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Therapeutics IV > Inflammatory Bowel Disease (UC + CD) > Flashcards

Inflammatory Bowel Disease (UC + CD) Flashcards

1
Q

Define inflammatory bowel disease

A

mucosal inflammatory conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract

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2
Q

What are the two types of IBD?

A

ulcerative colitis

crohn’s disease

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3
Q

Define UC

A

mucosal inflammation confined to rectum and colon

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4
Q

Define CD

A

transmural inflammation of GI tract that can affect any part from the mouth to the anus (deeper inflammation)

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5
Q

CD etiology

A

increased Th1 cytokine activity (interferon gamma, interleukin 12 [IL-12])

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6
Q

UC etiology

A

Increased Th2 cytokine activity (IL-13, IL-5)

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7
Q

smoking and UC

A

potentially protective

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8
Q

smoking and CD

A

increased frequency and severity of CD

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9
Q

NSAIDs and IBD

A

doesn’t really cause the disease but can make symptoms worse

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10
Q

Antibiotics and IBD

A

doesn’t really cause the disease but can mess with flora and exacerbate symptoms

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11
Q

UC pathophysiology

A

confined to the rectum and colon and affects mucosal and submucosal layers (its more superficial than CD)

abscess formation in mucosal crypts, coalescence results in ulceration

ulcers can surround normal tissue

mucosal damage –> substantial diarrhea and bleeding

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12
Q

UC complications

A

local, systemic, extraintestinal complications

local: hemorrhoids, anal fissures, perirectal abscesses

Major complications: colonic perforation, massive colonic hemorrhage, colonic structure

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13
Q

UC Toxic megacolon

A

severe and potentially fatal complications

segmental or total colonic distention (> 6cm) with acute colitis and signs of systemic toxicity

increased depth of ulceration

vasculitis and thrombosis

colonic dilation and potential perforation

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14
Q

UC Toxic megacolon symptoms

A

fever, tachycardia, abdominal distention, elevated WBCs, abdominal distention on radiograph

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15
Q

UC pathophysiology: colonic dysplasia/colorectal cancer (CRC)

A

risk of colonic dysplasia w/ transition to CRC is 5x greater in UC

cumulative risk of CRC is up to 20 - 30% at 30 years

Screening colonoscopy with biopsies recommended at 8 years after UC onset and every 1 - 2 years after that

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16
Q

CD pathophysiology

A

transmural inflammation

can occur anywhere in the GI tract

often discontinuous (normal bowel separating diseased bowel)

deep, elongated ulcers, cobblestone appearance

bowel wall injury may be extensive, associated with luminal narrowing

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17
Q

Where most common to see CD in GI tract?

A

terminal ileum

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18
Q

CD Pathophysiology Complications

A

small bowel stricture and obstruction possible

fistula common (20 - 40% lifetime risk)

less bleeding than UC (anemia is possible)

Risk of carcinoma is increased (not as high a risk as UC)

nutritional deficiencies: wt loss, growth failure in children deficiencies (iron deficiency anemia, vitamin B12, folate), hypoalbuminemia, hypokalemia, osteomalacia

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19
Q

Extraintestinal Manifestations of IBD: Bone and Joint

A

arthritis –> asymmetrical, migratory, typically involves one/few large joints

may be at increased risk for metabolic bone disease and osteoporosis (nutritional deficiencies: Ca and vitamin D, inflammation, hypogonadism, use of corticosteroids)

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20
Q

Extraintestinal Manifestations of IBD: Hematologic

A

anemia (prevalence up to 74%): iron deficiency, anemia of chronic disease, blood loss

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21
Q

Extraintestinal Manifestations of IBD: Coagulation***

A

1.5 - 3.6x increase risk of VTE

higher during flares, consider prophylaxis if admitted for flare

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22
Q

Extraintestinal Manifestations of IBD: Dermatologic and Mucocutaneous

A

variety of skin and mucosal lesions

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23
Q

Clinical Presentation of UC

A

highly variable

abdominal cramping

frequent BMs +/- blood +/- mucous

wt loss

paradoxical constipation possible

fever/tachycardia

extraintestinal: blurred vision/ocular signs

hemorrhoids, anal fissures

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24
Q

UC Laboratory Tests

A

decreased Hb/HCT

Increased ESR/CRP

leukocytosis, hypoalbuminemia (severe dz)

***fecal calprotectin (FC) and fecal lactoferrin (FC correlates with degree of inflammation, more sensitive and specific than serum markers)

diagnosis made on clinical suspicion and confirmed by endoscopy and biopsy

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25
Q

UC: disease extent determined by ____________

A

endoscopy

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26
Q

4 ways to classify a UC patient

A

remission

mild (< 4 stools, intermittent blood, normal hemoglobin)

moderate-severe (> 6 stools, frequent blood in stools, Hgb < 75% normal)

fulminant (> 10 stools, continuous bloody stool, required transfusion)

