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PT3 GI and DERM > IBD pharmacology/therapeutics > Flashcards

IBD pharmacology/therapeutics Flashcards

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
Ustekinumab MoA
binds IL-12 and IL-23 which prevents them from activating Th1 and Th17 cells respectively
26
ustekinumab use
alternate for CD only
27
ustekinumab side effects
- injection site reactions - serious infection risk - n/v - URTIs - unknown cancer risk
28
thiopurine drugs
azathioprine | mercaptopurine
29
thiopurine MoA
- inhibit nucleic acid synthesis | - induce apoptosis in CD4 T lymphocytes
30
immunomodulator drugs
thiopurines
31
thiopurine use in therapy
- CD and UC maintenance only, not induction of remission | - use with anti-TNF and vedolizumab to reduce immunogenicity
32
how long does it take for thiopurines to be effective
3-6 months
33
thiopurine adverse effects
- myelosuppression w/ leukopenia - susceptibility to infections - pancreatitis - hepatotoxicity, nephrotoxicity - risk of lymphoma
34
TPMT
thiopurine methyltransferase
35
why test for TPMT activity
genetic polymorphisms exist that can make patients rapid or very slow metabolizers of thiopurines, increasing toxicity or reducing efficacy
36
methotrexate in IBD
alternative for induction or maintenance in mod-severe CD
37
methotrexate adverse effects
- n/v - myelosuppression (dihydrofolate reductase inh.) - increased risk of infection - hepatotoxicity - pregnancy category X
38
what do you need to take with methotrexate
folic acid to reduce typical toxicities
39
methotrexate anti-inflammatory effects due to
increase in synthesis and release of adenosine
40
how does adenosine reduce inflammation
- 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
treatment goals of CD
- stop progression - prevent complications - heal mucosa
42
initial steps in CD before starting drug treatment
- identify and treat any infections (C.diff, CMV) - stop NSAIDs - stop smoking
43
low risk CD ractors
- 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
high risk CD factors
- age at diagnosis <30 - extensive anatomic involvement - perianal and/or rectal disease present - deep ulcers - prior surgical resection - stricturing and/or penetrating behavior
45
initial CD drug treatment options of low risk patient with ileum and/or proximal colon inflammed
- budesonide 9 mg qd w/wo AZA | - tapering course of prednisone w/wo AZA
46
initial CD drug treatment of low risk patient with diffuse or left colon inflammed
tapering course of prednisone w/wo AZA
47
initial CD drug treatment options of moderately severe CD patients
- anti-TNF + thiopurine preferred - anti-TNF monotherapy - anti-TNF + methotrexate if thiopurine not tolerated
48
how long does it take to induce remission of CD
2-4 weeks
49
treatment options for low risk CD patients in remission
- stop therapy and observe - budesonide 6mg qd - immunosuppressive therapy
50
treatment options for high risk CD patients in remission
- if anti-TNF used for induction keep using +/- thiopruine | - if steroid used for induction use immunomodulator or anti-TNF
51
UC treatment goals
- induce and maintain remission - stop rectal bleeding - stop diarrhea - prevent disability, colectomy and colorectal cancer
52
initial steps in treatment of UC before starting drugs
- identify and treat infections (C.diff, CMV) - stop NSAIDs - stop smoking
53
low risk factors for colectomy
- limited anatomic extent of UC | - mild endoscopic disease
54
high risk factors for colectomy
- extensive colitis - deep ulcers - age <40 - high CRP and ESR - Hx hospitalization - C.diff or CMV infection - requires steroid
55
UC low risk treatment for induction
- oral 5ASA and/or - rectal 5ASA and/or - oral budesonide or prednisone and/or - rectal steroids
56
UC low risk treatment for maintenance
- oral 5ASA and or/ rectal 5ASA | - taper steroid over 60 days
57
UC high risk treatment options for induction
- short course of steroids w/ thiopurine - anti-TNF +/- thiopurine - vedolizumab +/- immunomodulator
58
UC high risk treatment for maintenance
- 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
5ASA indication
-induction and maintenance of low risk UC
60
5ASA efficacy
- topical are better than oral | - combo is best option though
61
5ASA suppository reach
10 cm, rectum
62
5ASA enema reach
as far as splenic flexure
63
treatment for low risk left sided UC
rectal 5ASA +/- oral 5ASA
64
treatment for low risk extensive UC
both rectal and oral 5ASA
65
5ASA onset of action
2-4 weeks
66
supplement sulfasalazine use with what
folic acid
67
sulfasalazine adverse effects
n/v dyspepsia bone marrow suppression folate deficiency
68
monitoring for 5ASAs
CBC | SCr
69
why is budesonide preferred over prednisone
less systemic ADRs
70
corticosteroid foam reach
sigmoid colon
71
supplement corticosteroid use with what
calcium and vit D
72
thiopurine monitoring
- need TPMT screen before initiating - CBC every 1-2 weeks initially, then every 3 months - hepatic panel
73
methotrexate dosing
25 mg SC or IM
74
methotrexate monitoring
baseline chest x-ray CBC hepatic panel
75
anti-TNF drugs
infliximab adalimumab certolizumab golimumab
76
anti-TNF drugs are SC injections except
infliximab, IV
77
anti-TNF drug indication
mod-high risk CD and UC | both induction and maintenance
78
when to consider anti-TNF monotherapy
high risk of ADRs - greater than 65 - male and younger than 35 years - history of cancer
79
screening to do before using anti-TNF
hepatitis B | latent TB
80
monitoring for anti-TNF drugs
CBC hepatic panel trough concentrations anti-TNF antibodies
81
if loss of response to anti-TNF, subtherapeutic level, and not Ab what do we do
increase dose | maybe add immunomodulator
82
if loss of response to anti-TNF drug, subtherapeutic leve, and high Ab what do we do
switch to another anti-TNF
83
if loss of response to anti-TNF drug and we have therapeutic level what do we do
switch to vedolizumab +/- immunomodulator
84
ustekinumab monitoring
TB screen prior to initiation
85
which surgery is considered curative for UC
proctocolectomy
86
surgery effectiveness in CD
high rate of recurrence after surgery, so not great
87
health maintenance for IBD
- colonoscopy every 1-2 years if UC or CD are extensive - skin cancer screening - osteoporosis screen if on steroids - depression and anxiety
88
vaccinations to do if using immunosuppressants
- PCV12 and PPSV23 | - Hep B and Varicella before initiation
89
drugs for IBS-C
lubiprostone | linaclotide
90
lubiprostone MoA
stimulates Cl channels in small intestine
91
lubiprostone use
only females 18 or older
92
linaclotide MoA
increases cGMP and chloride secretion
93
drugs for IBS-D
alosetron eluxadoline rifaximin
94
linaclotide counseling
take on empty stomach
95
alosetron MoA
selective serotonin antagonist
96
alosetron use
only for females | has a black box warning so use only when absolutely necessary
97
eluxadoline MoA
mixed opioid agonist
98
rifaximin MoA
antibiotic and anti-inflammatory effects

PT3 GI and DERM (8 decks)

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