can require parenteral nutrition?
failed enteral, perf, vomiting, short bowel synd., severe stenosis
Probiotics contain what bacteria?
Non-patho E. coli, bifidobacteria, lactobacilli, S. thermophilus
Colectomy rate for UC?
0.55-20% (wide range)
*can be curative
10 year cumulative risk of surgery for CD?
40-50%
Indications for surgery for IBD?
Complications (fistulas), Uncontrolled disease even w/ max therapy, Long standing disease (8-10 yrs), Prophylactic measure against colon cancer
Surgery in CD cases results in what?
High rates of recurrence
First line tx for mild-severe UC?
Mesalamine (aminosalicylates)
aka 5-ASA’s
Are 5-ASA’s effective for CD tx?
Less effective, can be trialed for mild-mod disease
Absorption of 5-ASA’s?
Rapidly/completely in SI, poorly in colon
Drug formulations of Mesalamine are designed for what?
Delivery to the affected areas of the GI tract/prevent premature absorption
Mesalamine products differ by what?
Areas of bowel where drug is released & Frequency of dosing
Mesalamines and pregnancy?
Fetal malformations not observed
Common ADR’s of Mesalamines?
N/V, headache
Formulation and site of action of Sulfasalazine?
IR & enteric coated tabs
Act @ colon
Formulation and site of action of Rowasa (Mesalamine)?
Enema
Acts @ Rectum-distal colon
Formulation and site of action of Canasa (Mesalamine)?
Suppository
Acts @ Rectum
Formulation and site of action of Asacol (Mesalamine)?
Coated in pH resin (dissolves at pH 6-7 in distal ileum/colon)
Acts @ Rectum-Ileum
Formulation and site of action of Pentasa (Mesalamine)?
Timed-release microgranules in SI
Acts @ Rectum-Jejunum
**widest distribution of action
Formulation and site of action of Lialda (Mesalamine)?
Coated in pH resin (dissolves in colon)
Acts @ Colon
Formulation and site of action of Apriso (Mesalamine)?
Coated in pH resin (dissolves at pH 6-7 in distal ileum/colon)
Acts @ Colon
Formulation and site of action of Balsalazide?
Azo compound
Acts @ Colon
Formulation and site of action of Olsalazine?
Azo compound
Acts @ Colon
Avoid what med w/ sulfa allergy?
Sulfasalazine
Composition of Sulfasalazine?
Sulfonamide moiety (sulfapyridine) and Mesalamine (5-ASA) joined by diazo bond (reduced absorption w/ PO) in same molecule
First line tx for UC and CD?
Sulfasalazine
Pregnancy w/ Sulfasalazine?
Folate supplement recommended w/ use d/t sulfa component
Common ADR’s of Sulfasalazine?
N/V, headaches, rash, anemias
Severe ADR’s of Sulfasalazine?
Hepatotoxicity, thrombocytopenia, nephrolithiasis
Use of corticosteroids in acute to mod-severe UC and CD?
Induce remission
ROAs for corticosteroids in IBD?
PO, PR, IV
Common ADRs of corticosteroids for IBD?
Hyperglycemia, infections, electrolyte disturbances
Long-term ADRs of corticosteroids for IBD?
Osteoporosis, HTN, myopathy, dyslipidemia, adrenal (HPA axis) suppression
Use of corticosteroids w/ pregnancy?
Ok for acute flares, avoid maintenance therapy
**Prednisone preferred
**Avoid Dexamethasone
Budesonide (corticosteroid) use for IBD?
PO controlled release for terminal ileum or colon depending on product
Extensive first-pass metabolism of Budesonide minimizes what?
Systemic exposure (designed for longer term use/less side effects)
Immunomodulator meds for IBD?
Azathioprine, Mercaptopurine, Methotrexate, Cyclosporine
Indication for Immunomodulator meds for IBD?
Patients who:
-fail 5-ASA tx
-refractory or dependent on corticosteroids
Immunmodulators can be used as preferred therapy along w/ which meds for mild-mod CD in the terminal ileum/ascending colon?
Prednisone or Budesonide
Immunmodulators can be used in conjunction w/ what meds for IBD?