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27
Q

Clinical Presentation of CD

A

highly variable, characterized by periods of remission and exacerbation

typically diarrhea and abdominal pain (hematochezia in ~50% of patients)

Dx involves clinical evaluation in addition to endoscopic (upper and lower), laboratory, radiologic testing

malaise, fever, abdominal pain, frequent BMs, wt loss

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28
Q

CD Laboratory Tests

A

Hb/HCT

increased WBCs, ESR, CRP

fecal calprotectin and fecal lactoferrin

(+) anti-saccharomyces cervisiae antibodies (routine use not recommended)

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29
Q

CD Disease Classification

A

no global classification

CDAI (Crohn’s disease activity index): Used most frequently in research to gauge response to therapy and determine remission

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30
Q

How to classify CD***

A

Mild-moderate: ambulatory with minimal other Sx (dehydration, systemic toxicity), CDAI 150 - 220

Moderate-severe: patients who fail therapy for mild-moderate disease or those with fever, wt loss, abdominal pain/tenderness, vomiting, obstruction, anemia (here is where you really start to see Sx), CDAI 220 - 450

Severe-fulminant: persistent Sx or evidence of systemic toxicity despite corticosteroid or biologic tx or presence of cachexia (wasting disease), CDAI > 450

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31
Q

IBD Tx Overview

A

highly individualize. May include:

  • resolve acute inflammation/tx of disease flare
  • resolve and/or prevent complications
  • maintain remission
  • alleviate extraintestinal manifestations
  • avoid need for surgical palliation/cure

Want to get patients off of steroids~!

Inducing remission is an important aspect of therapy

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32
Q

IBD nutrition support

A

no specific diet shown to be beneficial

address nutritional deficiencies (avoid parenteral nutrition unless absolutely necessary)

some benefit with probiotic therapy

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33
Q

Nonpharmacologic therapy: Surgery

A

resecting areas of inflammation

colectomy rates in UC ~ 5 - 30% (may be necessary if failed pharmacologic therapy)

surgery indications for CD are less established

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34
Q

Certolizumab pegol (Cimzia)

A

only for CD

SQ injection

for mod-severe active CD

we do see the development of antibodies against these drugs

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35
Q

Natalizumab (Tysabri)

A

anti-alpha-subunit of integrin’s (prevents leukocyte adhesion/migration)

CD: induces and maintains remission

NOT used in combo w/ immunosuppressants

ONLY for CD

used in pts who fail TNF-alpha inhibitors

d/c in pts w/ no benefits by 12 weeks –> associated w/ progressive leukoencephalopathy (PML) –> the activation of a latent virus –> can be rapidly debilitating or fatal. can test pts for JC antibodies

drug is non specific

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36
Q

Vedolizumab (entyvio)

A

related to natalizumab

inhibits alpha 4 beta 7 subunit which is gut specific

targets lymphocytes active in the gut –> safer than natalizumab

for UC and CD

same ADRs as other biologics

NOT associated w/ PML (still monitor neurological changes)

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37
Q

Ustekinumab (stelara)

A

for both UC and CD

IL-12 and IL-23 specific

dosed IV (wt based induction) and subQ

ADRs similar as other biologics

unique ADR: rapidly developing skin cancer, possible neurotoxicity (PRES, typically stops once d/c drug)

TDM (therapeutic drug monitoring is possible)

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38
Q

For biologics…

A

…monitor tx response after start to see lack of response. Check [ ]

39
Q

ADA

A

anti-drug antibodies

40
Q

Tofacitinib (Xeljanz) - NOT A BIOLOGIC

A

Newer small molecule drug

oral Janus kinase (JK) inhibitor

UC only (for pts who had inadequate response/can’t tolerate other therapies like TNF inhibitor)

serious ADR, poorly tolerated, can be associated w/ neutropenia. Black box warning (2): increase mortality in RA pts 50 years and older w/ at least one CV risk factor AND thrombosis (PE, DVT, Arterial) in RA pts 50 years and older w/ at least one CV risk factor

rapid onset

do not use with other immunosuppressants or biologics

if pt has renal impairment, maybe avoid this drug

don’t use with strong CYP3A4 inhibitor, but if you do, decrease dose by 50%

41
Q

Ozanimod (Zeposia)

A

just approved in May of 2021!

oral selective sphingosine-1-phosphate (S1P) receptor modulator. prevents lymphocyte mobilization to inflammatory sites

moderate-severe UC only

7 day dose titration

contraindicated in pts who had previous CV events, pts w/ sleep apnea, in pt’s taking MAO inhibitor

