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PT3 GI and DERM > IBD pharmacology/therapeutics > Flashcards

IBD pharmacology/therapeutics Flashcards

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1
Q

drugs to induce remission for UC

A

5-ASA
corticosteroids
anti-TNF
anti-Integrin

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2
Q

drugs to induce remission for CD

A 
croticosteoids
anti-TNF
anti-Integrin
anti-IL 12/23
methotrexate
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3
Q

5-ASA drugs

A

mesalamine
sulfasalazine
olsalazine
balsalazide

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4
Q

mesalamine must reach where to be effective

A

the colon

-delayed release formulation is better at this

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5
Q

mesalamine rectal formulations can be used when

A

inflammation is very distal

-left sided colitis

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6
Q

sulfazalazine acts where in GI

A

colon

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7
Q

olsalazine acts where in GI

A

colon

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8
Q

5-ASA drugs mechanism of action

A

anti-inflammatory by inhibiting the action of nuclear factor kappa B, and decreased cytokines

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9
Q

additional action mesalamine has in its action

A

PPAR gamma agonist - reduce inflammation as well

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10
Q

what makes nuclear factor kappa B a good target in IBD

A

it is overactive in these diseases

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11
Q

PPAR gamma action

A

binds to NFkB, preventing it from initiating transcription and thus immune responses

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12
Q

PPAR gamma is expressed where

A

in colonic epithelial cells

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13
Q

NSAIDs and PPARgamma

A

NSAIDs activate at high antiinflammatory doses

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14
Q

mesalamine and COX enzymes

A

very weak inhibitor

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15
Q

mesalamine efficacy

A

improvement in 60-80% of patients w/ UC

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16
Q

mesalamine adverse effects

A

n/v
abdominal pain
headache
rarely interstitial nephritis

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17
Q

best mesalamine regimin

A

uses both topical and oral

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18
Q

corticosteroids MoA

A
  • decreased expression of cytokines
  • increased anti-inflammatory IL-10
  • inhibition of NFkB
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19
Q

long term use adverse effects of corticosteroids

A
  • immune suppression
  • osteoporosis
  • hypertension
  • insulin resistance/hyperglycemia
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20
Q

steroid that avoids some of the long term adverse effects

A

budensonide (Entocort)

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21
Q

antiTNF monoclonals MoA

A
  • bind up TNF alpha

- activate reverse signaling that results in death of TNF alpha expressing cells

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22
Q

adverse effects of TNF monoclonals

A
  • injection reaction
  • risk of serious infection
  • increased risk of lymphomas
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23
Q

vedolizumab MoA

A

binds to alpha4beta7 integrin on surface of T cells, which prevents binding MadCAM-1 and thus prevents T cell trafficking to the site of inflammation

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24
Q

vedolizumab adverse effects

A
  • hypersensitivity
  • increased infection risk
  • hepatotoxicity
  • arthralgias
  • cancer risk is unclear
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25
Q

Ustekinumab MoA

A

binds IL-12 and IL-23 which prevents them from activating Th1 and Th17 cells respectively

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26
Q

ustekinumab use

A

alternate for CD only

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27
Q

ustekinumab side effects

A
  • injection site reactions
  • serious infection risk
  • n/v
  • URTIs
  • unknown cancer risk
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28
Q

thiopurine drugs

A

azathioprine

mercaptopurine

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29
Q

thiopurine MoA

A
  • inhibit nucleic acid synthesis

- induce apoptosis in CD4 T lymphocytes

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30
Q

immunomodulator drugs

A

thiopurines

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31
Q

thiopurine use in therapy

A
  • CD and UC maintenance only, not induction of remission

- use with anti-TNF and vedolizumab to reduce immunogenicity

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32
Q

how long does it take for thiopurines to be effective

A

3-6 months

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33
Q

thiopurine adverse effects

A
  • myelosuppression w/ leukopenia
  • susceptibility to infections
  • pancreatitis
  • hepatotoxicity, nephrotoxicity
  • risk of lymphoma
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34
Q

