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126 Cards in this Set
- Front
- Back
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intestine shit
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ulcerative colitis classification by extent (2)
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distal
extensive |
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what does distal UC mean
3 examples |
limited to descending colon (proctitis, proctosigmoiditis, left sided colitis)
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fulminant UC
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Sudden, rapid progression from mild to severe
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look over disease classifications
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5 goals of therapy in IBD
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Relieve symptoms (induce remission)
Maintain remission Resolve/prevent complications Minimize toxicity of medications Improve patient’s quality of life |
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nutritional support for IBD (2)
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-certain foods worsen sx- get rid of them
-parenteral nutrition in severe disease to rest bowels |
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supplement support for IBD (3)
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-VSL #3 (probiotic)
-vitamins -iron (IV if can't take oral)- i guess for bleeding |
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meds to be cautious/avoid using in IBD (4)
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-use antidiarrheals, antispasmodics, and opioid analgesics very cautiously in IBD patients and avoid in severe disease- can precipitate toxic megacolon
-avoid NSAIDs |
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step-up approach for IBD (4 drugs)
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ACIM (ace em!)
-Aminosalicylates (or abx- only used first line in special situations) -->corticosteroids- get off this step asap-->immunosuppressants-->monoclonal ab |
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goal of step up therapy
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Start with least toxic agents first
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top down therapy- what is it
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starting from monoclonal ab- then adding others as needed
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steroid dependent definition
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Flare-ups when steroid dose is decreased or discontinued
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steroid refractory definition
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no response to max dose of steroids
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suppository site of activity
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poop chute (rectum)
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foam site of activity
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to sigmoid colon (bendy part right after rectum)
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extensive UC- definition
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-Extends into transverse and/or
ascending colon |
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pancolitis definition
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extensive UC that extends into the
ascending colon |
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enema site of activity
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to splenic flexure (entire left side)
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covers distal and proximal colon (and rectum)
3 drugs |
sulfasalazine
balsalazide olsalazine |
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mesalamine (asacol, lialda, apriso)- site of activity
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all the way to proximal, distal colon and includes terminal ileum
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covers entire intestinal tract
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pentasa (mesalamine)
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Suppositories would be best for...
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proctitis
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Enemas would be best for...
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left sided disease
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aminosalicylates use in UC (2)
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Mainstay of therapy to induce and maintain remission
pouchitis (rectal) |
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aminosalicylates use in CD (1 use, and one comment about that use)
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First line to induce (not maintain) remission in CD (use in
maintenance unclear) use in CD is common, but it is off-label |
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pouchitis definition
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inflammation of the ileal pouch (an artificial rectum surgically created out of ileal gut tissue in patients who have undergone a colectomy
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aminosalicylates- how long do you use it for? why?
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protective against colorectal cancer so patients are usually kept on these agents indefinitely if no serious adverse effects
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mesalamine aka...
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5-ASA
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mesalamine oral formulation property
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enteric coating or carrier molecule? so it will pass the SI
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mesalamine CI
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patients with
aspirin/salicylate allergy |
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mesalamine MoA
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local anti-inflammatory effect; may inhibit PG synth
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onset of action of mesalamine
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-sx usually under control within 3 wks or less
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sulfasalazine- what is it?
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Prototype aminosalicylate with antimicrobial AND anti-inflammatory effects
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sulfasalazine- structure, how this structure contributes to how the drug works
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contains sulfonamide (sulfapyridine) bound to 5-ASA
In the lower intestines, the molecule is cleaved and 5-ASA is released |
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sulfasalazine- CI and efficacy
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sulfa group was stupid, just causes more ADR and no extra efficacy
CI in pt with sulfa allergies |
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general dosing rules for sulfasalazine (2)
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Adjust based on response and
tolerance start low and go slow due to GI tox |
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dose dependent sulfasalazine AE (6)
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N/V/D, headache, alopecia,
anorexia, arthralgia, thrombocytopenia |
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idiosyncratic AE of sulfasalazine (7)
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hypersensitivity/rash,
agranulocytosis, hemolytic anemia, hepatitis pancreatitis lupuslike syndrome Male infertility (reversible) |
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sulfasalazine- major AE that causes setback for health (and how to fix it)
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Impaired folic acid absorption (i thought it inhibits DHFR...); supplement
with 1 mg/day folic acid PO |
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different oral forms of mesalamine (5)
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asacol
asacol HD lialda apriso pentasa |
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which mesalamine form is once daily (2)
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lialda
apriso |
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which mesalamine brand names are rectal?
