Lecture 10 - Irritable Bowel Disease Flashcards

1
Q

Left sided UC or CD refer to….

A
  1. Transverse colon

2. Proctitis

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2
Q

Right Sided UC or CD refers to….

A
  1. Terminal ileum

2. Ascending colon

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3
Q

fistulas and abscesses are likely to occur in CD due to the transmural nature of the disease….

A

True

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4
Q

Txm Goals of IBD

A
  1. relief symptoms
  2. improve quality of life
  3. maintaining adequate nutrition
  4. control/minimizing complications
  5. achieve + maintain remission
  6. achieve mucosal healing
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5
Q

Induction therapy

A

therapy to target acute disease flare

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6
Q

Maintenance remission

A

acute disease flare adequately managed
therapy to minimize further acute flares
defined as CDAI < 150 in studies

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7
Q

Treatment refractory

A

failed response to standard therapy

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8
Q

Steroid dependence vs resistance

A

steroids not a good long term solution*** never choose that option

intended for short period and then taper

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9
Q

non-pharm treatment options for IBD

A

Diet
Probiotics
Surgery = most common performed in UC pts, more benefit due to localized disease

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10
Q

Sulfasalazine Common Adverse effects

A

15% D/c use due to N/V, headache, Anorexia

Severe ADE: Hypersensitivity (sulfa), Hepatitis, Hemolytic anemias, Agranulocystosis, Pancreatitis

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11
Q

Sulfasalazine MOA:

A

composed of mesalamine + sulfapyridine.

sulfapyridine gets cleaved = sulfa allergy issues

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12
Q

Mesalamine SE

A

better than Sulfasalazine

GI: abdom pain, constipation
Hypersensitivity to mesalamine, aminosalicyates, salicylates
Nasopharyngitis

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13
Q

Mesalamine CI

A

GFR < 30ml/min

severe hepatic impairment

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14
Q

Mesalamine Typical response rate

A

2-4 weeks

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15
Q

Mesalamine/ASA formulation & Delivery

A

Mess sup - reach only around rector ~ 15cm

Mess enema - reach farther, distal colon

Branded mess - reach further up, oral time release Terminal ileum/Proximal colon

ASA HD -passed terminal ileum, almost ileum

Pentasa - all the way through to jejunum

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16
Q

Other Aminosalicylates + common SE

A

Olsalazine
Balsalazide

Common: osmotic diarrhea
Balsalazide: HA, abdominal pain

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17
Q

Corticosteroids SE + responso time

A

Shit load, which is why we dont use chronic

response in like 7-10 days

short term SE:

CNS: anxiety, insomnia, psychosis
Endo: Hyperglycemia
GI: weight gain, esophagitis, bleeding

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18
Q

Budesonide Common SE:

A

HA
Nausea
Acne
Respiratory infections

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19
Q

Other info Budesonide

A

Extensive 1st past metabolism, not approved for maintenance + long term management

Entocort EC = indicated for CD
Uceris MMX = indicated for UC

Less systemic absorption, potentially less SE

$$$

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20
Q

Immunosuppressives - Thiopurines

A

Aza (Azathioprine) & 6-MP (6-Mercaptopurine)
Aza converte to 6-MP by enzyme TPMT

caution in ppl who are not good metabolizers TPMT

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21
Q

AZA & 6-MP common SE

A

Anorexia
Nausea
Vomiting
Diarrhea

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22
Q

AZA & 6-MP Severe Adverse SE

A

Hematolig/Leukopenia = monitor WBC**

Hepatotoxicity = dose related, reversible

Pancreatitis
Hepatosplenic lymphoma

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23
Q

Drug interactions of AZA & 6-MP

A

Significant DI w/ Allopurinol, reduces 6-MP metabolism = inc lvls and toxicity

reconsider use or reduce AZA/6-MP dose by 25-30%

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24
Q

Onset of action AZA + 6-MP

A

2-3 months

> 4 months for optimal efficacy

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25
Q

Assessing TPMP phenotype prior to starting therapy….