TPMT

A

thiopurine methyltransferase

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35
Q

why test for TPMT activity

A

genetic polymorphisms exist that can make patients rapid or very slow metabolizers of thiopurines, increasing toxicity or reducing efficacy

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36
Q

methotrexate in IBD

A

alternative for induction or maintenance in mod-severe CD

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37
Q

methotrexate adverse effects

A
  • n/v
  • myelosuppression (dihydrofolate reductase inh.)
  • increased risk of infection
  • hepatotoxicity
  • pregnancy category X
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38
Q

what do you need to take with methotrexate

A

folic acid to reduce typical toxicities

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39
Q

methotrexate anti-inflammatory effects due to

A

increase in synthesis and release of adenosine

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40
Q

how does adenosine reduce inflammation

A
  • reduces release of TNFalpha, IL-12
  • decrease production of IL-2
  • decrease T cell proliferation
  • decrease vascular permeability
  • increases risk of antiinflammatory IL-10
41
Q

treatment goals of CD

A
  • stop progression
  • prevent complications
  • heal mucosa
42
Q

initial steps in CD before starting drug treatment

A
  • identify and treat any infections (C.diff, CMV)
  • stop NSAIDs
  • stop smoking
43
Q

low risk CD ractors

A
  • age at diagnosis >30
  • limited anatomic involvement
  • no perianal and/or rectal disease
  • superficial ulcers
  • no prior surgical resection
  • no stricturing and/or penetrating behavior
44
Q

high risk CD factors

A
  • age at diagnosis <30
  • extensive anatomic involvement
  • perianal and/or rectal disease present
  • deep ulcers
  • prior surgical resection
  • stricturing and/or penetrating behavior
45
Q

initial CD drug treatment options of low risk patient with ileum and/or proximal colon inflammed

A
  • budesonide 9 mg qd w/wo AZA

- tapering course of prednisone w/wo AZA

46
Q

initial CD drug treatment of low risk patient with diffuse or left colon inflammed

A

tapering course of prednisone w/wo AZA

47
Q

initial CD drug treatment options of moderately severe CD patients

A
  • anti-TNF + thiopurine preferred
  • anti-TNF monotherapy
  • anti-TNF + methotrexate if thiopurine not tolerated
48
Q

how long does it take to induce remission of CD

A

2-4 weeks

49
Q

treatment options for low risk CD patients in remission

A
  • stop therapy and observe
  • budesonide 6mg qd
  • immunosuppressive therapy
50
Q

treatment options for high risk CD patients in remission

A
  • if anti-TNF used for induction keep using +/- thiopruine

- if steroid used for induction use immunomodulator or anti-TNF

51
Q

UC treatment goals

A
  • induce and maintain remission
  • stop rectal bleeding
  • stop diarrhea
  • prevent disability, colectomy and colorectal cancer
52
Q

initial steps in treatment of UC before starting drugs

A
  • identify and treat infections (C.diff, CMV)
  • stop NSAIDs
  • stop smoking
53
Q

low risk factors for colectomy

A
  • limited anatomic extent of UC

- mild endoscopic disease

54
Q

high risk factors for colectomy

A
  • extensive colitis
  • deep ulcers
  • age <40
  • high CRP and ESR
  • Hx hospitalization
  • C.diff or CMV infection
  • requires steroid
55
Q

UC low risk treatment for induction

A
  • oral 5ASA and/or
  • rectal 5ASA and/or
  • oral budesonide or prednisone and/or
  • rectal steroids
56
Q

UC low risk treatment for maintenance

A
  • oral 5ASA and or/ rectal 5ASA

- taper steroid over 60 days

57
Q

UC high risk treatment options for induction

A
  • short course of steroids w/ thiopurine
  • anti-TNF +/- thiopurine
  • vedolizumab +/- immunomodulator
58
Q