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rowasa
canasa |
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2 mesalamine DERIVATIVES
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balsalazide
olsalazine |
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mesalamine dosing in maintenance phase
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cut in half from doses taken during induction of remission
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aminosalicylate side effects- general trend (severity and duration)
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Common, but usually mild and disappear as treatment continues
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aminosalicylate side fx (5)
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headache, GI (nausea, abdominal pain,
dyspepsia), rash |
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aminosalicylate side fx specific to rectal formulations (3)
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rectal formulations may cause rectal
irritation, flatulence, abdominal fullness |
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major side effect of olsalazine
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Olsalazine causes severe watery diarrhea in up to 1/3 of patients
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rare side fx of aminosalicylates (4)
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pancreatitis, arthralgia, cutaneous reactions, interstitial nephritis (monitor serum creatinine periodically)
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need to monitor what labs in aminosalicylates (2)
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monitor serum creatinine periodically due to rare cases of interstitial nephritis
cbc in old ppl |
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efficacy of aminosalicylates- is one better than the others?
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nope
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sulfasalazine pro (1) and cons (2)
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inexpensive,
contraindicated in patients with sulfa allergy, lots of adverse effects |
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mesalamine pros (4) and con (1)
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more favorable adverse effect
profile, can use in patients with sulfa allergy, better tolerated than sulfasalazine, rectal available |
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mesalamine routes- use separately or together?
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Oral and rectal formulations can be used together.
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pentasa frequency of dosing
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4x daily
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which mesalamine formulations are given 3x a day (2)
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asacol
asacol HD |
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2 abx available for IBD (certain situations)
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flagyl (metronidazole)
ciprofloxacin |
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metronidazole is primarily used in CD or UC
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CD
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metronidazole first line uses (3)
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fistulas
pouchitis prevent recurrence of CD after resection |
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metronidazole second line use
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in active CD if satisfactory control is not gained with aminosalicylates
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metronidazole use in UC
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Sometimes used in UC, but no evidence of efficacy
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metronidazole dosing frequency
duration of treatment in pouchitis vs others |
TID
pouchitis more temp- 1-2 weeks others will be months |
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route of admin for metronidazole (2 diff cases)
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po mostly
but if severe fistulizing disease you give IV first cuz i guess they can't take oral, then oral |
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long term therapy with metronidazole- watch out for what side effect?
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peripheral neuropathy- idk why
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ciprofloxacin usage (2)
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Alternative to metronidazole (same uses) or may consider combining with metronidazole
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cipro routes and frequency of dosing
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BID
PO, unless severe fistulizing (then IV) |
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corticosteroids- UC or CD?
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both
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corticosteroid use (2)
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Induction of remission in patients with moderate to severe IBD (CD or UC)
maybe pouchitis (both rectal/oral) |
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corticosteroid- what do we NOT use it for (2)
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not for immunosuppressant effect (not high enough dose)
not useful for maintenance of remission |
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MoA of corticosteroids in IBD (2)
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Work quickly to reduce inflammation by interfering with steps in the inflammation process
Decrease diarrhea by enhancing water and sodium absorption |
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cautions to take with corticosteroids (3- including avoiding use in what)
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May mask signs of peritonitis, a precursor to
toxic megacolon Suppress cortisol production so must be tapered before discontinuation Avoid use in fistulizing disease |
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corticosteroids- AE (11)
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Hyperglycemia, hypertension, osteoporosis,
acne, fluid retention, electrolyte disturbances, myopathies/muscle wasting, increased appetite/weight gain, psychosis, reduced resistance to infection really shit tolerability |
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2 options for oral corticosteroids
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budesonide
prednisone |
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which corticosteroid has extensive first pass metabolism and limited systemic absorption
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budesonide
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benefit (supposed) of budesonide
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better tolerability profile due to less bioavailability
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usage specific to budesonide
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Used in CD involving the ileocecal area/ascending colon (acts
locally) |
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efficacy of budesonide
cost |
not as effective as other steroids and more
expensive (cost is several hundred dollars/month) |
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rectal corticosteroid
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hydrocortisone (remember it's topical)
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can you give oral + rectal for corticosteroids?
