Therapeutics III > IBD > Flashcards

IBD Flashcards

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1
Q

IBD tx overview

A

-rx (induction and maintenance)
-surgery
-nutrition
-tx complications
-avoid exacerbating drugs

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2
Q

IBD goal of therapy

A

-induce and maintain remission
=improve outcomes and QOL
=dec complications
-mucosal healing may = better long-term outcomes
-consider corticosteroid free remission

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3
Q

Surgery for IBD

A

-resecting areas of inflammation
-colectomy if failed rx or severe complications
-protocolectomy often curative but = permanent ileostomy pouch
-restorative protocolectomy = try to reconnect small intestine to anus = no pouch but more infectious complications

-indications less established in CD, not v curative

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4
Q

Pharmacologic tx of IBD

A

-no agents are curative
-ASAs
-corticosteroids
-immunomodulators/suppressants (chemo)
-biologics
-JAK inhibitor
-S1P inhibitors

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5
Q

ASA drugs

A

-sulfasalazine (prodrug)
-mesalamine

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6
Q

Sulfasalazine

A

-ASA agent for IBD
-sulfa + mesalamine (5-ASA)
-cleaved by colon bacteria to release sulfapyridine and 5-ASA
-sulfapyridine inactive but inc ADRs (sulfa allergy + renal excretion)
-5-ASA active component

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7
Q

Mesalamine (5-ASA)

A

-can admin w/o sulfa
-but absorbed in small intestine not colon
-topical more effective than oral but you can combo them

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8
Q

Mesalamine dosage forms

A

-topical (enemas): left-sided disease
-supppository: proctitis
-oral: delayed or controlled release
-topical better than oral but can combo

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9
Q

Mesalamine oral agents

A

-apriso (release in colon pH≥ 6)
-lialda (colon, pH ≥ 6.8)
-pentasa (releases in small intestine, 60% reaches colon, QID)
-asacol and delzicol (ileum pH≥ 7, TID)
-olsalazine (sulfa = cleaved by bacteria in colon)
-balsalazide (sulfa)

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10
Q

Sulfasalazine ADRs

A

-sulfapyridine = ADRs
-N/V, HA, anorexia, rash
=start low inc over 1-2 weeks
-anemia, hepatotoxicity, thrombocytopenia
-sulfa allergy

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11
Q

ASA monitoring

A

-CBC and LFTs at baseline
-q other week for 3 months
-monthly for second 3 months
-periodically after
-periodically BUN/SCr

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12
Q

sulfasalazine drug interactions

A

-antiplatelets
-anticoags
-NSAIDs
=inc bleeding risk

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13
Q

Mesalamine ADRs

A

-better than sulfasalazine
-N/V, HA
-diarrhea (more w olsalazine)
-rash, constipation
-anemia
-hepatitis/LFTs
-UC exacerbation

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14
Q

Mesalamine drug interactions

A

-antiplatelet
-anticoags
-NSAIDs
-agents effecting pH can affect pH dosage forms (PPIs, H2RAs, antacids)

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15
Q

Corticosteroid MOA + use

A

-anti-inflammatory
-parental (severe), oral, rectal forms
-tx to induce remission
-NOT maintenance
=avoid long term

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16
Q

Rectal hydrocortisone

A

-suppositories
-foam
-enema
-systemic absorption possible

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17
Q

Budesonide

A

-steroid
-PO in CR form
-extensive first-pass metabolism = minimal systemic exposure
-up to 8 weeks
-enterocort pH > 5.5 (ileum)
-Uceris pH ≥ 7 (colon) also available as foam

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18
Q

Budesonide drug interactions + ADRs

A

-CYP3A4 inhibitors may inc systemic exposure (ketoconazole + grapefruit juice)
-similar ADRs to steroids but well tolerated

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19
Q

Systemic corticosteroids

A

-oral prednisone or prednisolone
-IV methlyprednisone or hydrocortisone
-may use for flares/induce remission

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20
Q

Systemic corticosteroids ADRs

A

-short term:
-hyperglycemi
-gastritis
-mood changes
-inc BP

-long-term:
-necrosis
-cataracts
-obesity
-growth failure
-HPA suppression (hard to ressucitate)
-osteroporosis

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21
Q

Systemic corticosteroid considerations

A

-give Ca and Vit D
-consider bisphosphonate in pt at risk of osteoporosis, pt using >3months, recurrent users

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22
Q

Systemic corticosteroid monitoring

A

-occassional bone density snac (DEXA) in pt >60, risk of osteoporosis, >3 months, recurrent users

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23
Q

Azathioprine (AZA) and 6-MP

A

-can be effective long term UC and CD tx
-reserved for pt who fail 5-ASA or dependent on steroids
-maintain remission (limited role in induction)
-can combo w 5-ASA, steroids, TNF-a antagonists
-need to be used weeks-months to see benefits
-AZA prodrug turned to 6-MP

