Pharm - Tx for IBD Flashcards
What are the 4 familial agents used to treat UC?
- 5-ASA
- JAK inhibitors
- TNF-a inhibitors
- a4 Integrin inhibitors
sulfasalazine
mesalamine
olsalazine
balsalazide
5-ASA’s
tofacitinib
JAK inhibitor
adalimumab
golimumab
infliximab
TNF-a inhibitors (for UC)
vedolizumab
a4 integrin inhibitor
what are the 3 familial agents used to treat Crohn disease?
- IL-12/23 inhibitors
- TNF-a inhibitors
- a4 integrin inhibitors
ustekinumab
IL-12/23 inhibitor
adalimumad
certolizumab
infliximab
TNF-a inhibitors (for CD)
natalizumab
vedolizumab
a4 integrin inhibitors
what is the MOA of 5-ASA agents?
inhibit prostaglandin and leukotriene production via arachidonic acid pathway
- may also inhibit the activation of NF-kb, regulating transcription of pro-inflammatory proteins
what drug is sulfapyridine + 5-ASA?
sulfasalazine
- sulfa is carrier molecule, 5-ASA provides antimicrobial property
- watch for sulfa allergy!
which drug is a single 5-ASA?
mesalamine
which drug is 2 molecules of 5-ASA?
olsalazine
which drug is an inert carrier + 5-ASA? why is this drug important?
balsalazide
- don’t have to worry about sulfa allergy with an inert carrier!
which form of 5-ASA may be released in the distal/terminal ileum, colon, or throughout GI tract?
oral form
which form of 5-ASA may reach the splenic flexure and does not concentrate in the rectum?
rectal enemas
what form of 5-ASA can reach the upper rectum (15-20cm beyond the anal verge)?
rectal suppositories
what are the side effects of 5-ASA agents?
- dizziness, headache, fatigue
- epigastric distress (anorexia, abd pain, NVD)
what drug drug is contraindicated in sulfonamide-allergic patients?
sulfasalazine
what are the indications for 5-ASA agents?
mild-moderate UC
what are the exceptions for 5-ASA indications?
- olsalazine is ONLY used for maintenance of remission
- balsalazine is ONLY used for active disease (not remission)
this drug binds to and neutralizes membrane associated TNF-a mediated pro-inflammatory cell signaling, ultimately blocking leukocyte migration to site of inflammation
TNF-a inhibitor
recombinant IgG1 monoclonal Ab
adalimumab
chimeric (murine/human) IgG1 monoconal Av
infliximab
recombinant humanized IgG4 monoclonal Ab
golimumab
recombinant humanized Ab fragment
certolizumab
NOTE: does NOT contain an Fc region, thus does NOT fix complement or cause Ab-dependent cell-mediated cytotoxicity
what two TNF-a inhibitors are approved for both UC and CD? (moderate-severe)
adalimumab and infliximab
think of additive and inclusive!
what TNF-a inhibitor is approved only for moderate-severe CD?
certzolizumab
what TNF-a inhibitor is approved only for moderate-severe UC?
golimumab
what is the main side effect of TNF-a inhibitors?
infection -> MUST do Tb testing pre-therapy (to make sure they don’t have quiescent disease)
NOTE: TNF-a inhibitors are used after pt does not respond to conventional immunosuppressant therapy
what is the black box warning of TNF-a inhibitors?
discontinue if pt develops serious infection or sepsis
- active Tb, invasive fungal infections, bacterial, or viral
what are the side effects of TNF-a inhibitors?
- *infections!**
- liver toxicity
- headache/arthralgias/fatigue
which TNF-a inhibitor is administered subQ every 2 weeks?
adalimumab
which TNF-a inhibitor is administered via IV infusion every 8 weeks?
infliximab
one that starts with I -> given IV
which TNF-a inhibitors are administered subQ every 4 weeks?
golimumab AND certolizumab
this drug limits integrin-associated cell adhesion and subsequent trans-endothelial migration of leukocytes to the cite of inflammation
a4 integrin inhibitors
NOTE: a4 integrin inhibitors are used after pt does not respond to conventional immunosuppressant OR TNF-a therapy
this drug is a recombinant humanized IgG4 monoblonal Ab a4B1 (VCAM-1) and a4B7 (MAdCAM-1)
natalizumab
this drug is a humanized IgG1 monoclonal Ab
** a4B7 (MAdCAM-1) ONLY
vedolizumab
which a4 integrin inhibitor is used to treat both UC and CD? (moderate-severe)
vedolizumab
which a4 integrin inhibitor is only used to treat moderate-severe CD, but can bind to both a4B1 and a4B7 receptors?
natalizumab
what is the main side effect of a4 integrin inhibitors?
- *infections**
- black box warning for the risk of progressive multifocal leukoencephalopathy (PML) while taking natalizumab
what are the 3 risk factors for PML?
- a4 integrin treatment >2 years
- prior immunosuppressant treatment
- anti-JC virus (JCV) antibodies
which a4 integrin inhibitor is administered by IV every 4 weeks?
natalizumab
which a4 integrin inhibitor is administered by IV every 8 weeks?
vedolizumab
these drugs bind to P40-subunit of IL-12/23, blocking activation/differentiation of naive T cells, and activation of NK cells
- thereby inhibiting production of pro-inflammatory cytokines (Th1, TNFa, IL17, IL21)
interleukin (IL-12/23) inhibitors
fully human IgG1 monoclonal Ab, administered subQ every 8 weeks, after single IV infusion for induction
ustekinumab
what are the side effects of IL-12/23 inhibitors?
- *infections!**
- Tb testing recommended pre-therapy
also infusion/injection reactions, HA, arthralgia, fatigue
which drug is used to treat moderate-severe CD, and is reserved for patients intolerant or inadequate response (resistant) to conventional, immune modulators, steroids or TNF-a therapy)
ustekinumab
these drugs bind to and inhibit free-floating and bound JAK-1 and JAK-3, ultimately inhibiting gene transcription and more cytokine release
JAK inhibitors
which drug is an oral JAK 1/3 inhibitor used to treat moderate-severe UC?
tofacitinib
- PO 2x/day
what are the side affects of tofacitinib?
- lymphopenia/lymphocytosis (know baseline values before starting tx)
- neutropenia
- fatigue
- increases in LDL and HDL
NOTE: concomitant use of potent immunosuppressant therapy NOT recommended
what drug type is the most common/powerful anti-inflammatory agent?
steroids!
what are the indications for steroids?
acute and/or severe UC AND CD, that is uncontrolled by other conventional medications
NOTE: used for maintenance of remission unless absolutely required (don’t want to become steroid dependent)
what is the dosing of steroid agents for UC and CD?
the LOWEST dose for the SHORTEST duration possible
- not good to be on steroids for extended time