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yeah
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rectal hydrocortisone- when to give
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qHS- i guess easier to keep shit in when you're sleeping
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IV forms of corticosteroids (2)
when would you use IV? |
hydrocortisone
methylprednisone use if pt is hospitalized |
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Immunosuppressants usage in IBD (3)
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Steroid-sparing agents (i.e., to minimize the dose of steroids required)
Maintenance therapy Pouchitis and fistulas |
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immunosuppressants are not supposed to be used for what?
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Not for acute disease because onset of action is 3-6 months
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immunosuppressants for IBD (3)
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azathioprine
methotrexate cyclosporine |
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azathioprine: class, drug structure property
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thiopurine
prodrug (converted to 6-MP) |
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TPMT role (2)
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converts AZA to 6-MP via thiopurine
methyltransferase (TPMT) enzyme; TPMT enzyme also metabolizes 6-MP to some degree |
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AZA vs. 6-MP usage
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AZA is used more often than 6-MP because of its
more favorable therapeutic index |
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AZA/6-MP dosing rules (3) - route, frequency, etc
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Start low and go slow to minimize adverse effects
oral QD |
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ADR for AZA (9)
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N/V/D, anorexia, hepatitis, pancreatitis***(big one), arthralgia,
malaise/fever, rash, bone marrow suppression (esp if TPMT deficient), non- Hodgkin’s lymphoma (low risk in IBD dosing) |
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usage of methotrexate (2)
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-2nd line after AZA/6-MP in steroid-dependent CD (to..induce remission?)
-2nd line after AZA/6-MP to maintain CD remission note that methotrexate is used only in CD |
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monitoring for AZA- which lab is important?
how frequent to monitor? (3) |
monitor CBC weekly for 4 weeks
then every 2-4 weeks for 8 weeks then every 1-2 months thereafter |
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TPMT testing for AZA users- yay or nay?
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FDA recommends TPMT testing before beginning therapy with thiopurines
but it's rarely done because of cost and the fact that you can minimize toxicity anyway by starting low and going slow |
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methotrexate dosing (route, frequency and difference between inducing remission and maintenance doses for CD)
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SQ weekly
remission dose is lower |
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8 AE for methotrexate
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N/V/D, anorexia, pneumonitis, stomatitis, elevated liver function tests, fibrosis, cirrhosis, pancytopenia/thrombocytopenia
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methotrexate in pregnancy
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teratogenicity
(pregnancy category X) obviously- stop cell growth = stop baby cell growth |
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methotrexate monitoring (2) when to do these labs?
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Liver enzymes periodically; liver biopsy after 5 g cumulative dose over course of therapy has been reached
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3 uses for monoclonal antibodies
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- Moderate to severe active IBD unresponsive to conventional therapy
- Maintenance once active disease is under control -Pouchitis (only infliximab) and fistulas (infliximab, limited evidence for adalimumab and certolizumab) |
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cyclosporine usages (3) EXAM
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-used as last resort (rescue therapy) to avoid proctocolectomy in pt with UC (if can't or won't accept surgery)
-can also try if no response to high dose steroids after a week (refractory pt) -or as a bridge to other immunosuppressants -also used in CD pt with fistulas unresponsive to abx, aza/6-mp and methotrexate |
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why is cyclosporine a good bridging abx?
