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GI II Final > IBD Pharmacology > Flashcards

IBD Pharmacology Flashcards

1
Q

Classes of drugs used for UC

A

5-ASA
JAK inhibitors
TNF-alpha inhibitors
Alpha-4 integrin inhibitors

[steroids, immune modulators, and abx are also utilized as first-line therapy but not officially indicated]

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2
Q

Classes of drugs used for Crohns

A

IL-12/23 inhibitors
TNF-alpha inhibitors
Alpha-4 integrin inhibitors

[steroids, immune modulators, and abx are also utilized as first-line therapy but not officially indicated]

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3
Q

MOA of 5-ASA agents

A

Inhibition of prostaglandin and leukotriene production via arachidonic acid pathway [inhibits enzymes COX and LIPOX] —> reduction in PMN and macrophage chemotaxis

[may also inhibit activation of NFkB, thus regulating transcription for pro-inflammatory proteins]

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4
Q

Structural ingredients and indications for sulfasalazine

A

Sulfapyridine + 5-ASA

Active cases and maintenance of remission for mild-to-moderate UC

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5
Q

Structural ingredients and indications for Mesalamine

A

Single 5-ASA

Active cases and maintenance of remission for mild-to-moderate UC

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6
Q

Structural ingredients and indications for Olsalazine

A

2 molecules of 5-ASA

Maintenance of remission of mild-to-moderate UC

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7
Q

Structural ingredients and indications for Balsalazide

A

Inert carrier + 5-ASA

Active cases of mild-to-moderate UC

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8
Q

Side effects of 5-ASA agents

A

Dizziness, headache, fatigue

Epigastric distress (anorexia, abdominal pain, N/V/D)

There are fewer systemic SEs with pure 5-ASA products (non-sulfasalazine) and topical formulations

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9
Q

Contraindications to 5-ASA agents

A

All 5-ASA compounds are contraindicated in ASA-allergic patients

Sulfasalazine is contraindicated in sulfonamide-allergic patients

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10
Q

MOA of TNF-alpha inhibitors

A

Binds to and neutralizes membrane-associated and soluble human TNF-alpha mediated pro-inflammatory cell signaling, ultimately blocking leukocyte migration to site of inflammation

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11
Q

TNF-alpha inhibitors used for IBD

A

Adalimumab
Infliximab
Golimumab
Certolizumab

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12
Q

Unique feature of certolizumab

A

Does not contain a fragment crystallizable (Fc) region, thus does not fix complement or cause Ab-dependent cell-mediated cytotoxicity

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13
Q

Side effects of TNF-a inhibitors

A

Infections [must test for TB prior to initiating therapy, since latent infection could be reactivated]

Liver toxicity (increased ALT and AST)

Headache, arthralgias, fatigue

Rare but severe side effects include dermatologic (EM, SJS, TEN) or various malignancies

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14
Q

Indications for adalimumab

A

Active cases and maintenance of remission for moderate-to-severe UC and CD

[maintenance dose administered SQ every 2 weeks]

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15
Q

Indications for Infliximab

A

Active cases and maintenance of remission for moderate-to-severe UC and CD

[maintenance dose administered IV every 8 weeks]

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16
Q

Indications for Golimumab

A

Active cases and maintenance of remission for moderate-to-severe UC

[Maintenance dose administered SQ every 4 weeks]

17
Q

Indications for Certolizumab

A

Active cases and maintenance of remission for moderate-to-severe CD

[maintenance dose administered SQ every 4 weeks]

18
Q

T/F: All TNF-alpha inhibitors are used in cases of IBD after inadequate response to conventional or immunosuppressant therapy

A

True

19
Q

MOA of alpha-4 integrin inhibitors

A

Limits integrin’s associated cell adhesion and subsequent transendothelial migration of leukocytes to site of inflammation

20
Q

Alpha-4 integrin inhibitors used for IBD

A

Natalizumab (recombinant humanized IgG4k monoclonal Ab)

Vedolizumab (humanized IgG1 monoclonal Ab)

21
Q

Side effects of alpha-4 integrin inhibitors

A

Infections [Natalizumab associated with Progressive Multifocal Leukoencephalopathy d/t JCV]

Infusion reactions

Anti-medication antibodies (decrease efficacy)

Rare SE of Vedolizumab is increased risk of malignancy

22
Q

Natalizumab is associated with risk of developing Progressive Multifocal Leukoencephalopathy d/t JCV. What are 3 risk factors for developing PML during course of tx?

A

Treatment >2 years

Prior immunosuppressant tx

Anti-JC virus antibodies

23
Q

Indications for Natalizumab

A

Active cases and maintenance of remission of moderate-to-severe CD

[note that it is not recommended in combination with immunosuppressants, including TNF-alpha agents]

—maintenance dose administered IV every 4 weeks

24
Q

Indications for Vedolizumab

A

Active cases and maintenance of remission of moderate-to-severe UC and CD

—maintenance dose administered IV every 8 weeks

25
Q

T/F: all alpha-4 integrin inhibitors are used for IBD after inadequate response to conventional or TNF-alpha therapy

A

True

26
Q

MOA of IL-12/23 inhibitors

A

Bind to P40-subunit of IL-12 and IL-23, blocking activation and differentiation of naive T cells and activation of NK cells —> inhibits production of pro-inflammatory cytokines

27
Q

IL-12/23 inhibitor indicated for IBD

A

Ustekinumab (fully human IgG1k monoclonal Ab)

28
Q

SEs associated with IL-12/23 inhibitors

A

Infections [must get TB test prior to therapy initiation]

Infusion/injection-related allergic reactions

Headache, arthralgias, fatigue

Rare SE is increased risk of malignancy

29
Q

Indications for IL-12/23 inhibitor

A

Active cases and maintenance of remission for moderate-to-severe CD

[for patients intolerant or inadequate response/resistance to conventional, immune modulators, steroids, or TNF-a therapy]

—administered IV as single infusion for induction, then SQ every 8 weeks for maintenance

30
Q

MOA of JAK inhibitors used for IBD

A

Bind to and inhibit free-floating and bound JAK-1 and JAK-3 (lesser extent JAK-2)

Ultimately inhibit gene transcription and more cytokine release

31
Q

JAK-inhibitor indicated for IBD use

A

Tofacitinib (oral JAK-1/-3 inhibitor)

32
Q

SE’s of Tofacitinib (JAK inhibitor)

A

Lymphopenia/lymphocytosis

Neutropenia/anemia

Fatigue

Increases in LDL and HDL (minimal ratio change)

Rare SE is increased risk of malignancies/serious infections

33
Q

Indications for JAK-inhibitors use in IBD

A

Active cases and maintenance of remission for moderate-to-severe UC

[concomitant use of biologic therapies or potent immunosuppressants not recommended]

—administered PO BID

34
Q

Indications for using steroid agents for IBD

A

Acute and/or SEVERE UC and CD that is uncontrolled by other conventional medications — not used for maintenance of remission unless absolutely required

Must use the lowest dose for shortest duration possible

GI II Final (8 decks)

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