Mesalamine derivatives, Corticosteroids, TNF-a agonsists
How long should immunmodulators be used in IBD before benefits are observed?
Extended periods of time (a few weeks - 12 months)
Long-term use of immunmodulators for IBD may be associated w/ risk of developing what?
Significant adverse effects such as infection and lymphoma
Azathioprine (AZA)/Mercaptopurine (6-MP) is what kind of drug?
Immunosuppressant
AZA is a prodrug of what?
6-MP
In patients with TPMT polymorphisms, tx with AZA/6-CMP may require what?
30-70% dose reduction
*genotype or phenotype testing recommended prior to tx
AZA/CMP with pregnancy?
Used commonly in IBD without detriment
**continue if current therapy is stable, don’t start as new drug if patient is already pregnant
Common ADRs of AZA/6-CMP?
Rash, arthralgia, malaise, nausea, infection
Severe ADRs of AZA/6-CMP?
Bone marrow suppression, pancreatitis, liver dysfunction
*Monitor LFTs,CBC
Methotrexate indications?
Reserved for refractory moderate-severe CD (not used as 1st line for induction)
Mechanism of methotrexate?
Antifolate/immunosuppressive agent
Methotrexate use w/ pregnancy?
KNOWN ABORTIFACIENT (former category X)
**STOP 3 MONTHS PRIOR TO PREGNANCY
Common ADRs of Methotrexate?
N/V, photosensitivity, rash
Severe/long-term ADRs of Methotrexate?
Bone marrow suppression, pancreatitis, hepatitis, pulmonary fibrosis
Short term benefit of Cyclosporine (Neoral)?
Treatment of acute, severe/fulminant UC to avoid colectomy in pts who fail corticosteroids
MOA of Cyclosporine (Neoral)?
Calcineurin inhibitor/immunosuppressant
Cyclosporine (Neoral) use with pregnancy?
Has been used in pregnant pts w/ success, an option for pts w/ severe disease
Are biologics safe in pregnancy?
Generally OK to use
Anti-TNF alpha biologics for IBD?
Adalimumab, Certolizumab, Infliximab, Golimumab
Anti-TNF alpha biologics MOA?
Monoclonal antibodies that bind to endogenous TNF alpha blocks activity
Recommended screening for Anti-TNF alpha biologics for IBD prior to therapy?
HBV, HCV, Varicella, HIV, TB
*avoid reactivation of dormant virus w/ suppression of immune system
Use Anti-TNF alpha biologics for IBD with caution in patients with what?
Heart failure
Janus kinase (JAK) inhibitor biologics for IBD?
Tofacitinib, Upadacitinib
MOA of Janus kinase (JAK) inhibitor biologics?
Inhibit signalling pathway for enzymes that stimulate hematopoiesis & immune cell function (dec. inflammatory markers)
IL-21 and IL-23 inhibitor biologic therapy med for IBD?
Ustekinumab
IL-21 and IL-23 are thought to play a role in what for IBD?
Inflammatory process
Intergrin receptor antagonists biologic therapy med for IBD?
Natalizumab, Vedolizumab
MOA for Intergrin receptor antagonists biologic therapy meds for IBD?
Monoclonal antibodies directed against cell adhesion molecules (inhibit migration of memory T-cells across endothelium into inflamed GI tissue)
Are biosimilars interchangeable with biologics?
No, need specific Rx for biosimilars (same clinical effect but slight structural differences –> manufactured separately)
What is Infliximab (Remicade) for IBD?
Prototype biologic associated w/ most robust clinical data to support its use
Use of Infliximab (Remicade) with pregnancy?
Safe during 1st/2nd trimester, concerns for fetal transfer
Common ADRs of Infliximab (Remicade) for IBD?
Infusion related rxn, infections, rash
50% of patients may lose efficacy for Infliximab (Remicade) after 1 yr of tx for IBD due to what?
Development of antidrug antibodies (immunogenic)
Reason for PPD test before Infliximab (Remicade) for IBD?
The drug causing TB reactivation (C/I in TB)
Dosing of Adalimumab (Humira) for IBD?
