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PHRM 864 > IBD > Flashcards

IBD Flashcards

1
Q

what is crohn’s disease?

A

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

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2
Q

what is Ulcerative Colitis?

A

Mucosal inflammation confined to the rectum and colon

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3
Q

cytokine dysregulation in CD

A

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

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4
Q

cytokine dysregulation in UC

A

increased Th2 cytokine activity (IL-12, IL-5)

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5
Q

CD diet association

A

refined sugars, low in fruits and veggies, high in w-6 polyunsaturated fats

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6
Q

UC diet association

A

high protein

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7
Q

how does smoking affect UC and CD?

A

UC– protective? reduced disease activity with fewer flare-ups
CD– increased frequency and severity

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8
Q

NSAIDS IBD recommendation

A

generally avoid

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9
Q

Drugs that may cause IBD

A

NSAIDS, antibiotics

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10
Q

UC pathophys

A
  • confined to rectum and colon in the mucosal and submucosal layers
  • ulceration and mucosal damage = diarrhea and bleeding
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11
Q

UC local complications

A

hemorrhoids, anal fissures, perirectal abscesses

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12
Q

toxic megacolon

A

severe and potentially fatal UC complication; segmental or total colonic distention with acute colitis and signs of systemic toxicity
includes:
- increased ulceration depth
- vasculitis and thrombosis
- colonic dilation and/or perforation
- fever, tachycardia, distention, elevated WBCs

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13
Q

Other UC complications

A

colonic perforation
massive colonic hemorrhage
colonic stricture

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14
Q

colorectal cancer in UC

A

increased risk.
recommend screening colonoscopy with biopsies at 8 years after UC onset, and 1-2 years after that.

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15
Q

crohn’s disease pathophys

A
  • transmural inflammation
  • anywhere in GI tract
  • discontinuous
  • deep ulcers
  • luminal narrowing
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16
Q

crohn’s complications

A
  • small bowel stricture and obstruction
  • fistula (pathogenic connection between bowel and other tissue)
  • less bleeding than UC
  • some increased carcinoma risk
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17
Q

nutritional deficiency in CD

A
  • weight loss
  • growth failure
  • iron deficiency
  • vitamin B12
  • folate
  • hypoalbuminemia
  • hypokalemia
  • osteomalacia
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18
Q

extraintestinal IBD manifestaions

A
  • fatty liver, pericholangitis, autoimmune hepatitis, cirrhosis
  • primary sclerosing cholangitis, cholangiocarcinoma, cholelithiasis
  • iritis, episcleritis, conjunctivitis
  • arthritis
  • osteoporosis (nutrient deficiency)
  • anemia
  • coagulation (VTE risk)
  • skin and mucosal lesions
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19
Q

clinical presentation of UC

A
  • abdominal cramping
  • frequent BMs and blood and mucous in stool.
  • weight loss
  • constipation
  • fever/tachycardia
  • blurred vision, arthritis, dermatologic
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20
Q

physical exam findings of UC

A
  • hemorrhoids, anal fissures, abscesses
  • dermatologic/ocular
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21
Q

labs results of UC

A
  • decreased Hb/HCT
    Increased ESR/CRP
  • leukocytosis, hypoalbuminemia
  • fecal calprotectin (FC) (FC correlates with degree of inflammation)
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22
Q

diagnosis of UC

A

confirmed by endoscopy and biopsy
negative stool exam for infectious causes.

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23
Q

signs and symptoms CD

A

malaise, fever, abd pain, frequent BMs, hematochezia, fistula, weight loss, arthritis
abdominal mass/tenderness, perianal fissure, fistula

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24
Q

Lab tests CD

A

Hb/HCT
Increased WBCs, ESR, CRP
Fecal calprotectin and fecal lactoferrin
+ anti-saccharomyces cervisiae antibodies

