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PHRM 864 therapeutics > IBD Therapeutics > Flashcards

IBD Therapeutics Flashcards

1
Q

What are the ASAs for IBD

A

sulfasalazine, mesalamine

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2
Q

What steroids are used for IBD

A

local and systemic

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3
Q

what are the immunomodulators used for IBD

A

azathioprine, mercaptopurine, cyclosporine, methotrexate

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4
Q

what are the anti-tnf-a agents used in IBD

A

infliximab, adalimumab, certolizumab, golimumab

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5
Q

what are the other anti inflammatory agents for IBD

A

natalizumab, vedolizumab, ustekinumab

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6
Q

what is the active component of sulfasalzine

A

5-ASA
exerts actions locally

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7
Q

mesalamine is absorbed where in the GI

A

rapidly absorbed in small intestine but not colon

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8
Q

formulations of mesalamine

A

topical
suppository
oral

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9
Q

ADRs of sulfasalazine

A

N/V, headache, anorexia, rash, anemia, hypersensitivity

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10
Q

what is the major DDI with sulfasalazine

A

antiplatelet/anticoag/NSAIDs all may increase bleeding risk

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11
Q

ADRs of mesalamine

A

more tolerated than sulfasalazine
N/V, headache, diarrhea, rash

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12
Q

DDI with mesalamine

A

antiplatelet/anticoag/nsaids all may increase bleeding risk
PPI, H2RA, antacids could all influence release of drug

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13
Q

Budesonide class and MOA

A

corticosteroids and anti inflammatory

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14
Q

what is the budesonide formulation for IBD

A

PO in CR formulation

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15
Q

how long can you use corticosteroids in IBD

A

8-16 weeks

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16
Q

what are the DDIs with budesonide

A

CYP3A4 inhibitors (ketoconazole, grape fruit juice)

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17
Q

what are the ADRs of all corticosteroids

A

short term: hyperglycemia, gastritis, mood changes, increased BP
long term: aseptic necrosis, cataracts, obesity, growth failure, HPA suppression, osteoporosis

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18
Q

what other corticosteroids besides budesonide can be used for IBD

A

oral prednisone or prednisolone
IV methylprednisolone or hydrocortisone
can be used for disease flares or induction of remission

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19
Q

when to use azathioprine (AZA) and mercaptopurine (MP, 6-MP)

A

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

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20
Q

can you use AZA or MP for induction?

A

no but it can maintain remission

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21
Q

can you use AZA/MP with other drugs

A

yes

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22
Q

when can you see the benefit of AZA/MP

A

weeks to months

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23
Q

What are the ADRs of AZA and 6-MP

A

N/V/D, anorexia, stomatitis
bone marrow suppression
hepatotoxicity
fever, rash, arthralgia, pancreatitis

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24
Q

what is the monitoring for AZA/MP

A

TMPT must be taken prior to start
CBC
LFTs

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25
Q

when to use cyclosporine

A

inducing remission in patients with refractory IBD
not an option for long term use

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26
Q

ADRs of cyclosporine

A

nephrotoxicity
neurotoxicity
HTN, hyperlipidemia, hyperglycemia
GI upset, hirsutism

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27
Q

monitoring of cyclosporine

A

BP, BUN/SCr, LFTs, trough concentration

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28
Q

what are the DDIs with cyclosporine

A

increase conc: azoles, anti-fungals, macrolide antibiotics, CCBs, grapefruit
decrease conc: phenytoin, rifampin

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29
Q

When to use methotrexate

A

crohn’s disease for maintenance

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30
Q

what are the ADRs of methotrexate

A

bone marrow suppression (add folic acid)
N/V/D, stomatitis, mucositis
cirrhosis, hepatitis, fibrosis
hypersensitivity pneumonitis
derm effects
teratogenic (need contraception)

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31
Q

when is methotrexate contraindicated

A

pregnancy
pleural effusions
chronic liver disease
immunodeficiency
blood issues
ClCr < 40 ml/min

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32
Q

monitoring for methotrexate

A

CXR
CBC
SCr
LTFs

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33
Q

what is the class and indication for infliximab (remicade)

A

anti TNF-alpha
CD and UC

34
Q

what is the class and indication for adalimumab (humira)

A

anti TNF-alpha
CD and US

35
Q

what is the class and indication for golimumab (simponi)

A

anti TNF-alpha antibody
UC

36
Q

what is the class and indication for certolizumab pegol (Cimzia)

A

anti-TNF alpha
CD

37
Q

what is the class and indication for Natalizumab (Tysabri)

A

anti alpha integrin
CD

38
Q

what is the class and indication for vedolizumab (entyvio)

A

anti a4B7 integrin
UC and CD

39
Q

what is the class and indication for ustekinumab (stelara)

A

IL-12 and IL-23 antagonist
CD and UC

40
Q

what is the class and indication for risankizumab-rzaa (skyrizi)