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24
Q

AZA and 6-MP ADRs

A

-N/V/D, anorexia, stomatitis
-bone marrow suppression (TMPT gene toxicity)
-hepatotoxicity
-fever, rash, arthralgia, pancreatitis

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25
AZA and 6-MP monitoring
-TMPT genetic testing -CBC and LFTs at baseline -then q week one month -q1-2 weeks after dose change -q1-3 months after
26
Cyclosporine
-some efficacy in inducing remission in refractory/steroid dependent pt -avoid in CD -not long-term, use as bridge-tx -less role now bc biologics -initial IV infusion then PO
27
Cyclosporine ADRs
-nephrotoxicity (dose) -neurotoxicity -metabolic (HTN, lipids, sugar) -GI upset -gingival hyperplasia -hirsutism
28
Cyclosporine monitoring
-BP q visit -cya tr concentration (TDM?) -BUN/SCr -LFTs -q weeks until stable, then periodically
29
Cyclosporine drug interactions
-CYP3A4 and PgP substrate -inc cyclosprorine: azole, CCBs, grapefruit -dec: phenytoin rifampin
30
Tacrolimus
-used in refractory disease -less defined role
31
Methotrexate
-use in CD (MAYBE UC as combo tx) -may have steroid-sparing effects -assist in inducing remission -allow steroid-tapering -SC/IM
32
Methotrexate (MTX) ADRs
-bone marrow suppresion =add folic acid! -N/V/D, stomatitis, mucositits -hepatic -hypersensitivty pneumonitis -rash, alopecia -teratogenic =add contraception
33
MTX contraindications
-pregancy -pleural effusions -chronic liver disease -alcoholism -immunodeficiency -blood dyscrasis -leukopenia/cytopenia -ClCr<40ml/min
34
MTX monitoring
-CXR -CBC -SCr -LFTs -baseline and q1-2 months (not CXR tho, just baseline)
35
TNF-antagonists
-infliximib (IV) -adalimumab -golimumab (UC only) -certolizumab (?) -all SQ
36
Anti-a-integrins
-natalizumab -vedolizumab
37
JAK inhibitor drugs
-tofactinib -upadacitinib
38
S1P receptor modulator drugs
-ozanimod -estrasimod
39
TNF-a antagonist use
-induction and maintenance -combo w immunospressives (AZA, MTX) may be of value -may also inc ADRs
40
TNF-a inhibitor ADRs
-inc risk of serious infections -tuberculin test (PPD), CXR, hepatitis B/C before tx -make sure pt is vaxed but avoid live vax during and 3 months after tx -injection and infusion reaxtions -risk of malignancy (lymphoma) -hepatosplenia T-cell lymphoma (HSTCL) -risk of demyelinating dx -may exacerbate CHF (c/o in NYHA III-IV) -rare hepatotoxicity
41
TNF-a inhibitor monitoring
-baseline and q8-12 weeks -CXR (baseline) -PPD (baseline) -s/sx infection -UA -CBC -SCr, lytes -LFTs (possibly inc freq early inflammatory markers) -Hep B,C
42
TNF-a inhibitor MOA
-develop mAbs to tx -dec tx response -inc chance of infection -can escalate dose, dec interval -TDM (drug and aBs) may be of value
43
Natalizumab MOA + use
-anti-a-subunit of integrin -prevents leukocyte migration -CD only -induce and maintain remission -use if pt fails TNF-a (do NOT combo these two or w immunosppressants) -d/c in pt w no benefit afer 12 weeks or are still steroid dependednt within 6 months IV
44
Natalizumab ADRs
-PML -can test for JC aB but no gaurantee -hypersensitivity rxn -ADAs
45
Progressive Multifocal leukoencephaly (PML)
-rare, lethal untx CNS disorder related to viral infection (JC virus) -can test for JC aBs but no guarantee -inc risk w longer duration of natalizumab tx >2 years -prior immunosuppressant use -monitor closely for neurological events
46
Vedolizumab
-anti-a4B7 integrin aB -UC and CD tx -induce and maintain remission -dec steroid dependence -IV (new option for SQ) -TDM possible =induction then mainenance
47
Vedolizumab ADRs
-similar to other biologics -hypersensitivity -ADAs -NO PML
48
IL-12/IL-23 inhibitor drugs
-ustekinumab (IL-12) -risankizumab -mirikizumab-mrkz -guseulkumab (or SQ induction) -all IL-23 -all UC and CD tx -IV induction, SQ maintenance
49
IL-12/IL-23 inhibitor ADRs
-similar to other biologics -hypersensitivity -ADAs -hepatotoxicity (may inc LFTs) -carcinoma and neurtoxicity (ustekinumab
50
Ustekinumab (IL-12 AND IL-23) ADRs
-cutaneous cell carcinoma (skin cancer) in pt w risk factors` -possible neurotoxicity
51
IL-12/IL-23 inhibitor monitoring
-CXR, PPD (baseline) -Hep B, C (baseline) -lipids 1-2 mo after start, periodically -LFTs at initiation, periodically -renal fx at start and periodically -monitor infection -monitor skin annually (ustekinumab) =esp in pt >60, prolonged immunosuppressant tx, hx of phototherapy