Initial high dose to induce remission, then switch to lower dose
Administration of Adalimumab (Humira) for IBD?
(SC) Inject info thigh/lower abdomen (comes in pen - can be injected by pt at home), rotate injection site
Syringes for Adalimumab (Humira), Golimumab (Simponi), and Certolizumab (Cimzia) may contain what?
Latex
ADRs of Adalimumab (Humira) for IBD?
Rash, ADA, injection site rxn, headache, infection
Administration of Certolizumab (Cimzia) for IBD?
(SC) Prefilled syringes and vials (vials must be reconstituted), thigh or abdomen, rotate injection sites
ADRs of Certolizumab (Cimzia)?
Rash, ADA, injection site rx, headache, infection
Warnings for Certolizumab (Cimzia)?
Rare demyelinating CNS disease (optic neuritis, seziures, MS, Guillian Barre)
Golimumab (Simponi) administration for IBD?
(SC) self-administer w/ auto-injector
Monitoring for Golimumab (Simponi) tx for IBD?
CBC w/ diff, Infections, HF
Administration of Tofacitinib (Xeljanz) for IBD?
PO - approved for UC
BBW for Tofacitinib (Xeljanz)?
-Inc. risk of serious infection, cancers, lymphoma
-Inc. mortality & thrombosis risk w/ 10mg dose compared to 5mg of TNF inhibitors (if sx of thrombosis: D/C med and evaluate)
How is Tofacitinib (Xeljanz) available?
Through specialty/network pharmacies
Dosage of Tofacitinib (Xeljanz) for IBD?
Start high & transition to lower
(can go back up higher if response lost)
Baseline labs for Tofacitinib (Xeljanz)?
Lymphocyte, Neutrophil/platelet, Hemoglobin, Lipids, HR & BP
Lab monitoring at 4-8 weeks after starting Tofacitinib (Xeljanz)?
Neutrophil/platelet, Hemoglobin, Lipids
Lab monitoring Q3 months after starting Tofacitinib (Xeljanz)?
Lymphocyte, Neutrophil/platelet, Hemoglobin
Periodic lab monitoring for Tofacitinib (Xeljanz)?
Lipids, HR & BP
Administration of Upadacitinib (Rinvoq) for IBD?
PO
*just approved for CD
BBW of Upadacitinib (Rinvoq) for IBD?
Inc. risk of infections, cancers, thrombosis
Inc. mortality (similar to Xeljanz)
Administration of Ustekinumab (Stelara) for IBD?
Weight-based dose initially IV, then SubQ use every 8 wks
Rare instance of what occurring with Ustekinumab (Stelara) for IBD?
Reversible posterior leukoencephalopathy syndrome (RPLS)
Heterogenous: headache, altered MS, seizures
Administration of Natalizumab (Tysabri) for IBD?
IV every 4 wks
Taper what meds if patient is taking them once response is observed with Natalizumab (Tysabri) for IBD?
Steroids
D/C Natalizumab (Tysabri) for IBD when?
No benefit by wk 12, unable to taper steroids w/in 6mos, steroid use for >3mos of the year
What is required with use of Natalizumab (Tysabri) for IBD?
Patient enrollment in CD TOUCH program d/t adverse effects: all parties must be informed of risks
(restricts use to prescribers, infusion centers, pharmacies involved)
Main risk with use of Natalizumab (Tysabri) for IBD?
Progressive multifocal leukoencephalopathy (PML)
What is Progressive multifocal leukoencephalopathy (PML)?
Assoc w/ exposure to JC virus, occurs in immunocompromised pts, risk increases w/ duration of tx >2yrs/prev use of immunosuppressants/pre-existing anti-JC virus antibodies
Adverse effects of Natalizumab (Tysabri) for IBD?
Headache, fatigue, nausea, hypersensitivity rxn, infections
Administration of Vedolizumab (Entyvio) for IBD?
Induction & maintenance infusion
Infuse over 30 min, observe for infusion rxns
Monitoring with Vedolizumab (Entyvio) for IBD?
LFTs, infection
Adverse effects of Vedolizumab (Entyvio) for IBD?