A

IL-23 antagonist
CD and UC

41
Q

what is the class and indication for mirikizumab (Omvoh)

A

IL-23 antagonist
UC

42
Q

what is the class and indication for tofacitinib (xeljanz)

A

oral JAK inhibitor
UC

43
Q

what is the class and indication for upadacitinib (Rinvoq)

A

oral JAK 1 inhibitor
UC and CD

44
Q

What is the class and indication for ozanimod (Zeposia)

A

oral S1P receptor modulator
UC

45
Q

what is the class and indication for estrasimod (Velsipity)

A

oral s1p receptor modulator
UC

46
Q

What are the class ADRs of anti-TNF-alpha

A

-increased risk of infection
-CI of live vaccines during tx and 3 months after
-injection site rxn
-risk of malignancy/lymphoma
-demyelinating disease
-exacerbation of CHF

47
Q

baseline monitoring for Anti-TNF-alpha

A

-CXR, PPD
-infection
-UA
-CBC
-SCr, lytes
-LFTs
-Hep B, C

48
Q

maintenance monitoring for anti-TNF-alpha

A

infections
UA
CBC
SCr, Lytes
LFTs
inflammatory markers

49
Q

when to use infliximab

A

mod-sev CD and UC
induction and maintenance

50
Q

how to prevent development of ADAs in biologics

A

combine with azathioprine, but could increase ADRs

51
Q

when to use adalimumab

A

mod-sev CD and UC
induction and maintenance therapy

52
Q

when to use golimumab

A

mod-sev UC
induction and maintenance

53
Q

when to use certolizumab

A

mod-sev CD
induction and maintenance

54
Q

when to use natalizumab

A

CD
induction and remission
used in pts who fail or do not tolerate TNF-alpha

55
Q

when do d/c natalizumab

A

d/c if not working

56
Q

what is associated with natalizumab that is severe

A

Progressive Multifocal Leukoencephalopathy (PML)

57
Q

when to use vedolizumab

A

UC and CD
induction and remission

58
Q

ADR of vedolizumab

A

biologic ADRs
less association with PML
TDM possible

59
Q

when to use ustekinumab

A

CD and UC
induction (IV) and maintenance (SQ)

60
Q

severe ADR associated with ustekinumab

A

carcinomas of the skin (get regular skin exams)

61
Q

when to use risankizumab (Skyrizi)

A

mod-sev CD and UC
induction (IV) and maintenance (SQ)

62
Q

ADRs of risankizumab

A

biologic ADRs
increase of LFTs
increase of lipids

63
Q

when to use mirikizumab

A

UC
induction and maintenance

64
Q

ADRs of mirikizumab

A

biologic ADRs
increase of LFTs and lipids

65
Q

Why should TDM be tested

A

determines conc and drugs and ADA in body
consider doing TDM if loss of treatment response

66
Q

If there is subtherapeutic drug levels and detectable ADA, what is the cause and what should you do?

A

The cause is an immune mediated PK issue
change to alternate drug within same class

67
Q

If there is subtherapeutic drug levels and undetectable ADAs, what is the cause and what should you do?

A

Non-immune mediated PK issue
increase the dose

68
Q

If there are therapeutic drug levels and detectable ADAs, what is the cause and what should you do?

A

Either a false positive or mechanistic failure
repeat TDM or switch to out of class biologic

69
Q

If there are therapeutic drug levels and undetectable ADAs, what is the cause and what should you do?

A

Mechanistic failure
Switch to out of class biologic agent

70
Q

when to use tofacitinib

A

UC only for pts who have inadequate response to or intolerant to TNF blockers

71
Q

what are ADRs for tofacitinib

A

common: diarrhea, elevated cholesterol, headache, shingles, rash
rare: malignancy, infection, neutropenia

72
Q

black box warning for tofacitinib

A

increased mortality for RA patients 50+ with at least one CV risk factor
increased thrombosis for those patients

73
Q

when to use upadacitinib

A

UC and CD for pts who have inadequate response to or intolerant to TNF blockers

74
Q

black box warning for upadacitinib

A

same warning as tofacitinib

75
Q

ADR for upadacitinib for young women

A

potentially teratogenic, excreted in breast milk

76
Q

when to use ozanimod

A

mod-sev active UC
used alone

77
Q

what is the dosing catch with ozanimod

A

if a dose is missed in the first two weeks of tx, reinitiate titration regimen

78
Q

what are the CI for ozanimod

A

MACE in last 6 months
mobtiz type II
severe or untreated sleep apnea
taking MAO inhibitor

79
Q

what are the ADRs of ozanimod

A

increased risk of infection
bradycardia/AV conduction delays

80
Q

when to use estrasimod

A

mod-sev UC

81
Q

what are CI to estrasimod

A

MACE in last 6 months
cardiac conduction abnormalities

PHRM 864 therapeutics (14 decks)

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