IBD drugs Flashcards
indications for 5-ASA
induction and maintenance of remission ulcerative colitis, limited role in crohn’s
indications for corticosteroids
induction of remission in ulcerative colitis and crohn’s, not for maintenance
indications for thiopurines
maintenance of remission in ulcerative colitis and crohn’s, not appropriate for induction
indications for methotrexate
maintenance for crohn’s only, no benefit for ulcerative colitis
indications for cyclosporine
induction of remission in ulcerative colitis
indications for tacrolimus
induction of remission in ulcerative colitis and fistulizing crohn’s
indications for infliximab and adalimumab
induction and maintenance of remission in ulcerative colitis and crohn’s
indications for certolizumab
induction and maintenance of remission in crohn’s
indications for golimumab
induction and maintenance of remission in ulcerative colitis
indications for natalizumab
induction and maintenance of remission in crohn’s
indications for vedolizumab
induction and maintenance of remission in crohn’s and ulcerative colitis
indications for ustekinumab
induction and maintenance of remission in crohn’s and ulcerative colitis
indications for tofacitinab
induction and maintenance of remission in ulcerative colitis
5-ASA mechanism
anti-inflammatory: inhibit IL-1, TNFa, lipoxygenase, NFkB, scavenging of free radicals and oxidants
5-ASA adverse
sulfa allergic reaction, male infertility (reversible), inhibits folic acid synthesis (anemia, supplement), nephrotoxicity rare
5-ASA dosing
4x daily dosing, higher dose for induction
counseling points for 5-ASA
take with food, urine discoloration, avoid acid-suppressing medications if taking the pH sensitive tablets
corticosteroids mechanism
anti-inflammatory, immunosuppressive, glucocorticoid receptor binding
which corticosteroid minimizes systemic exposure
budesonide; high first pass metabolism
clinical pearls for corticosteroids
gradual tapering required, adrenal crisis, interferes with vaccines at high doses, take with food, hyperglycemia
thiopurines mechanism
metabolized into purine analogs that inhibit DNA synthesis: immunomodulators
black box warning for thiopurines
malignancy–> non-melanoma skin cancer & lymphomas
adverse for thiopurines
bone marrow suppression (leukopenia), hepatotoxicity, pancreatitis
monitoring for thiopurines
BEFORE initiating: TPMT genotype, viral hepatitis, TB
toxicity monitoring for thiopurines
6-MMP and 6-TG
counseling for thiopurines
take after meals and divide daily doses (nausea), wear sunscreen, report s/s of infection
what is not recommended with thiopurines
switching from AZA to 6-MP in treatment failure (unless mild GI upset), taking allopurinol
thiopurines take ___ for onset
weeks to months
methotrexate mechanism
dihydrofolate reductase inhibitor: inhibits DNA synthesis and cell division leading to immunosuppression
methotrexate dosage forms
sc and im (po not recommended for IBD)
methotrexate adverse affects
bone marrow suppression (leukopenia), hepatotoxicity, malignancy (lymphoma)
methotrexate black box warning
potentially fatal toxicities and fetal risk
methotrexate contraindications
pregnancy and breastfeeding category X, alcoholism, liver disease, immunodeficiency syndromes, blood dyscrasias
how to reduce risk and severity of toxicity with methotrexate
folic acid supplementation 1 mg/day
methotrexate monitoring
pregnancy test, hepatitis, HIV risk before initiation
methotrexate counseling
avoid alcohol and NSAIDs/salicylates/PPIs due to increased toxicity risk, 2 forms of birth control, report s/s of infxn
cyclosporine mechanism
calcineurin inhibitor: inhibits production and release of IL-2, immunosuppressive
cyclosporine dosage forms
po, iv
cyclosporine monitoring
drug levels
cyclosporine is used as ___ therapy
rescue therapy for severe, steroid-refractory ulcerative colitis
cyclosporine adverse effects
seizure, pneumocystis carinii pneumonia, permanent nephrotoxicity, neurotoxicity
tacrolimus mechanism
calcineurin inhibitor, thus reducing t-lymphocyte signaling and IL-2 transcription, resulting in immunosuppression
tacrolimus dosage forms
po, iv, topical
tacrolimus monitoring
thorough monitoring of trough levels
TNFa inhibitor mechanism
mAbs that bind to and inhibit TNFa, a cytokine involved in pro-inflammatory cell signalling
TNFa inhibitor dosage forms
IV infliximab, SC others
TNFa adverse effects
well tolerated, new onset/worsening CHF, BBW for risk of infection and lymphoma
TNFa contraindications
current infection. do not administer live vaccines while on TNFa therapy
do not use infliximab in a dose >5 mg/kg in which patients
NYHA Class III/IV HF
malignancy risk for TNFa inhibitors is higher with __
concomitant AZA or 6-MP, young adult males
TNFa monitoring
TB and hepatitis at baseline, s/s of HF (consider ECG if high risk)
counseling for TNFa
report s/s of infection, malignancy, rashes, or arthralgias, rotate infection site, some SQ products contain a latex needle cover (allergy)
a4 integrin antagonist moa
mAbs that bind to integrin, receptor proteins that mediate attachments of lymphocytes to endothelial cells and promote their migration into inflamed tissue
a4 integrin antagonist dosage forms
IV
which a4 integrin has a REMS program
natalizumab: REMS for PML, a debilitating fatal demyelinating brain disease
a4 integrin adverse
arthralgias, headache, pharyngitis, depression, low risk during pregnancy
a4 integrin monitoring
TB and viral hepatitis, anti-JCV antibodies (natalizumab)
a4 integrin counseling
report s/s of infection, meningitis, encephalitis, PML (natalizumab)
IL-12/23 inhibitor moa
mAb that binds p40 subunit of IL-12/23, preventing their binding to NK and T cell receptors & downregulating immune cell signaling, activation and cytokine production
IL-12/23 inhibitor dosage forms
IV first dose, subsequent doses are SQ
clinical pearl for IL-12/23 inhibitor
no increased risk for serious infections or malignancy in RCTs
IL-12/23 adverse effects
nasopharyngitis, injection site reaction, headache, low risk during pregnancy
IL-12/23 monitoring
TB and viral hepatitis screening prior to initiation
with biologics, ____ of response may occur
loss of response due to immunogenicity
which IBD drugs are biologics
TNFa inhibitors, a4 integrin antagonists, IL-12/23
which IBD drug is a small molecule
JAK inhibitor- tofacitinab
tofacitinab mechanism
preferentially inhibits JAK1 and JAK3
what are the JAK enzymes involved in
signaling pathways important for cell growth, development, survival, and differentiation
tofacitinab dosage form
po
tofacitinab black box warning
increased risk of infection and malignancy, major adverse CV events, and THROMBOSIS
tofacitinab use during pregnancy?
avoid
tofacitinab adverse
dyslipidemia, headache, nasopharyngitis
tofacitinab monitoring
TB and viral hepatitis, lipid panel
tofacitinab patient counseling
report s/s of DVT/PE, infection, malignancy, female patients avoid pregnancy while on therapy and 4 weeks after