9.21 IBD Drugs Flashcards
(26 cards)
mesalamine / 5-ASA MOA
decr NF-kB/MAPK –> decr proinflammatory cytokines
decr COX2 –> decr prostaglandins involved in inflammation
sulfasalazine pharmacokinetics
oral administration
in colon, break azo bond by bacterial azoreductase
- mes elim in feces
- sulfapyr abs and elim in urine
acetylator status important!!!
- slow acetylators have incr plasma sulfapyridine so more ADRs
sulfasalazine ADRs
inhibits folic acid synthesis
fever, malaise, NV, etc
sulfasalazine drug interactions
reduce abs of folic acid
reduce abs of dioxin
methenamine makes acidic urine, makes formaldehyde, causing crystalluria
sulfasalazine contraindications
hypersensitivity to sulfa drugs
intestinal or urinary obstruction
porphyria
use of glucocorticoids in treatment of IBD
induces remission in mod to severe UC and CD
what are the thiopurine agents
azathioprine
6-mercaptopurine
thiopurine metabolism
metabolized by TPMT into inactive compound
thiopurine MOA
6-TGN (active metabolite) incorporated into DNA and RNA , inhibiting
- cell replication
- DNA repair
- protein synthesis
a 6-TGN called 6-thio GTP binds to a Rho GTPase called Rac1
- suppress T cell APC (block immune response)
- apoptosis of activated T cells
thiopurine ADRs
bone marrow suppression!
hepatotoxicity
non melanoma skin cancer
non hodgkin lymphoma
Raynaud’s
why genotyping of thiopurine methyltransferase is recommended prior to initiation of therapy
if homozygous recessive with low activity TPMT, might have leukopenia
thiopurine drug interactions
5-ASA, sulfasalazine (inhibitors of TPMT), so incr bone marrow suppression
allopurinol (inhibit XO) so reduce metabolism of 6-MP, increase 6-TGNs, induce bone marrow suppression
situations when methotrexate used for IBD
alternate immunosuppressant (to AZA and 6-MP) for mod to severe CD if intolerant
sometimes in combo with anti-TNF
situations where cyclosporine used for IBD
induce remission (2nd line to glucocorticoid)
for severe UC unresponsive to corticosteroids
med until AZA or 6MP therapeutic levels
NOT USED FOR MAINTENANCE THERAPY b/c of SIDE EFFECTS
anti-TNF alpha mAb examples
infliximab
adalimumab
certolizumab pegol
golimumab
anti-TNF alpha mAb MOA
decreases
- inflammatory cytokines
- immune cell function
- adaptive immune response
- epithelial barrier
- MAdCAM
- MMP
compare anti-TNF alpha mAb route of admin, tx schedule, and approved uses
infliximab - IV every 8-12 weeks for CD and UC
adalimumab - SC every week for CD and UC
certolizumab pegol - SC every 4 weeks for CD
golimumab - SC every 4 weeks for UC
anti-TNF alpha mAb ADRs
common:
- URT infections
- HA
- nausea
- abd pain
- fatigue
serious:
- reactivation of TB
- infections (live vacc CI)
- heart failure
anti-TNF alpha mAb drug interactions
AZA (increases bone marrow suppression)
anakinra or abatacept (increase serious infections)
suppresses CYP450: monitor drugs with narrow therapeutic (warfarin)
anti-TNF alpha mAb loss of therapeutic effectiveness
may develop antibodies, so lose response and also have infusion reaction
anti-alpha4 mAb examples
natalizumab
vedolizumab
anti-alpha4 mAb MOA
inhibit neutrophil binding to MAdCAM (so decrease transmigration)
natalizumab: blocks a4/b7 AND a4/b1
vedolizumab: blocks only a4/b7
anti-alpha4 mAb route of admin, tx schedule, and approved uses
natalizumab: IV every 4 weeks for CD
vedolizumab: IV at 0, 2, 6, then every 8 weeks for CD and UC
anti-alpha4 mAb ADRs
PML from JC virus (esp natalizumab)
urticaria
