Therapeutics for IBD and IBS Flashcards
GCs and UC/Crohns
Oral prednisone is the preferred
Can result in remission
Steroid refractory dz
MDR1 exp is higher in pts with CS-refractory UC
2nd line of therapy for UC/Crohns
If tapered too quickly (CSs), then can flare, at this point use 5-ASA if limited to the colon
5-ASA
Small molecule antiinflammatory drug…needs higher pH to be released
Act PPAR-gamma…suppress NFkappaB
6-mercaptopurine
Used for severe UC and for maintaining crohns in remission
Azathioprine converted to 6-MP which blocks pruine RN synthesis…inhibits lmphocyte proliferation after being incororated into DNA and inhibiting DNA replication and transcription
Inhibits the glutamune PRPP amidotransferase….also inhibits salvage pathway
TPMT test
TPMT methylates mercaptopruine and other metabolites
Methylation blocks conversion into active form….S-methylated derug inhibits diff pathway
PKs and side effects of azathio
may take effect in 6 weeks
Short term is panc and diarrhea…LT - bone marrow loss and opportunistic infections
Infliximab
Binds to TNF-alpha
Can be used for mod or severe
Infusion rxns and immune suppression
Etanercept
Fusion of TNFR2 and IgG1 Fc region…NOT effective against IBD
Ustekinumab
IL-12 and IL-23 inhibitor
IL-12 elevated in IBD and mutations of IL-23 common in IBD
Vedolizumab
AB to alpha4beta7-integrin
blocks interaction with MAdCAM-1
Selectively targets gut inflammation
UC refractory to TNF inhibitors
Additive drug effects
IBD at risk for hepatobiliary tox
Thipurines and metho can cause haptic probs
TNF inhibitors can cause TB to emerge and TB drugs hepatotoxi
5-ASA is safe during preg
Hyoscyamine
Can be used to relieve cramping
Muscarinic Ach receptor antagonists that block nervous system signling to the GI tract
Amitryptiline
Antidep for IBS
Better for those with diarrhea