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25
Clinical presentation CD
variable typically presents with diarrhea and abdominal pain hematochezia in ~50% endoscopy required for diagnosis
26
CD disease classification
mild-moderate: ambulatory; minimal other symptoms; no obstruction CDAI 150-220 moderate-severe: failed therapy for mild-moderate disease. Fever, weight loss, abd pain and tenderness, vomiting, obstruction, anemia. CDAI 220-450 severe-fulminant: persistent symptoms; systemic toxicity; CDAI >450
27
ASA Agents
sulfasalazine and 5-ASA (mesalamine)
28
Sulfasalazine MOA
cleaved by colonic bacteria to release sulfapyridine (inactive) and 5-ASA (active)
29
MOA 5-ASA
local actions anti-inflammatory free radical scavenging
30
Mesalamine dosage forms
- rapidly and completely absorbed in the small intestine (not the colon) - enemas (for left-sided disease) - suppositories (proctitis) - delayed/controlled release oral - can use topical and oral together
31
Oral mesalamine
Apriso: releases in colon 0.375g mesalamine Lialda: 1.2g mesalamine. released evenly throughout colon. pentasa: 250 or 500mg. released in duodenum or ileum. dosed QID. Asacol HD and Delzicol: 800mg (HD) or 400mg (delzicol) released in terminal ileum. TID dosing Olsalazine (dipentum): 250mg dimer. released by bacteria in colon. BID dosing Balsalazide (Colazal): Prodrug released by bacteria in colon. (750mg TID)
32
Sulfasalazine ADRs
ADRs due to sulfapyridine - nausea, vomiting, HA, anorexia, rash (start low-dose) - anemia, hepatotoxicity, thrombocytopenia - pneumonitis, lymphoma, nephritis - hypersensitivity due to sulfonamide Monitoring: CBCs and LFTs at baseline, every other week for first 3 months, and monthly for second 3 months, and periodically, thereafter. Monitor BUN/Scr periodically. - interacts with anticoagulants/NSAIDS to increase bleeding risk.
33
Mesalamine ADRs
- better tolerated than sulfasalazine - nausea, vomiting, HA - olsalazine: diarrhea - diarrhea, rash/pruritis, constipation - anemia, hepatitis/ abnormal LFTs, UC exacerbation - drug interactions: NsAIDS/antiplatelets/anticoagulants: Bleeding risk - PPIs, H2RAs, antacids (could influence release of dug in pH dependent dosage forms)
34
Corticosteroids MOA
- anti-inflammatory (parental for severe exacerbation, oral, or rectal) - use for remission induction only rectal dosing: 100-200mg per day (may be absorbed systemically)
35
Budesonide
- PO in CR formulation - first-pass metabolism (only 9-21% absorbed systemically) - 6-8mg/day for up to 8 weeks - Enterocort EC (ileum) and Uceris (colon)
36
Budesonide drug interactions
CYP3A inhibitors (ketoconazole, grapefruit, etc.) May increase systemic exposure.
37
Systemic Corticosteroids
Prednisone or prednisolone 40-60mg/day - TAPER - IV methylprednisolone (16-20mg q6h) - IV hydrocortisone (100mg q8h) - remission induction only
38
Steroids ADRs
- give calcium and vitamin D while on steroids - may consider bisphosphonate - bone mineral density scan occasionally
39
Azathioprine and 6-MP uses
- can be used long-term for both UC and CD - for patients who fail 5-ASA and dependent on steroids - can help maintain remission (steroid sparing) - can use with 5-ASAs, steroids, and TNF-A - need to use for weeks to months to see benefit
40
AZA and 6-MP dosing
AZA: 0.5-1.5 mg/kg IBW. Max of 2.5 mg/kg/day 6-MP: 0.25-0.5 mg/kg IBW. Max of 1-1.5 mg/kg/day
41
AZA and 6-MP ADRs
- N/V/D, anorexia, stomatitis - bone marrow suppression hepatotoxicity - fever, rash, arthralgia, pancreatitis monitoring: TPMT, CBC, LFTs
42
Cyclosporine
- can induce remission in IBD (UC) - Not in CD - Not for long-term use - for patients dependent on steroids initial IV 2-4 mg/kg/day PO conversion: double IV dose and administered 1/2 Q12H, then taper
43
Cyclosporine ADRs
- nephrotoxicity - neurotoxicity - metabolic (HTN, HLD, hyperglycemia) - GI upset, gingival hyperplasia, hirsutism
44
Cyclosporine monitoring
- BP, BUN/Scr, LFTs, trough concentration
45
Cyclosporine Drug interactions
- CYP3A and PGP substrate - conc increased due to: azole anti-fungals, macrolide abx, CCBs, grapefruit - conc dec due to: phenytoin, rifampin
46
Tacrolimus
can be used in refractory disease
47
Methotrexate uses
- Used in Crohns - steroid sparing, induces remission - less defined role in UC (combo therapy) - SubQ or IM
48
Methotrexate ADRs
- bone marrow suppression - N/V/D, stomatitis, mucositis - cirrhosis, hepatitis, fibrosis - hypersensitivity pneumonitis - rash, urticaria, alopecia - teratogenic
49
Methotrexate contraindications
- pregnancy - pleural effusions - Chronic liver disease (EtOH use) - immunodeficiency - leukopenia/cytopenia - CrCl <40 - blood dyscrasia
50
methotrexate monitoring
CXR, CBC, SCr, LFTs
51
TNF-a antagonists
infliximab (CD and UC) adalimumab (CD and UC) golimumab (UC) (go from the colon) certolizumab pegol (CD) (larissa is a certified a-hole)
