IBD Flashcards
what is ibd
chronic inflammatory disorder of the Gi tract
what is indeterminate colitis
features of both crohns and ulcerative colitis
what is ulcerative colitis
disease confined to bowel wall
rectum then progresses proximally up the splenic flexure then the transverse colon and so on
only in terminal ileum, colon, and rectum
CD and UC pathophysiology
genetic predisposition with infectious and immunological responses
what is crohns disease
extensive destruction of bowel wall, invasion of adjacent tissues
any part of GI tract
crohns signs and symptoms
RLQ tenderness, painful with masses
diarrhea with low grade fever
ulcerative colitis signs and symptoms
rectal bleeding(very few things cause this so prob UC if present with this) and diarrhea no masses or specific tenderness
goals of therapy for crohns
control acute flares
induce remission
maintain remission
avoid or manage ocmplications
non drug therapy for crohns
NSAIDS - increased risk of ulcers, worsens inflammation
stop smoking helps as much as drug therapy
avoid foods that trigger
ensure proper nutrition many people wont feel like eating
may have to avoid dairy because the inflammation can cause the lactase enzyme to be shed and produce lactose intolerance
non drug therapy for UC
avoid constipating drugs - can cause the colon to expand and lose the ability to regulate your fluid balance
smoking helps
surgery in crohns
reserved for strictures and obstructions as theres an increased risk of recurrence at surgical site
ulcerative colitis surgery
cured with colectomy
some post op issues
examples of aminosalicylates
sulfasalazine
5ASA (mesalamine)
aminosalicylates MOA
prostaglandins
decreased cytokines
free radical scavenging
sulfasalazine AE
fever, fatigue, headache, diarrhea, dyspepsia
allergic reactions - SJS
hemolysis, agranulocytosis, thrombocytopenia
mesalamine products to target different sites
asacol: released in terminal ileum
pentasa: released in small bowel, can open the capsules (increased diarrhea)
aminosalicylate forms
oral, enema, suppository
aminosalicylate 5ASA dosing possibility
can give any of the qid 5ASA tablets or capsules as a single daily dose
can you give 5ASA in a patient with an ASA allergy
yes
how long to assess clinical response to aminosaliccylates
4-8 weeks
lowest dose that can be used for aminosalicylate
2g/day
if fail 4.8g of one agent what do you do
dont switch to diff 5ASA, pick a different agent
aminosalicylate efficacy in UC
remission in some
decrease relapse rate in half the patients
most effective in more distal disease
aminosalicylate efficacy in CD
benefit is in the colon not ileal disease
corticosteroid suppository used for
proctitis
corticosteroid enema used for
left sided (sigmoid/rectum) disease for uncontrolled UC
when would you use topical corticosteroids
mild-mod left sided UC not controlled with 5ASA
budesonide MMX in mild=mod right side colonic and ileal disease
when do you use systemic corticosteroids
treatment for mod-severe UC and CD
good for flares
onset of systemic corticosteroids
few days to a week
if fail 1 week have to use big guns
reevaluate in 2 weeks
is there long term use of systemic corticosteroids
yes but many problems with long term use, not good to prevent relapse long term
patinets just cant get off them
efficacy of azathioprine and 6mercaptopurine
induce and maintain remission
heals fistulas
allows elimination of steroids
onset of azathioprine/6mercaptopurine
1 month for improvement
3 to see if actually working
how does azathioprine and 6mercaptopurine work
induces t cell apoptosis
describe the break down of sulfasalazine
the diazo bond is cleaved by bacteria into sulfapyridine (responsible for the AE) which is rapidly absorbed into circulation form the colon
aminosalicylates are not the same as
cox 2 inhibitors
why is it so important to ensure adherance to aminosalicylates
once you go beyond this the next drugs have big time toxicity so want to keep on 5ASA as long as possible
problem with buesonide MMX
maintaining remission wiht it alone
what is thiopurine methyltransferase
major regulator of 6 TG concentration
____ TPMT activity leads to preferential metabolism of 6 TG (increase efficacy and toxicity)`
low
how is thiopurine methyltransferase enzyme activity determined
genetically
polymorphism
exmplain azathioprine breakdown
breaks down into 6mercaptopurine then into thioinsinic acid
TPMT breaks that into 6methylmercaptopurine or it breaks down into thioguanine metabolite
explain TPMT testing
becoming the standard of care
17 mutant allelles but only tests for the most common 3
problem with TPMT testing
patients with a recent blood transfusion willhave other peoples RBC so may seem like they have normal TPMT when its actually low
have to wait 3 months for the RBC to die???