21 hour half life

metabolized by ALDH/____ —> dont use in pts with hepatic impairment

theoretical PML risk

make sure pt is vaccinated

we see increases in ALT 5 fold upper limit of normal. If LFTs have a > 5 fold increase, d/c drug

associated with Hypertensive crisis

has an active metabolite, avoid using with MAO inhibitors

co-administration with CYP2C8 inducers + inhibitors –> can increase active metabolite –> coadministration not recommended

42
Q

antimicrobials role

A

if pt has CD and they have fistulas and abscesses, use anti-microbials as adjunctive tx

worry about Clostridium difficile because it mimics other Sxs

43
Q

sulfasalazine (ASA Agent)

A

sulfapyridine (a sulfonamide) + 5-ASA (mesalamine)

sulfapyridine is inactive but associated with ADRs

5-ASA is the active component (MOA = include anti-inflammatory effects, free radical scavenging)

44
Q

Mesalamine (ASA Agent)

A

CAN administer mesalamine alone

rapidly and completely absorbed in small intestine BUT NOT COLON

generally topical is more effective than oral

can use oral and topical together

45
Q

Topical (enema) mesalamine for

A

left-sided disease

46
Q

Suppository mesalamine for

A

proctitis (inflammation of the rectum lining)

47
Q

Oral mesalamine for

A

delayed/controlled release

examples

  • Apriso releases in colon and dissolves at >/= pH 6
  • Lialda releases evenly throughout colon (terminal ileum) at pH >/= 6.8
  • Pentasa releases in duodenum and ileum, up to 60% of dose reaches colon
  • Asacol HD and Delzicol dissolves at >/= pH 7. releases in terminal ileum
  • olsalazine (dipentum) released after colonic bacteria cleaves bond, release in colon
  • Balsalazide (colazal) released after colonic bacteria cleaves bond, releases in colon
48
Q

Apriso releases in

A

colon

49
Q

Lialda releases in

A

terminal ileum

50
Q

Pentasa releases in

A

duodenum, ileum

51
Q

Asacol HD, Delzicol releases in

A

terminal ileum

52
Q

Osalazine releases in

A

colon

53
Q

Balsalazide releases in

A

colon

54
Q

sulfasalazine is associated with

A

ADRs (really NO reason to continue using this)

> 10%: N/V, HA, anorexia, rash

<10%: anemia, hepatotoxicity, thrombocytopenia

hypersensitivity rxns in sulfonamide allergy

always titrate slowly

55
Q

sulfasalazine monitoring parameters

A

CBC, LFTs, BUN/Scr

56
Q

sulfasalazine drug interactions

A

antiplatelet/anticoagulants/NSAIDs –> may increase bleeding risk (ASA)

57
Q

mesalamine _____________ than sulfasalazine

A

much better tolerated

common SEs: N/V, HA

up to 80% of pts intolerant to sulfasalazine will tolerate mesalamine

58
Q

mesalamine drug interactions

A

antiplatelet/anticoagulants/NSAIDs –> may increase bleeding risk (ASA)

agents affecting gastric pH (PPIs, H2RAs, antacids) –> could influence release of drug in pH dependent dosage forms

59
Q

Corticosteroids used for ____________ but not for _____________

A

remission; maintenance

corticosteroids = anti-inflammatory

can be parenteral, oral or rectally

rectal hydrocortisone:

  • suppositories, foam, enema
  • note that systemic absorption is possible with rectal formulations
60
Q

Budesonide General Information

A

administered PO in CR formulation

first pass metabolism –> minimal systemic exposure

6 - 8 g

8 weeks (16 weeks)

Enterocort (brand) dosage form dissolves at PH > 5.5

Uceris (brand) dissolves at pH >/= 7. both PO and a foam

61
Q

Budesonide drug interactions

A

CYP3A4 inhibitors –> may increase systemic exposure

ADRs: similar to other glucocorticoids but it is generally well-tolerated

62
Q

Systemic Corticosteroids

A

must taper

parental typically for in-patients

*may be used for disease flares/induction of remission

give Ca and vitamin D while on steroids. may consider bisphosphonates in pts w/ osteoporosis

monitoring: occasional bone mineral density scan (DEXA) in pts > 60

63
Q

Oral Corticosteroids

A

Prednisone, Prednisolone

64
Q

IV Corticosteroids

A

Methylprednisolone, hydrocortisone

65
Q

Azathioprine (AZA) and Mercaptopurine (MP, 6-MP) facts

A

can be effective in long term tx of UC and CD

Do not induce but can MAINTAIN remission

generally reserved for pts who fail 5-ASA and/or patients who are refractory to/dependent on steroids

b4 initiating, check genetics, check TPMT

66
Q

Azathioprine (AZA) and Mercaptopurine (MP, 6-MP) not recommended for…

A

…MONOTHERAPY

67
Q

AZA is a…

A

pro-drug that is rapidly converted to 6-MP

68
Q

AZA and 6-MP ADRs

A

GI: N/V/D, anorexia, stomatitis

hematologic: BONE MARROW SUPPRESSION
hepatic: hepatotoxicity
idiosyncratic: fever, rash, arthralgia, pancreatitis