A

pts who have low enzyme lvls increased risk of severe leukopenia

if no active TPMP activity, don’t initiate
if intermediate TPMP activity, reduce start dose 25-50%

26
Q

Methotrexate info

A
  1. Limited role in UC, primarily used in CD
  2. Long term SE, monitor WBC, RBC,PLT
    GI ulceration + bleed, hepatoxicity (ALT,ASLT, LFTs)
    Pulmonary fibrosis/pneumonitis
27
Q

Cyclosporine info

A

Primarily used in UC, typically not recommended for treatment of CD except for acute management of pts with severe fistulizng disease

used in hospital, have to monitor levels, bunch of DI CYP3A4

SE: HTN, edema, tremor, nephrotoxicity

28
Q

Cyclosporine trough conc + response

A

300-500 mg/ml for IV

average response seen in 8 days

29
Q

Immunosuppressives are usually used for….

A

maintenance remission therapy

due to long time to take to work

30
Q

Infliximab common ADE

A
HA
Abdominal pain
Infections, URI, sinusitis
Dyspnea
Urticaria

fairly well tolerated overall

31
Q

Inflixima info

A

black box warning for inc risk of developing infections

can reactivate latent TB

infusion reactions are possible, typically pts have fever, chills, and or pruritus

serum sickness with repeated doses are rare

32
Q

Adalimumab (Humira) SE

A

fully homogenized, better tolerated

Common: HA, rash, antibody development, inject site reactions, URI, sinusitis

Less common: HTN, confusion, N/V/ab pain, serious infection

33
Q

Golimumab Adverse side Effects

A

URI
Increased LFTs
Injection/dermatologic reactions

34
Q

Golimumab (Simponi) Severe Side effects

A
Infections:
Latent TB activation
Hep B react
Secondary malignancy
CHF exacerbations
MS (demylenating disease)
35
Q

Certolizumab (Cimzia) info

A

Pegylated human anti-tnf

similar efficacy to humira + infliximab

SE:
inc site reaction, cytopenias, Hep B reactivation, new or worsening HF

36
Q

Natalizumab (Tysabri) info

A

SE: rash, UTI, infection (flu), n, gastroenteritis, infusion related

Black box: increased risk of PML, often fatal

REMS restricted, access through TOUCH program

37
Q

Vedolizumab (entyvio)

A

MOA: works on T cells

Common SE: HA, arterialgia, nasopharyngitis

Less common SE: Fatigue, skin rash, infection, UTI, increased LFTs

38
Q

Ustekinumab (Stelara)

A

works on interleukins

SE: Serious infections, C.diff, UTI, some cases carcinoma

39
Q

Tofacitinib (Xeljanz)

A

MOA: inhibit JAK1/3, oral drug
Txm adults with mod/sever active UC

SE: influenza, nasopharyngitis, modest LDL/HDL inc

Rare: serious infections

** FDA safety warning inc risk of VTE pts taking standard 10mg BID dose **

40
Q

Upadacitinib (Rinvoq)

A

MOA: JAK1/3 inhib, also works on interleukin

SE ( >5%): URI, CK + LFT elevation, Acne, Neutropenia, Rash

41
Q

Ozanimod (Zeposia)

A

MOA: block lymphocyte egress from lymph node, reduce inflammation response

Common SE: URI, LFT elevation, HA

Serious SE: Infections (viral/fungal), Bradyarrhythmias + condition delays, HTN< Respiratory decline, Macular edema

42
Q

Biosimilars info

A
  1. similar amino acid sequences, but glycosylation differences between production can impact stability and immunogenicity

Must have same strength, dose form, route of admin and indication

43
Q

Antibiotic usage

A

not used for much, very specific indications for a few such as Metronidazole and Ciprofloxacin

44
Q

Mildly Active-Distal Ulcerative Colitis

A

Rectal (support + enema) mesalamine more effective than oral 5-ASA or topical steroids for distal disease

