Exam 4 Flashcards
What parts of the GI tract are affected by ulcerative colitis?
rectum and colon
Does smoking have a protective effect in ulcerative colitis or Crohn’s disease?
ulcerative colitis
What drug classes may trigger disease flares in IBD?
NSAIDs and antibiotics
What drug class should generally be avoided in patients with IBD?
NSAIDs
Is enteral or parenteral nutrition used as nonpharmacologic therapy for IBD?
enteral nutrition
What are ADRs of sulfasalazine?
-N/V
-HA
-anorexia
-rash
-anemia
-hepatotoxicity
-thrombocytopenia
-hypersensitivity reactions (sulfonamide allergy)
What are monitoring parameters for sulfasalazine?
-CBC and LFTs at baseline, QOW for 3 months, QM for 3 months, then periodically
-BUN/SCr periodically
What are drug interactions with sulfasalazine?
-antiplatelets
-anticoagulants
-NSAIDs
Do sulfasalazines or mesalamines have more ADRs?
sulfasalazines
What are the formulations of mesalamine?
-topical (enema)
-suppository
-oral
For what type of ulcerative colitis are topical formulations of mesalamine used for?
left-sided disease
For what type of ulcerative colitis are suppository formulations of mesalamine used for?
proctitis
What is the specific dosage form of oral formulations of mesalamine?
delayed/controlled release
What are ADRs of mesalamine?
-N/V
-HA
What are drug interactions with mesalamine?
-antiplatelets
-anticoagulants
-NSAIDs
-agents affecting gastric pH
What is the indication of corticosteroids for use in IBD?
induction of remission
What are ADRs of systemic corticosteroids?
-hypocalcemia
-hypovitaminosis D
What are monitoring parameters for systemic corticosteroids?
occasional bone mineral density scans
What patients taking corticosteroids for IBD should be receiving occasional bone mineral density scans?
->60 y/o
-risk of osteoporosis
-using steroids for >3 months
-recurrent steroid user
What is a benefit of budesonide based on its mechanism of action?
minimal systemic exposure due to extensive first pass metabolism
Is azathioprine or mercaptopurine a prodrug?
azathioprine
What are the indications of azathioprine and mercaptopurine for use in IBD?
-fail ASA and/or refractory to/dependent on steroids
-maintenance of remission
What are ADRs of azathioprine and mercaptopurine?
-N/V
-diarrhea
-anorexia
-stomatitis
-bone marrow suppression
-hepatotoxicity
-fever
-rash
-arthralgia
-pancreatitis
What are the monitoring parameters for azathioprine and mercaptopurine?
-TPMT at baseline
-CBC and LFTs at baseline, QW for 1 month, Q1-2W after dose change, Q1-3M
What are the indications of cyclosporine for use in IBD?
-induction of remission for refractory UC
-refractory to/dependent on steroids
What are ADRs of cyclosporine?
-nephrotoxicity
-neurotoxicity
-HTN
-HLD
-hyperglycemia
-GI upset
-gingival hyperplasia
-hirutism
What are the monitoring parameters for cyclosporine?
-BP at baseline, every visit
-BUN/SCr at baseline, Q2W until stable, periodically
-LFTs at baseline, Q2W until stable, periodically
-cyanuric acid trough concentration baseline
What type of substrate is cyclosporine?
CYP3A and P-glycoprotein substrate
What is the indication of methotrexate for use in IBD?
induction of remission for CD
What are ADRs of methotrexate?
-bone marrow suppression
-N/V
-diarrhea
-stomatitis
-mucositis
-cirrhosis
-hepatitis
-fibrosis
-hypersensitivity pneumonitis
-rash
-urticaria
-alopecia
What are monitoring parameters for methotrexate?
-chest X-ray at baseline
-CBC, SCr, LFTs at baseline, Q4-8W
What are contraindications for methotrexate?
-pregnancy
-pleural effusions
-chronic liver disease/alcohol abuse
-immunodeficiency
-preexisting blood dyscrasias
-leukopenia/thrombocytopenia
-CrCl < 40 mL/min
What are the TNF-α inhibitor ADRs?
-increased risk of serious infections
-injection site reactions (SQ) and infusion related reactions (IV)
-risk of malignancy
-hepatosplenic T-cell lymphoma (HSTCL) risk
-risk of demyelinating disease
-may exacerbate CHF
-development of anti-drug antibodies
When should TNF-α inhibitors be avoided?
active infection
What monitoring parameters in regards to infections should be measured before treatment initiation?
-PPD skin test for TB
-chest X-ray
-hepatitis B and C
What is a good recommendation for TNF-α inhibitors?
ensure vaccinations are up to date
What is contraindicated during TNF-α inhibitor therapy?
live vaccines during treatment and for three months after
What patients are contraindicated for TNF-α inhibitor therapy?
-cancer
-demyelinating CNS disease
-optic neuritis
-NYHA Class III/IV HF
What are baseline monitoring parameters for TNF-α inhibitors?
-chest X-ray
-PPD skin test for TB
-s/s of infection
-urinalysis
-CBC
-SCr
-electrolytes
-LFTs
-hepatitis B and C
What baseline monitoring parameters are different from the maintenance for TNF-α inhibitors?