52
Natalizumab (tysabri)
- prevents leukocyte adhesion/migration - Crohn's only - Natal (friends with natalia?)
53
Vedolizumab
anti-a4b7 integrin antibody - Both UC and CD
54
IL antagonists
- ustekinumab (stelara) (IL-12 and IL-23) (CD and UC) - risankizumab-rzaa (Skyrizi) (IL-23) (CD and UC) - mirikizumab-mrkz (Omvoh) (Il-23 and P19) (UC only)
55
Small molecule drugs
- tofacitinib (Xeljanz) (Oral JAK inhibitor) (UC only) - upadacitinib (Rinvoq) (Oral JAK1 inhibitor) (UC and CD) - Ozanimod (Zeposia) (Oral S1P receptor modulator) (UC only) - estrasimod (Velsipity) (Oral S1P) (UC only)
56
infliximab
UC and CD - induction and maintenance - Anti-drug antibody risk - can combine with immunosuppressives IV infusion
57
adlimumab
_- UC and CD - induction and maintenance - ADA risk - SQ injection
58
Golimumab
- UC only - induction and maintenance - ADA risk - SQ injection
59
certolizumab
- CD only - induction and maintenance - SQ injection - ADA risk
60
natalizumab
- CD only - induction and maintenance - cannot use with immunosuppressants IV
61
Vedolizumab
- UC and CD - induction and maintenance - IV
62
ustekinumab (stelara)
- UC and CD - IV (induction), SQ (maintenance)
63
risankizumab-rzaa (skyrizi)
- CD and UC - IV and SQ - induction and maintenance (moderate to severe) - avoid live vaccines
64
Mirikizumab-mrkz (omvoh)
- UC only - induction and maintenance - IV and SQ - avoid live vaccines
65
when should TDM be used?
- most data for infliximab and adalimumab - also check ADA
66
TDM
- therapeutic drug levels no effect (always switch to out of class biologic) - subtherapeutic levels (detectable ADA's change to alternate drug in same class) (undetectable ADAs escalate dose)
67
Tofacitinib (Xeljanz)
- Oral JAK inhibitor - UC only - intolerant to TNF blockers - do not use with immunosuppressants - CYD interactions - thrombosis risk - avoid live vaccines
68
Upadacitinib (Rinvoq)
- Oral JAK-1 inhibitor - UC and CD - intolerant to TNF blockers - do not use with immunosuppressants or other biologics - CYP interactions - live vaccines contraindicated - shingles risk
69
Ozanimod (Zeposia)
- S1P receptor modulatory - UC only - do not use with immunosuppressants - Cardiac contraindications - Bradycardia and AV conduction delays - Interactions with CYPs, MAO-Is, BB, CCBs, etc.
70
estrasimod (Velsipity)
- s1P receptor modulator - UC only - no immunosuppressants - c/i with caridac conditions - CYP interactions - JC virus
71
antimicrobians
- ciprofloxacin, metronidazole, rifamycin (may cause resistance and C.diff)
72
Mild to moderate UC treatment
- oral and topical ASAs - Oral if disease extensive - mesalamine enemas and suppositories - mesalamine better tolerated than sulfa - can use oral and topical together!!
73
unresponsive to 5-ASA in Mild-to-moderate active UC
use high-dose mesalamine and rectal mesalamine
74
mild to moderate
- can use budesonide and prednisone - when non-reponsive to oral or topical 5-ASAs - typically limit use to short-term
75
moderate to severe active UC
- 4-6 stools/day, blood, and some systemic symptoms - 5-ASA for moderate (not severe) - use systemic steroids (prednisone or budesonide) - consider TNF-a or other biologics when 5-ASA fails and steroid-dependent
76
moderate to severe active UC
TNF-a inhibitors: infliximab, adalimumab, golimumab antiintegrin: vedolizumab IL12/IL-23: ustekinumab, mirikzumab, risankizuab JAK: upadacitinib, tofacitinib (only if fails TNF-a) Black box warnings SP1 inhibitor: Ozanimod and etrasimod
77
moderate to severe active UC
do not use methotrexate for induction or maintenance; use biologic monotherapy - use steroids for induction - may use thiopurine monotherapy for maintenance - Combine TNF-a with thiopurines or MTX - discontinue 5-ASA for maintenance
78
Severe UC
- requires inpatient tx - 6-10 BMs/day - NPO - Parenteral steroids (methylpred, hydrocortisone) - TNF-a (infliximab and cyclosporine) -cyclosporine and transition to thiopurines (aza or 6-MP)
79
maintenance of remission
- Use ASA (mesalamine) (oral and/or enema) or TNF-a - azathioprine or 6-MP (Combine with TNF-a to decrease antibodies) - do not continue steroids
80
mild to moderate crohns
no longer recommend mesalamine derivatives - use budesonide - antibiotics - may use sulfasalazine for mild disease
81
moderate to severe crohns
- steroids - biologic therapy - TNF-a (infliximab + AZA or MTX) - adalimumab + thiopurine (AZA) - Certolizumab (not first line)
82
Do NOT USE in Crohns
- 5-ASA or sulfa - Cyclosporine
83
fulminant crohns
steroids, infliximab last line, then surgery
84
CD maintenance of remission
AZA and 6-MP or SQ MTX - TNF-a (use with AZA or 6-MP) - early initiation of biologic in moderate-to-severe disease
85

PHRM 864 (13 decks)

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