Headache, arthralgia, antibody development
Patients should be up to date on what when taking Vedolizumab (Entyvio) for IBD?
Immunizations
Do not give live vaccines if patients are taking what meds for IBD?
Biologics
Use of Ozanimod (Zeposia) for IBD?
Option for high risk or mod-severe active UC in outpatients & those w/ UC who are corticosteroid dependent
Mechanism of Ozanimod (Zeposia) for IBD?
Sphingosine 1-Phosphatase (S1P) receptor modulator: inhibits lymphocytes from leaving lymph nodes/migrating to GI tract
Administration of Ozanimod (Zeposia) for IBD?
PO (initial days 5-7 and maintenance day 8)
Adverse effects of Ozanimod (Zeposia) for IBD?
Infection, bradycardia, BP changes (early on: hypotension, later: risk for HTN), macular edema, headache, increased LFTs
C/I of Ozanimod (Zeposia) for IBD?
MI, unstable angina, stroke, TIA, decompensated HF, Mobitz type II second/third degree AV block, sick sinus synd in last 6 mos, sleep apnea, use of MAOI
Considerations with use of Ozanimod (Zeposia) for IBD with pregnancy?
CONTRADINDICATED, use contraceptives during use and 3 months after d/c
Abx use in IBD?
Possible adjunctive therapy, perineal CD w/ fistula, infectious abscess or pouchitis
Abx for IBD?
Metronidazole PO/IV, Ciprofloxacin PO/IV
Long term adverse effects of Abx use for IBD?
abx resistance, predisposition to C. diff, neurotoxicity secondary to metro use
Short term adverse effects of Abx use?
Metronidazole: Nausea, metallic taste, peripheral neuropathy
Cipro: GI upset, QT prolongation, tendon rupture, photosensitivity
Abx use for IBD considerations w/ pregnancy?
Metro: crosses placenta, cleft palate/lip in 1st trimester, may be ok for certain infections
Cipro: no increased major birth defects/miscarriage/adverse maternal outcomes
Nonpharmacologic therapy for IBS?
Diet (avoid exacerbating food-lactose, etc.), Inc. insoluble fiber intake may help w/ IBS-C, Drink 8+ cups of fluid/day
Alternative medicine options for IBS?
Acupuncture, Cognitive-behavioral therapy, Hypnotherapy
Recommended nonpharmacologic/adjunctive therapy for IBS?
Strong recommendations: NO fecal transplant, soluble (NOT non-soluble) fiber
Conditional recommendations: FODMAP diet, NO probiotics, gut-directed psychotherapy, peppermint
Fiber supplements for IBS-C?
Psyllium, Methylcellulose, Calcium Polycarbophil
MOA of Fiber supplements for IBS-C?
Absorbs water to inc. peristalsis
Side effects of Fiber supplements for IBS-C?
Bloating, flatulence (increase dose gradually)
Antidiarheals for IBS-D?
Loperamide and Diphenocylate/atropine
MOA of Loperamide for IBS-D?
Acts on opioid R (antidiarrheal)
Indications for Loperamide for IBS-D?
Diarrhea, urgency, incontinence
Side effects of Loperamide for IBS-D?
Constipation
MOA of Diphenocylate/atropine for IBS-D?
Antidiarrheal that inhibits GI motility and propulsion
Indication for Diphenocylate/atropine for IBS-D?
Diarrhea
Side effects of Diphenocylate/atropine for IBS-D?
Constipation, tachyarrhythmia
Antispasmodics for IBS-D?
Hyoscyamine, Dicyclomine
MOA of Hyoscyamine, Dicyclomine (antispasmodics) for IBS-D?
Anticholinergic agent
Indications for Hyoscyamine, Dicyclomine (antispasmodics) for IBS-D?
Pain, post-prandial urgency
Side effects of Hyoscyamine, Dicyclomine (antispasmodics) for IBS-D?
Xerostomia, urinary retention, tachycardia, anticholinergic effects (drying)
Meds for IBS-D or abdominal pain?
Amitriptyline, Peppermint oil (OTC)
MOA of Amitriptyline for IBS-D or abdominal pain?
Tri-cyclic antidepressant
MOA of Peppermint oil?