-chest X-ray
-PPD skin test for TB
-hepatitis B and C
What maintenance monitoring parameter is different from the baseline for TNF-α inhibitors?
inflammatory markers
How often should monitoring occur for TNF-α inhibitors?
Q8-12W
What are the indications for infliximab?
-moderate to severe active CD and UC
-induction and maintenance therapy
What is the route of administration for infliximab?
IV
What drugs can be used concomitantly with infliximab for increased efficacy?
immunosuppressives
When is there an increased HSTCL risk for infliximab?
co-administeration with azathioprine
What are monitoring parameters specific to infliximab?
-vitals
-infusion reactions
What are the indications for adalimumab?
-moderate to severe active CD and UC
-induction and maintenance therapy
What is the route of administration for adalimumab?
SQ
What are the indications for golimumab?
-moderate to severe active UC
-induction and maintenance therapy
What is the route of administration for golimumab?
SQ
What are the indications for certolizumab pegol?
-moderate to severe active CD
-induction and maintenance therapy
What is the route of administration for golimumab?
SQ
What TNF-α inhibitor has the highest risk of developing ADAs?
infliximab
What are the TNF-α inhibitor drugs?
-infliximab
-adalimumab
-certolizumab pegol
-golimumab
What is the mechanism of action of natalizumab?
anti-α subunit of integrins
What are the indications for natalizumab?
-CD
-induction and maintenance of therapy
What drugs can natalizumab not be used with?
-immunosuppressants
-TNF-α inhibitors
What is the route of administration for natalizumab?
IV
When should natalizumab be discontinued in patients?
-no benefit by 12 weeks (3 cycles) and/or
-steroid-dependent within 6 months
What is an ADR associated with natalizumab?
PML
What causes an increased risk of PML with natalizumab use?
-longer duration of therapy (> 2 years)
-prior immunosuppressant use
-JC antibody positive
What is the mechanism of action of vedolizumab?
anti-α4β77 integrin antibody
What are the indications for vedolizumab?
-CD and UC
-induction and maintenance therapy
What is the route of administration for vedolizumab?
IV
What is the mechanism of action of ustekinumab?
IL-12 and IL-23 antagonist
What are the indications for ustekinumab?
-CD and UC
-induction and maintenance therapy
What is the route of administration for ustekinumab?
SQ
What is the mechanism of action of risankizumab-rzaa?
selective IL-23 antagonist
What are the indications for risankizumab-rzaa?
-moderate to severe active CD and UC
-induction and maintenance therapy
What are the routes of administration for risankizumab-rzaa?
IV and SQ
What are common ADRs of risankizumab-rzaa?
-headache
-nasopharyngitis
-arthralgia
-abdominal pain
-anemia
-nausea
What are ADRs associated with risankizumab-rzaa?
-potential hepatotoxicity
-increase in lipids
What are baseline monitoring parameters for risankizumab-rzaa and mirikizumab-mrkz?
-chest X-ray
-PPD skin test for TB
-hepatitis B and C
-lipids
-LFTs
-renal function
-s/s of infection
What is the mechanism of action of mirikizumab-mrkz?
IL-23p19 antagonist
What are the indications for mirikizumab-mrkz?
-moderate to severe active UC
-induction and maintenance therapy
What are the routes of administration for mirikizumab-mrkz?
IV and SQ
What are common ADRs of mirikizumab-mrkz?
-headache
-arthralgia
-rash
-injection site reaction
What is an ADR associated with mirikizumab-mrkz?
potential hepatotoxicity
What criteria need to be confirmed to determine that an IBD patient is at treatment failure?
-inflammation
-exclude infection and noncompliance to treatment
-serum drug therapeutic and ADA levels
What type of treatment failure is a combination of subtherapeutic drug levels and detectable ADAs?
immune mediated pharmacokinetic failure
What is the next step of therapy for immune mediated pharmacokinetic failure?
change to alternate drug within the same class +/- immunomodulator
What type of treatment failure is a combination of subtherapeutic drug levels and undetectable ADAs?
non-immune mediated pharmacokinetic failure
What is the next step of therapy for non-immune mediated pharmacokinetic failure?
increase dose
What type of treatment failure is a combination of therapeutic drug levels and detectable ADAs?
false positive or mechanistic failure
What is the next step of therapy for a false positive?
repeat TDM levels
What type of treatment failure is a combination of therapeutic drug levels and undetectable ADAs?
mechanistic failure
What is the next step of therapy for mechanistic failure?
switch to different biologic class agent
What are the other biologic drugs?
-natalizumab
-vedolizumab
-ustekinumab
-risankizumab-rzaa
-mirikizumab-mrkz
What is the mechanism of action of tofacitinib?
JAK inhibitor
What is the route of administration for tofacitinib?
oral
What is the indication for tofacitinib?
UC
What are the clinical pearls for tofacitinib and upadacitinib?
-rapid onset
-should NOT be used with immunosuppressants or biologics
-short half-life
-eliminated via hepatic metabolism and renal excretion
How much should the dose of tofacitinib be decreased by for moderate/severe renal impairment or moderate hepatic impairment?
50%