52
TDM of biologics
-potential for determinging concentrations of drugs and ADAs -consider if LOSS of tx response (reactive TDM) -check ADA concurrently -may help justify dose inc to insurers
53
TDM slide
-subtherapeutic (PK) drug levels or therapeutic (PD) drug leves -and detectable or undetectable ADAs -immune mediated PK failure -non-immune mediated PK dailure -false positive/mechanistic failure -mech failure
54
IBD pt at tx failure
-confirm inflammation, clinical assessment, biomarkers -exclude infection and noncompliance to tx -send for serum drug TLs and ADA levels
55
Immune mediated PK failure
-subtherapeutic drug levels (PK) -DETECTABLE ADAs -insufficient bioavailability bc induced immunogenicity w fuctional ADA = inc drug clearance -change to alt drug within same class +/- immunomodulator
56
Non-immune mediated PK failure
-subtherapeutic drug levels (PK) -UNdetectable ADAs -insufficient availability of drug not due to ADAs -dose escalate
57
False positive
-therapeutic drug levels (PD) -detectable ADAs -repeat TDM levels for mechanistic failure
58
Mechanistic (PD) failure
-therapeutic drug levels (PD) -detectable or undetectable ADAs -PD issues inhibition of inflammation not effective of inflammation driven by alternate pathway -switch to out of class biologic
59
A patient is receiving adalimumab 40 mg SQ every second wk for CD. He had previously been fairly well controlled (i.e., in remission) for the past 12 months, but recently has had several episodes of increased disease activity (flares). A trough concentration is measured, and the concentration is 2.5 ug/ml (desired concentration >/= 8-12 ug/ml), and high concentrations of anti-adalimumab antibodies are detected. What type of failure is this: a) pharmacodynamic (mechanistic) failure b) immune mediated pharmacokinetic failure c) non-immune pharmacokinetic failure
-subtherapeutic levels (PK) -high ADAs = immune-mediated PK failure
60
JAK1 inhibitor drugs
-tofactinib (UC only) -upadacitinib (UC and CD)
61
JAK inhibitor use
-pt that failed TNF blockers -do NOT combo w immunosuppressants or biologics -rapid onset/short t1/2
62
JAK ADRs
-P450 interactions -diarrhea -inc cholesterol -HA -shingles -inc creatinine phosphokinase -nasopharyngitis -rash -URI -rare: -malignancy -serious infection (TB) -anemia -neutropenia -hypersensitivity -tofacitinib: black box for inc mortality -upadactitinib: teratogenicity, secreted in breast milk
63
Tofacitinib black box warning
-JAK inhibitor -inc mortality, CV events, and thrombosis in RA pt >50 w at least one CV risk factor
64
Upabacitinib ADR
-JAK inhibitor -teratogenicity -secreted in breast milk =avoid in preg and lactation
65
JAK monitoring
-baseline only: -CXR, PPD -Hep B,C -baseline + maintenance: -ANC q3mo -CBC q1-2mo then q3mo -lipids q1-2mo after start, periodically -LFTs "" -renal fx periodically -infection s/sx -skin exam
66
S1P inhibitor drugs + MOA
-ozanimod -estrasimod -prevent lymphocyte mobilization to inflammatory sites -UC only -oral
67
S1P use + CI
-UC only -AVOID w immunosuppressive or immune-modulating drugs -CI in: -CV, TIA in last 6 months -Class III-IV HF -cardiac conduction abnormalities -severe sleep apnea (ozanimod) -MAOI (ozanimod)
68
Ozanimod considerations
-CI: -sleep apnea -MAOI =active metabolite of ozanimod is MAO-B inhibitor
69
S1P inhibitor ADRs
-inc risk of infection -PML -get vax, avoid live vax (1mo before or 3mo after) -bradycardia/conduction delays -liver injury (avoid in hepatic impairment) -inc BP -resp effects (avoid ozanimod in sleep apnea) -macular edema -reversible posterior leukeoencephalopathy syndrome (RPLS) -P450 interactions -MAO interactions (ozanimod)
70
S1P drug interactions
-P450 -MAOI (ozanimod)
71
S1P monitoring
-baseline only: -CXR, PPD -HEP B, C -ECG -baseline + maintenance: -CBC -LFTs -infection s/sx (+for 3mo d/c) -BP each visit -spirometry if needed -optho regularlly
72
Antimicrobial drugs for IBD
-ciprofloxacin -metronidazole -rifamycin antibiotics
73
Antimicrobial use IBD
-adj tx of complications -may use in CD associated fistulas/abscesses, perianal involvement, post resection -little efficacy in tx luminal disease, generally not recommended
74
Antimicrobial ADRs
-agent specific -resistance -C.diff
Therapeutics III
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