UC high risk treatment for maintenance

A
  • if steroids were used continue thiopurine, or switch to anti-TNF or vedolizumab
  • if using anti-TNF or vedolizumab for induction continue using w/wo thiopurine
59
Q

5ASA indication

A

-induction and maintenance of low risk UC

60
Q

5ASA efficacy

A
  • topical are better than oral

- combo is best option though

61
Q

5ASA suppository reach

A

10 cm, rectum

62
Q

5ASA enema reach

A

as far as splenic flexure

63
Q

treatment for low risk left sided UC

A

rectal 5ASA +/- oral 5ASA

64
Q

treatment for low risk extensive UC

A

both rectal and oral 5ASA

65
Q

5ASA onset of action

A

2-4 weeks

66
Q

supplement sulfasalazine use with what

A

folic acid

67
Q

sulfasalazine adverse effects

A

n/v
dyspepsia
bone marrow suppression
folate deficiency

68
Q

monitoring for 5ASAs

A

CBC

SCr

69
Q

why is budesonide preferred over prednisone

A

less systemic ADRs

70
Q

corticosteroid foam reach

A

sigmoid colon

71
Q

supplement corticosteroid use with what

A

calcium and vit D

72
Q

thiopurine monitoring

A
  • need TPMT screen before initiating
  • CBC every 1-2 weeks initially, then every 3 months
  • hepatic panel
73
Q

methotrexate dosing

A

25 mg SC or IM

74
Q

methotrexate monitoring

A

baseline chest x-ray
CBC
hepatic panel

75
Q

anti-TNF drugs

A

infliximab
adalimumab
certolizumab
golimumab

76
Q

anti-TNF drugs are SC injections except

A

infliximab, IV

77
Q

anti-TNF drug indication

A

mod-high risk CD and UC

both induction and maintenance

78
Q

when to consider anti-TNF monotherapy

A

high risk of ADRs

  • greater than 65
  • male and younger than 35 years
  • history of cancer
79
Q

screening to do before using anti-TNF

A

hepatitis B

latent TB

80
Q

monitoring for anti-TNF drugs

A

CBC
hepatic panel
trough concentrations
anti-TNF antibodies

81
Q

if loss of response to anti-TNF, subtherapeutic level, and not Ab what do we do

A

increase dose

maybe add immunomodulator

82
Q

if loss of response to anti-TNF drug, subtherapeutic leve, and high Ab what do we do

A

switch to another anti-TNF

83
Q

if loss of response to anti-TNF drug and we have therapeutic level what do we do

A

switch to vedolizumab +/- immunomodulator

84
Q

ustekinumab monitoring

A

TB screen prior to initiation

85
Q

which surgery is considered curative for UC

A

proctocolectomy

86
Q

surgery effectiveness in CD

A

high rate of recurrence after surgery, so not great

87
Q

health maintenance for IBD

A
  • colonoscopy every 1-2 years if UC or CD are extensive
  • skin cancer screening
  • osteoporosis screen if on steroids
  • depression and anxiety
88
Q

vaccinations to do if using immunosuppressants

A
  • PCV12 and PPSV23

- Hep B and Varicella before initiation

89
Q

drugs for IBS-C

A

lubiprostone

linaclotide

90
Q

lubiprostone MoA

A

stimulates Cl channels in small intestine

91
Q

lubiprostone use

A

only females 18 or older

92
Q

linaclotide MoA

A

increases cGMP and chloride secretion

93
Q

drugs for IBS-D

A

alosetron
eluxadoline
rifaximin

94
Q

linaclotide counseling

A

take on empty stomach

95
Q

alosetron MoA

A

selective serotonin antagonist

96
Q

alosetron use

A

only for females

has a black box warning so use only when absolutely necessary

97
Q

eluxadoline MoA

A

mixed opioid agonist

98
Q

rifaximin MoA

A

antibiotic and anti-inflammatory effects

PT3 GI and DERM (8 decks)

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