Combo oral + topical 5-ASAs more effective than either alone

Mesalamine prep typically better tolerated than sulfasalazine, usually 1st line***

45
Q

Mildly Active-Distal Refractory UC

A
  1. Corticosteroids (PO or IV), Burst therapy, taper over 6-8wks…2-4wk if tolerated
  2. Budesonide MMX, alternative or addition to 5-ASA intolerant/non-responders

PO+rectal combo better than solo

AZA + 6-MP = limited role, poor risk/benefit, not recommended

46
Q

Maintenance Remission w/ previously Mildly active Distal UC

A
  1. lower oral doses of agents (1g/day of 5-ASA)
  2. Oral+ topical formulations better than either alone
  3. Corticosteroids and budesonide not indicated
  4. Infliximab, AZA, 6-MP limited role, only in refractory pts
47
Q

Mildy Active Extensive UC info

A
  1. Oral 5-ASA (2g/day) 1st line, recommend against alternative 5-ASA for pts who fail to achieve remission on initial 5-ASA, higher doses not associated with better remission
  2. oral steroids typically used pts dont respond to combo oral+rectal 5-ASAs
  3. Infliximab effective pts steroid refractory or dependent
48
Q

Mildy Active Extensive UC 1st-3rd line

A
1st = oral Sulfasalazine or other 5-ASA 2-2.4g/day
2nd = Oral corticosteroids or budesonide as an alternative
3rd = Infliximab
49
Q

Maintenance Remission pts w/ previously Mildy active Extensive UC

A
  1. Lower dose 5-ASA ( sulfasalazine, olsalazine, mesalamine, balsalazide)
  2. AZA or 6-MP maybe used
  3. TNFi (infliximab pref)

** chronic oral corticosteroids not indicated **

50
Q

Mod-Severe Active Extensive UC, pts not req hospitalization

A
  1. Corticosteroid adjust can be considered

2. early biologic therapy recommended, anti TNF

51
Q

Mod-Severe Active Extensive UC, pts not req hospitalization…Biologic Naive….

A
  1. infliximab

2. Vedolizumab

52
Q

Mod-Severe Active Extensive UC, pts not req hospitalization….refractory to biologic agent….

A

Ustekinumab and tofacitinib

53
Q

Mod-Severe Active Extensive UC, pts not req hospitalization combo therapy

A

Thiopurines or MTX + biologic is better than biologic monotherapy

54
Q

Severe UC req Hospitalization or Fulminant Extensive disease

A
  1. give steroid
    1a. no response = cyclosporine or infliximab - if remission continue therapy, if no remission Colectomy
    1b. if remission = change to prednisone, add AZA/6-MP/infliximab or adalimumab and attempt withdrawal of steroid, continue if remission achieved
55
Q

Mild-Moderate Active CD

A

Systemic corticosteroids = prednisone w/ taper effective inducing remission

Antibiotics - limited efficacy, insufficient data

Controversial 1st line = Sulfasalazine (when involves colon) + Mesalamine ( targeting ill disease, better tolerated)

56
Q

Viable 1st line for CD confined to ileum and/or right colon?

A

Controlled release budesonide (Entocort)

57
Q

Moderate-severe active CD

A

Taper oral corticosteroids

anti-TNF used, combo more effective than mono

Ustekinumab = treatment resistant pts

AZA, 6-MP, Max = not effective short term

Cyclosporine, mycophenolate, taco = controversial but generally not efficacious

58
Q

Severe/fulminant Active Disease CD

A
  1. rule out obstruction, mass, abscess
  2. IV corticosteroids 1st line
  3. Limited data supporting anti-TNFs
59
Q

Perianal + Fistulizing disease

A

Anti-TNFs
AZA, 6-MP
Antibiotics

60
Q

Maintenance therapy for CD

A

long term corticosteroids not recommended

AZA, 6-MP preferred over MTX

5-ASA not effective/recommended