Thought to cause smooth muscle relaxation in gut (limited studies)
Indication for Amitriptyline, Peppermint oil (OTC)?
Pain or other discomfort in IBS-D
Side effects of Amitriptyline?
Anticholinergic effects, sedation, orthostatic hypotension, possible wt. gain (start low, inc gradually)
Side effects of peppermint oil (OTC)?
Heartburn, N/V, avoid w/ severe GERD, gallbladder dz, pregnancy
Pharmacologics for IBS-D?
Alosetron, Rifaximin, Eluxadoline
MOA of Alosetron for IBS-D?
Selective 5HT3 R antagonist in gut
MOA of Rifaximin for IBS-D?
Inhibits RNA synthesis
Indications for Rifaximin for IBS-D?
Pain, urgency, diarrhea in IBS-D
Side effects of Alosetron, Rifaximin?
Constipation
MOA of Eluxadoline for IBS-D?
Mixed mu agonist, kappa agonist, delta antagonist on opioid R’s
Take Eluxadoline for IBS-D with what?
Food
Indications for Eluxadoline for IBS-D?
Pain, stool consistency in IBS-D
Side effects of Eluxadoline for IBS-D?
Constipation, nausea, abdominal pain, increased LFTs
Alosteron is only available through what program?
LOTRONEX program d/t side effects
Indications for Alosteron?
ONLY indicated for females w/ sx for >6 months that don’t respond to conventional tx
Warnings/precautions of Alosteron?
C/I in pts w/ hx of constipation, ischemic colitis, intestinal obstruction, Crohn’s, UC, severe hepatic impairment
D/C in pts who develop constipation (ischemic colitis reported w/ fatalities)
Monitoring of pts on Alosteron?
Resolution of sx, Severe constipation
Dose adjustments for Eluxadoline?
Decrease in patients w/o gallbladder
Warnings/precautions w/ use of Eluxadoline?
D/c use w/ constipation >4 days or sphincter Oddi spasms
C/I with pmhx of pancreatitis, alcohol use disorder, liver disease
Monitoring for pts using Eluxadoline?
New or worsening abdominal pain (biliary/pancreatic issues) esp in those w/o gallbladder, LFTs
Pharmacologic agents for IBS-C?
Lubiprostone, Linaclotide, Plecanatide, Tenapanor
MOA of Lubiprostone for IBS-C?
Chloride channel activator
MOA of Linaclotide, Plecanatide for IBS-C?
Guanylate Cyclase Agonist
Indications of Lubiprostone for IBS-C?
Pain, IBS-C in females >18y/o
Indications of Linaclotide, Plecanatide for IBS-C?
IBS-C in adults
Side effects of Lubiprostone for IBS-C?
Diarrhea, headache, nausea, edema, dizzy
Side effects of Linaclotide, Plecanatide for IBS-C?
Diarrhea, flatulence, GI upset
MOA of Tenapanor for IBS-C?
Sodium/hydrogen exchanger 3 indicator
When to take Tenapanor for IBS-C?
Before breakfast and dinner
Side effects of Tenapanor for IBS-C?
Diarrhea
Warnings/Precautions of Lubiprostone?
Pregnancy category C (fetal loss in animal studies)
C/I in known mechanical bowel obstruction
Monitoring for Lubiprostone?
Liver function in hepatic impairment, first dose may cause dyspnea (acute, usually goes away w/ use), K+ (risk of hypokalemia)
Lubiprostone onset?
Can work fast, may have BM within 24 hrs
Warnings/precautions of Linaclotide/Plecanatide?
C/I if known mechanical bowel obstruction
D/C and alert provider if severe diarrhea
Administration w/ high fat meal may worsen diarrhea
Monitoring with Lubiprostone/Plecanatide?
Efficacy (change in bowel movements)
Reserve Tenapanor for what patients?
Pts who have failed other therapy
Warnings/precautions with Tenapanor?
C/I in pts <6y/o
Avoid use in 6-12y/o
Renal impairment may inc. risk of hyperkalemia and diarrhea
Monitoring with Tenapanor?
Frequency of dehydration, K+ in pts w/ renal impairment