IBD Pharmacology

What is the MOA of mesalamine derivates?

act topically in GI tract to reduce inflammation; decreased prostaglandins and proinflammatory cytokines through COX inhibition

What is sulfasalzine?

mesalamine + sulfa carrier

colonic bacteria cleave bacteria off so it only works in the colon

What are the ADRs of sulfasalazine?

caused by sulfa: GI, rash, photosensitivity, blood dyscrasias

What is the dosing of sulfasalazine?

QID

What is the brand name of olsalzine?

Dipentum

What is olsalzine?

two mesalamine linked together

cleaved apart by colonic gut bacteria

True or False: olsalzine is better tolerated sulfasalazine

true

What ADR does olsalzine have?

diarrhea

What is the dosing for olsalzine?

BID

What is the brand name of balsalazide?

Colazal

What is balsalazide?

sulfasalazine without the sulfa

cleaved but colonic gut bacteria into mesalamine + inert carrier

Which mesalamine derivative is the best tolerated?

balsalazide

What is the dosing for balsalazide?

TID

What kind of release is mesalamine?

delayed/controlled release

True or False: mesalamine is better tolerated then its derivatives

true

What is an acute intolerance/allergy to mesalamine?

diarrhea, fever, pain, usually 1-3 weeks after starting therapy; some can tolerate alternate mesalamine products, but some cannot

What mesalamine product reaches the rectum?

mesalamine suppository

What mesalamine product reaches the distal colon?

mesalamine enema

What mesalamine product reaches to the proximal colon/terminal ileum?

apriso, balsalazide, olsalazine

What meselamine product reaches to the jejunum?

pentasa

What medications are mesalamine derviatives?

sulfasalazine, olsalzine, balsalazide

What medications are immunomodulators?

thiopurines (azathiprine, 6-mercaptopurine)

methotrexate

How long do immunomodulators take to reach full effect?

~12 weeks

What role in therapy do immunomodulators have?

• maintenance of remission

• decrease in biological formation (in TNF-alpha biologics)

What is the dosing of azathioprine and 6-mercaptopurine?

daily

What is the route of azathioprine and 6-mercaptopurine?

oral

True or False: thiopurines are steroid sparing

true

What does steroid sparing mean?

a medication used to help patients stop taking steroids

What is the MOA of azathioprine and 6-mercaptopurine?

inhibition of DNA synthesis

apoptosis of activated T cells

inhibition of T cell proliferation

True or False: thiopurines get incorporated into DNA and RNA

true

What is the dosing of methotrexate?

weekly

What is the route of methotrexate?

IM or SQ

What is the MOA of methotrexate?

inhibits folate synthesis causing decreased cell replication and decreased lymphocytes and cytokines

What monitoring should be done for someone on thiopurine immunomodulators?

TPMP testing, CBC, LFTs, pancreatic enzymes, lymphoma

What monitoring should be done for someone on methotrexate?

CBC, LFTs

What does low TPMP mean for someone on thiopurines?

increased risk of side effects; should decrease the dose

What is the MOA of corticosteroids?

broad anti-inflammatory and immune suppression

How long does it take for corticosteroids to take effect?

hours to days

Which brand name of budesonide is used in Chron’s because it releases in the ileum?

Entocort

Which brand name of budesonide is used in ulcerative colitis because it releases in the colon?

uleris

What are examples of anti-TNFs?

infliximab, adalimumab

What is the brand name of infliximab?

Remicade

What is the brand name of adalimumab?

Humira

What are examples of selective adhesion molecule (integrin) inhibitors?

natalizumab, vedolizumab

What is the brand name of natalizumab?

Tysabri

What is the brand name of vedolizumab?

Entyvio

What are examples of Il-12, IL-23 inhibitor, p40?

ustekinumab

What is the brand name of ustekinumab?

Stelara

What are examples of IL-23 inhibitor, p19?

risankizumab, guselkumab

What is the brand name of risankizumab?

Skyrizi

What is the brand name of guselkumab?

Tremfya

What are examples of JAK inhibitors?

upadacitinib

What is the brand name of upadacitinib?

Rinvoq

What are examples of S1PR modulators?

ozanimod

What is the brand name of ozanimod?

Zeposia

Which selective adhesion molecule inhibitor is GI specific (and used more)?

vedolizumab

Which interleukin is more specific and central to IBD pathogenesis?

IL-23

What are JAK inhibitors?

Janus kinase are intracellular enzymes that transmits signals arising from cytokines that influence hematopoiesis & immune cell function; inhibition leads to decreased cytokines

What is the route of infliximab?

Induction: IV

Maintenance: IV or SQ

What is the route of adalimumab?

SC

True or False: infliximab has a biosimilar available

true

True or False: adalimumab has a biosimilar available

true

What is the route of vedolizumab?

Induction: IV

Maintenance: IV or SQ

What is the route of ustekinumab?

Induction: IV

Maintenance: SQ

True or False: ustekinumab has biosimilars available

true

What is the route of risankizumab?

Induction: IV

Maintenance: SC

What is the route of guselkumab?

Induction: IV or SQ

Maintenance: SC

What is the route of upadacitinib?

PO

What is the route of ozanimob?

PO

What is the route of natalizumab?

IV (SQ not approved in US)

True or False: natalizumab has biological similars available

true

What is the MOA of S1PR1 modulators?

S1P gradients lymphocyte sequestration in lymph node (doesn’t go out to the inflamed tissues)

What symptoms occur in an acute infusion related reaction?

headache, dizziness, nausea, flushing, fever, chest pain, pruritis

What ADRs do biologics have?

infusion related reactions (IV only)

injection site reactions (SQ)

infection risk

What can you do to limit the risk of infusion related reactions?

slow the infusion down, pre-medicate with Tylenol, Benadryl, steroids

What symptoms occur in a delayed infusion related reactions?

myalgias, arthralgias, fever, rash, urticaria

What could you use to treat a delayed infusion related reaction?

short course of steroids

What types of infections are people on biologics at risk for?

bacterial, TB, viral, invasive fungal infections

What needs to be done prior to starting biologics due to the risk of infections?

TB test and chest x-ray

all live/live attenuated vaccines (1 month prior)

True or False: biologics therapy should be held if a serious infection arises

true

What is the BBW for anti-TNFalpha biologics?

malignancy (mostly lymphomas)

True or False: thiopurines lower the risk of malignancy when used with anti-TNFalpha biologics?

false

What is the BBW of natalizumab?

progressive multifocal leukoencephalopathy (PML)

What is PML?

reactivation of the JC virus which can lead to CNS infections that are often fatal

True or False: natalizumab can not be given with other immunotherapies

true

True or False: natalizumab requires a mandatory prescribing program

true

What is the BBW of inflizimab?

heart failure or risk of worsening HF

What is a contraindication of S1PR1s?

ADHF or recent MI due to risk of bradyarrythmias

What ADRs do JAK inhibitors specifically have?

BBW: cancer, CV events, thrombosis, death

True or False: JAK inhibitors are limited to patients who have not responded or can not tolerate an anti-TNF alpha therapy

true

What specific ADRs do S1PR1 modulators have?

CV effects, brady arrythmias, orthostatic hypotension with 1st dose but hypertension with chronic use, PML, hepatotoxicity

What antibiotics are used in IBD for fistulas?

metronidazole ± 3rd generation cephalosporins or ciprofloxacin for a 1 week course

True or False: infliximab is not good for fistulas

false