Gastrointestinal Part 2 Flashcards
ssxs of IBD?
abd pn vomiting diarrhea hematochezia wt loss
differences in location, thickness affected, inflammation, ulcerations, mucous membrane, lymphocytic infiltration, fistulas and strictures in UC vs Crohn’s?
Crohn’s: proximal, skip lesions, rectum often spared, intestinal wall thickened (cobblestones), inflammation in all layers, deep ulcerations, always lymphocytic inflammation, fistulas and strictures common
UC: rectum always affected, distal effects, thickness is normal, inflammation in superficial layers, superficial ulcerations, rare to see lymphocytic infiltration or fistulas and strictures are suggestive of neoplasm
what 4 ways can you tx IBD?
corticosteroids/glucocorticoids
aminosalicylates
immunosuppressants/biologics
antibiotics
corticosteroid used to tx IBD?
prednisone/prednisolone
MOA of prednisone/prednisolone?
modulates protein synth leading to reduced migration of PMN leukocytes and fibroblasts, reverses capillary permeability and lysosomal stabilization at the cellular level to prevent or control inflammation, immunosuppression
prednisone/prednisolone is used how?
used to tx acute flares or as salvage therapy
glucocorticoid used to tx IBD?
budesonide
MOA of budesonide? metabolism?
MOA: modulates protein synth leading to reduced migration of PMN leukocytes and fibroblasts, reverses capillary permeability and lysosomal stabilization at the cellular level to prevent or control inflammation, immunosuppression
metabolism: undergoes rapid and extensive 1st pass metabolism to minimal activity by-products
2 aminosalicylates used to tx IBD?
mesalamine
sulfasalazine
mesalamine MOA?
modulates local chemical mediators of the inflammatory response, particularly leukotrienes and acts as a free radical scavenger or an inhibitor of tumor necrosis factor. Most of activity is typical despite oral dosage forms
4 examples of mesalamine?
asacol
lialda
pentasa
rowasa
which mesalamine category drug has action from the stomach through the LI?
pentasa
which mesalamine category drug has action from mid-SI through the LI?
asacol
which drug has anti-IBD activity in the LI only?
sulfasalazine (azo compound)
MOA of sulfasalazine? ADRs? odd SE?
MOA: prodrug is mesalamine, the Azo (N=N) bond is cleaved by colonic bacteria and is then active
ADRs: dose dependent= nausea, anorexia, folate deficiency, h/a, alopeica
dose independent= male infertility, rash, hemolytic anemia, hepatitis, pancreatitis, agranulocytosis
SE: causes urine, tears and sweat to develop a yellow/orange tinge
3 categories of immunosuppressants?
folic acid derivatives
purine analongs
pyrimidine analogs
azathioprine MOA?
inhibits purine synthesis and DNA replication resulting in an anti-proliferative effect and induction of apoptosis of T-cells, pro-drug which is converted in the body to its active form 6-mercaptopurine
pre-drug of 6-mercaptopurine?
azathioprine
ADRs of azathioprine? major interaction w/what?
leukopenia, thrombocytopenia, hepatotxicity, infxn, malignancy, malaise, n/v
major interaction w/EtOH
monoclonal ab we use to tx IBD?
tumor necrosis factor (immunosuppressant)
MOA of anti-tumor necrosis factor?
inhibit TNF-a which is responsible for the induction of proinflammatory cytokines, enhancement of leukocyte migration, activation of neutrophils and eosinophils and the induction of acute phase reactants and tissue degrading enzymes
relative C/Is for using TNF-a to treat IBD?
active HBV infxn multiple sclerosis, optic neuritis active serious infections chronic or recurrent infections current neoplasia history of TB or (+) PPD CHF (class III or IV)
ADRs of anti-TNF-a?
infusion reactions/anaphylaxis, infection (TB and HBV re-activation), h/a, transaminitis, n/v
premedication w/antihistamines, acetaminophen and/or corticosteroids may be considered to prevent and manage infusion-related reactions
2 anti-TNF-a drug we use to tx IBD?
infliximab
adalimumab
MOA of infliximab? interaction w/?
chimeric IgGk that binds to both free and membrane bound TNF-a
major interaction w/DMSO
can raise ANA titer, lead to ab development
MOA of adalimumab?
human mAb (IgG1k) against TNF-a initially give 160 mg as four 40 mg injections on day 1 or two 40 mg injections over 2 days) then 80 mg 2 wks later w/maintenance dose every other week beginning day 29 of 40 mg VERY EXPENSIVE
Why are the differences between the different immunosuppressants important if they all work the same?
will produce less abs against the meds and pts SEs may increase or decrease depending upon which one they’re using
two classes of anti-nausea/emesis drugs?
serotonins antagonists
dopamine antagonists/prokinetics
serotonin antagonist we talk about?
ondansetron
MOA of ondansetron? onset? duration?
MOA: selectively antagonists serotonin at 5-HT3 receptors both peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zone
onset 30 mins
duration 3-6 hrs
ADRs of ondansetron?
CV (QT prolongation), h/a, fatigue/malaise, diarrhea, transient transaminitis
if serotonin antagonists prevent/treat nausea what would you expect SSRIs to cause?
nausea!!
2 dopamine antagonists we talk about?
promethazine
metoclopramide
MOA of promethazine?
blocks postsynaptic mesolimbic dopaminergic receptors in the brain, exhibits a strong a-adrenergic blocking effect and depresses the release of hypothalamic and hypophyseal hormones
ADRs of promethazine?
arrhythmia, hypotension, dopamine-suppresion “extrapyramidal” effects, endocrine effects
MOA of metoclopramide?
antagonizes dopamine receptors and at high doses blocks serotonin receptors in chemoreceptor trigger zone of the CNS (antiemetic)
ADRs of metoclopramide?
relatively few at low doses but at higher doses increased risk for dopamine-suppression extrapyramidal effects
metoclopramide has effects on which receptors?
serotonin and 5HT3 receptors