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has a more rapid onset than AZA, 6-MP and methotrexate
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cyclosporine used in which IBD
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both- but UC it's used as last resort and in CD it's used for unresponsive fistulas
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cyclosporine dosing notes (3)
route/frequency dosing adjustments? |
continuous IV infusion
need to change to AZA or 6-MP asap to maintain remission need to adjust in renal impaired - i don't htink it has to do with metabolism...but maybe renal toxicity? |
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8 ADRs of cyclosporine
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Hypertension, paresthesias, tremors, headache,
electrolyte disturbances, nephrotoxicity, bone marrow suppression, seizures in people with low cholesterol levels (decrease dose) |
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monoclonal Ab MoA (2 different drugs that have different MoAs)
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TNF-a inhibitors- they bind to TNF-A and neutralize its biologic activity (infliximab, adalimumab, certolizumab)
Adhesion molecule (alpha-integrin) inhibitor – blocks adhesion and migration of inflammatory white blood cells from the blood vessels into gut tissues |
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TNF-a- what is it/more prominent in what disease
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proinflammatory cytokines implicated in IBDappears to play a more significant role in CD
pathogenesis than in UC |
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the monoclonal Ab that is an alpha integrin inhibitor (not TNF-a)
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natalizumab
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Infliximab general dosing rules (route/duration)
what do you do if patient responds but then stops responding? |
IV infusion over 2 hrs
increase to 10 mg/kg |
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adalimumab route of admin
dosing regimen (don't need to know exact dose) |
SQ self administer
taper dose (cut in half) every 2 weeks, then continue at lower dose QoW |
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4 monoclonal Ab choices
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Certolizumab
adalimumab natalizumab infliximab |
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Certolizumab- dosing frequency (after introduction) and route
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SQ (given by pro)
q4weeks |
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Natalizumab dosing route/duration/freq
when to stop |
IV infusion over 1 hour
q4weeks If patient does not respond by week 12, discontinue |
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when would you use natalizumab?
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Use if TNF-a inhibitors are ineffective or if
patients cannot tolerate TNF- inhibitors |
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monoclonal ab that is highly restricted and why
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natalizumab
because it has a really bad side effect (Progressive multifocal leukoencephalopathy- PML) |
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10 monoclonal Ab adverse effects
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n/v/d
ab pain dyspepsia HA htn fever arthralgia back pain upper RTI (and all included possibilities there like sinusitis, bronchitis, etc) UTI infusion related hypersensitivity |
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All patients considered for treatment with TNF-a inhibitors must receive...
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a tuberculin skin test to rule out tuberculosis- WHY?? immunosuppressant effect i think...
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possible cause for infusion reaction + loss of drug response for monoclonal ab
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Antibodies to monoclonal antibodies may develop, resulting in infusion reactions and loss of response to drug
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TNF-a inhibitor black box warnings (4)
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heart failure, increased liver enzymes and/or hepatotoxicity, lymphoma, serious/opportunistic infections like TB
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monoclonal ab- only one approved for UC
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Only infliximab is approved for UC; all 4 are approved for CD
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first and last choice monoclonal ab
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Infliximab probably first choice if monoclonal antibody
needed; natalizumab probably last choice |
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cost and insurance coverage of monoclonal abs
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All are very expensive (~$2500+ per infusion/injection)
If covered by insurance, most require documentation that at least 2 of the other classes (aminosalicylates, corticosteroids, and immunosuppressants have been tried and failed) |
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something other than antibody reaction that can cause loss of response of INFLIXIMAB (not others i think)
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smoking- not enzyme related because it's a protein...maybe oxidants dmg the proteins
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Natalizumab drug combos- 2 things to keep in mind
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cannot be given with immunosuppressants EXAM
corticosteroids should be tapered when starting natalizumab other monoclonal abs are fine with corticosteroids and shit |
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5 of IBD drugs safe in pregnancy
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Aminosalicylates, corticosteroids, AZA/6-MP, cyclosporine, TNF-a inhibitors
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Metronidazole pregnancy/boob feed usage (2)
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some concern with use in first
trimester use controversial in breastfeeding |
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ciprofloxacin pregnancy/breast feed use
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conflicting information (also in
breastfeeding, but know it's not one of the preferred quinolones) |
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IBD drug absolutely contraindicated in pregnancy and breastfeeding
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Methotrexate - CATEGORY X YAY
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