can you rely on the TPMT testing to predict who will have severe myelosuppression from azathiopirine
no
STILL HAVE TO DO BLOOD TESTS REGULARLY to ensure myelosuppresssion doesnt happen
very important drug interaction to remember
azathiopurine and allopurinol
SE of AZA 6MP
neutropenia atypical infection pancreatitis - first 6 weeks watch for ab or back pain and vomiting skin rash small increase in maignancies
do you need PJP prophylaxis when on AZA
not unless also on high dose steroids
CBC monitoring for aza
weekly for first month then every 2 weeks for month 2 and 3 then every month
what do you ask someone getting a drug that needs blood work
when theyre getting blood work done not if
methotrexate is used fr
CD similar results to aza somewhat faster onset but still need a month trial
not used in UC except if refractory to aza
methotrexate contraindicated in
pregnant women
AE of methotrexate
neutropenia
atypicla infections
liver dysfunction
pneumonitis
dosing with immunomodulator methotrexate
no set dosing
cyclosporine use
severe active UC refusing surgery or have bad surgical risks limited to 6 months use
to brudge patients to aza
if a patient fails on methylprednisolone and refuses surgery we use
anti TNF
how does infliximab work
antibody that binds to tumor necrosis factor and induces t cell apoptosis
infliximab used for
severe active or fistulizing CD
active UC
best data for remission in fistulizing crohns
dosing of infliximab and time for response
3 doses at 0,2,6 weeks
see a response in the first week
how long do people stay on infliximab
data for up to 1 year but some people on it indefinitely although we are still learning how long its efficacy and safety lasts
what to do if not responding to induction doses of infliximab
no benefit in continuing into maintenance therapy with the same agent
what to do if not responding to the first anti tnf agent
evidence of benefit in trying another one though response is lower than in the anti TNF naive
infliximab SE
nausea
URT infections
GI pain
infections - impairment of IS, TB reactivation, too rapid closure of fistulas
allergic reactions
infusion related reactions - headache, flushing, dizzy
infliximab long term issues
infections - tuberculosis malignancies lupus like syndrome demyelinatin - optic neuritis, MS pancytopenia hepatic lymphomas in young people - hepatosplenic T cell lymphomas cases were fatal leukemias new onset psoriasis
impact of antibody formation to murine component of infliximab
loss of response
need to increase dose or frequency
ways to prevent infliximab antibody formation
intermittent use increase risk of antibodies so use continuously i guess
dont start on infliximab unless patient agrees to go on aza
pretreat with steroids if just starting treatment
anti TNF questions for the pahrmacist
have they previously been exposed to antiTNF
are pretreatment steroids required
mantoux test or chest xray (to test for TB), baseline LFT and hepatitis viral studies been performed
antidiarrheals for supportive therapy
loperamide and codiene - cna use prior to sports to decrease ileostomy drainage
stop temporarily whrn CD deteriorates quickly
never use in severe disease as increases risk of toxic megacolon
cholestyramine for bile salt diarrhea
drugs for inducing remssion in UC
aminosalicylates with mild-mod corticosteroids cyclosporine antiTNF vedolizumab
drugs for maintaining remission in UC
aminosalicylates with mild-mod disease
AZA,6MP, maybe MTX
anti TNP
vedolizumab
monitoring UC therapy
scoring systems of disease activity
rectal bleeding and diarrhea, frequency of stools/day
anemia, low albumin, increased ESR, fever, ab pain - serious
fever new ab pain - see doctor
adherence very important - esp with 5ASA
drugs for inducing remission in crohns
corticosteroids
anti TNFs
drugs for maintaining remission in crohns
aminosalicylate? budesonide? aza, 6MP, methotrextae antiTNF metronidazole, ciprofloxacin sometimes in ileal or colonic never use cyclosporin
monitoring crohns therapy
heterogenous features
heal fistula, decrease in diarrhea and ab pain
weight, hemoglobin, endoscopic features
frequency of needing support therapy - ex loperamide
frequency of missing school or work
whats the main treatment for mild - mod UC
5ASA
difference between crohns and ulcerative colitis
crohns: occurs in the colon and lower SI commonly but can affect entire GI tract, can comprise multiple separate areas of inflammation, can form fissures
UC: affects only sigmoid colon and rectum, continuous patch of inflammation, damages inner lining of intestinal wall
