IBD Pharmacology Flashcards
Classes of drugs used for UC
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]
Classes of drugs used for Crohns
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]
MOA of 5-ASA agents
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]
Structural ingredients and indications for sulfasalazine
Sulfapyridine + 5-ASA
Active cases and maintenance of remission for mild-to-moderate UC
Structural ingredients and indications for Mesalamine
Single 5-ASA
Active cases and maintenance of remission for mild-to-moderate UC
Structural ingredients and indications for Olsalazine
2 molecules of 5-ASA
Maintenance of remission of mild-to-moderate UC
Structural ingredients and indications for Balsalazide
Inert carrier + 5-ASA
Active cases of mild-to-moderate UC
Side effects of 5-ASA agents
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
Contraindications to 5-ASA agents
All 5-ASA compounds are contraindicated in ASA-allergic patients
Sulfasalazine is contraindicated in sulfonamide-allergic patients
MOA of TNF-alpha inhibitors
Binds to and neutralizes membrane-associated and soluble human TNF-alpha mediated pro-inflammatory cell signaling, ultimately blocking leukocyte migration to site of inflammation
TNF-alpha inhibitors used for IBD
Adalimumab
Infliximab
Golimumab
Certolizumab
Unique feature of certolizumab
Does not contain a fragment crystallizable (Fc) region, thus does not fix complement or cause Ab-dependent cell-mediated cytotoxicity
Side effects of TNF-a inhibitors
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
Indications for adalimumab
Active cases and maintenance of remission for moderate-to-severe UC and CD
[maintenance dose administered SQ every 2 weeks]
Indications for Infliximab
Active cases and maintenance of remission for moderate-to-severe UC and CD
[maintenance dose administered IV every 8 weeks]
Indications for Golimumab
Active cases and maintenance of remission for moderate-to-severe UC
[Maintenance dose administered SQ every 4 weeks]
Indications for Certolizumab
Active cases and maintenance of remission for moderate-to-severe CD
[maintenance dose administered SQ every 4 weeks]
T/F: All TNF-alpha inhibitors are used in cases of IBD after inadequate response to conventional or immunosuppressant therapy
True
MOA of alpha-4 integrin inhibitors
Limits integrin’s associated cell adhesion and subsequent transendothelial migration of leukocytes to site of inflammation
Alpha-4 integrin inhibitors used for IBD
Natalizumab (recombinant humanized IgG4k monoclonal Ab)
Vedolizumab (humanized IgG1 monoclonal Ab)
Side effects of alpha-4 integrin inhibitors
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
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?
Treatment >2 years
Prior immunosuppressant tx
Anti-JC virus antibodies
Indications for Natalizumab
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
Indications for Vedolizumab
Active cases and maintenance of remission of moderate-to-severe UC and CD
—maintenance dose administered IV every 8 weeks
T/F: all alpha-4 integrin inhibitors are used for IBD after inadequate response to conventional or TNF-alpha therapy
True
MOA of IL-12/23 inhibitors
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
IL-12/23 inhibitor indicated for IBD
Ustekinumab (fully human IgG1k monoclonal Ab)
SEs associated with IL-12/23 inhibitors
Infections [must get TB test prior to therapy initiation]
Infusion/injection-related allergic reactions
Headache, arthralgias, fatigue
Rare SE is increased risk of malignancy
Indications for IL-12/23 inhibitor
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
MOA of JAK inhibitors used for IBD
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
JAK-inhibitor indicated for IBD use
Tofacitinib (oral JAK-1/-3 inhibitor)
SE’s of Tofacitinib (JAK inhibitor)
Lymphopenia/lymphocytosis
Neutropenia/anemia
Fatigue
Increases in LDL and HDL (minimal ratio change)
Rare SE is increased risk of malignancies/serious infections
Indications for JAK-inhibitors use in IBD
Active cases and maintenance of remission for moderate-to-severe UC
[concomitant use of biologic therapies or potent immunosuppressants not recommended]
—administered PO BID
Indications for using steroid agents for IBD
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