69
Q

AZA and 6-MP monitoring

A

TPMT (anything other than wild type = adverse effects)

CBC

LFTs

70
Q

Cyclosporine facts

A

common in transplant patients

effective inducing remission in pts w/ refractory IBD

NOT recommended for CD

Not for long term use

NOT COMMON for IBD

71
Q

Cyclosporine ADRs

A

nephrotoxicity (dose related)

neurotoxicity

metabolic (HTN, hyperlipidemia, hyperglycemia)

other: GI upset, gingival hyperplasia, hirsutism

72
Q

Cyclosporine monitoring

A

BP

BUN/Scr

LFTs

Cya tr. conc

73
Q

Cyclosporine drug interactions

A

substrate for CYP3A4 and P-glycoprotein

drugs/foods that increase cyclosporine concentrations: azole anti-fungals, macrolide antibiotics, ca channel blockers, grapefruit and grapefruit juice

drugs that decrease cyclosporine concentrations: phenytoin, rifampin

74
Q

Tacrolimus and IBD…

A

used in refractory disease although role is less defined

75
Q

Methotrexate (MTX) facts

A

can be used in CD. may have steroid sparing effects

76
Q

MTX ADRs

A

hematologic: bone marrow suppression (add folic acid 1 mg/day)

GI: N/V/D, stomatitis, mucositis (1mg folic acid)

hepatic: cirrhosis, hepatitis, fibrosis
pulm: hypersensitivity pneumonitis
derm: rash, urticaria (hives), alopecia

ALSO MTX IS TERATOGENIC

77
Q

MTX contraindications

A

pregnancy

pleural effusions

chronic liver disease/EtOH abuse

immunodeficiency

preexisting blood dyscrasias

leukopenia/t. cytopenia

CrCl < 40 ml/min

78
Q

MTX monitoring

A

CXR, CBC, Scr, LFTs

79
Q

infliximab (Remicade)

A

anti-TNF alpha antibody

CD and UC

80
Q

adalimumab (Humira)

A

anti-TNF alpha antibody

CD and UC

81
Q

golimumab (Simponi)

A

human monoclonal anti-TNF-alpha antibody

UC

82
Q

certolizumab pegol (Cimzia)

A

human pegylaged anti-TNF alpha Fab fragment

CD

83
Q

natalizumab (Tysabri)

A

anti-alpha-subunit of integrin’s (prevents leukocyte adhesion/migration)

CD

84
Q

vedolizumab (Entyvio)

A

anti-alpha-4-beta-7 integrin antibody (alpha-4-beta-7 integrin is expressed on subset of T-lymphocytes)

UC and CD

85
Q

ustekinumab (Stelara)

A

IL-12 and IL-23 antagonist

CD and UC

86
Q

Name the two small molecule drugs

A

ozanimod (Zeposia)

tofacitinib (Xeljanz)

87
Q

ozanimod (Zeposia)

A

oral sphingosine-1-phosphate (S1P) receptor modulator

UC

88
Q

tofacitinib (Xeljanz)

A

oral Janus kinase inhibitor (JK) inhibitor

UC

89
Q

Do NOT initiate TNF-alpha inhibitors during…

A

…active infections

90
Q

TNF-alpha inhibitor ADRs

A

increase risk of serious infections (bacterial, viral, fungal)

live vaccines contraindicated during tx and for 3 mo after

risk of malignancy

hepatosplenic T-cell lymphoma (HSTCL) risk

risk of demyelinating disease

may exacerbate CHF

91
Q

Monitoring for TNF-alpha inhibitors

A

CXR, PPD, S/S infection, UA, CBC, Scr, lytes, LFTs, Hep B, Hep C

92
Q

Infliximab (Remicade)

A

UC and CD (both moderate to severe)

development of antibodies to infliximab –> decreased tx response

combining with immunosuppressives may be of value

hepatosplenic T-cell lymphoma (HSTCL) risk

infusion related reactions

93
Q

Adalimumab (Humira)

A

UC and CD (both moderate to severe)

*can use for pts with poor response to infliximab

can lead to the development of ADAs (human-derived, potentially less likely than infliximab)

94
Q

Golimumab (Simponi)

A

UC (moderate to severe)

can lead to the development of ADAs (human-derived, potentially less likely than infliximab)

TDM possible: > 2.5 - 3.8 mcg/ml (week 6) and > 1.4 - 2.4 mcg/ml (maintenance)

Therapeutics IV (19 decks)

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