Gastrointestinal Part 2

Question 1

ssxs of IBD?

Answer 1

abd pn
vomiting
diarrhea
hematochezia
wt loss

Question 2

differences in location, thickness affected, inflammation, ulcerations, mucous membrane, lymphocytic infiltration, fistulas and strictures in UC vs Crohn’s?

Answer 2

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

Question 3

what 4 ways can you tx IBD?

Answer 3

corticosteroids/glucocorticoids
aminosalicylates
immunosuppressants/biologics
antibiotics

Question 4

corticosteroid used to tx IBD?

Answer 4

prednisone/prednisolone

Question 5

MOA of prednisone/prednisolone?

Answer 5

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

Question 6

prednisone/prednisolone is used how?

Answer 6

used to tx acute flares or as salvage therapy

Question 7

glucocorticoid used to tx IBD?

Answer 7

budesonide

Question 8

MOA of budesonide? metabolism?

Answer 8

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

Question 9

2 aminosalicylates used to tx IBD?

Answer 9

mesalamine

sulfasalazine

Question 10

mesalamine MOA?

Answer 10

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

Question 11

4 examples of mesalamine?

Answer 11

asacol
lialda
pentasa
rowasa

Question 12

which mesalamine category drug has action from the stomach through the LI?

Answer 12

pentasa

Question 13

which mesalamine category drug has action from mid-SI through the LI?

Answer 13

asacol

Question 14

which drug has anti-IBD activity in the LI only?

Answer 14

sulfasalazine (azo compound)

Question 15

MOA of sulfasalazine? ADRs? odd SE?

Answer 15

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

Question 16

3 categories of immunosuppressants?

Answer 16

folic acid derivatives
purine analongs
pyrimidine analogs

Question 17

azathioprine MOA?

Answer 17

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

Question 18

pre-drug of 6-mercaptopurine?

Answer 18

azathioprine

Question 19

ADRs of azathioprine? major interaction w/what?

Answer 19

leukopenia, thrombocytopenia, hepatotxicity, infxn, malignancy, malaise, n/v
major interaction w/EtOH

Question 20

monoclonal ab we use to tx IBD?

Answer 20

tumor necrosis factor (immunosuppressant)

Question 21

MOA of anti-tumor necrosis factor?

Answer 21

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

Question 22

relative C/Is for using TNF-a to treat IBD?

Answer 22

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)

Question 23

ADRs of anti-TNF-a?

Answer 23

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

Question 24

2 anti-TNF-a drug we use to tx IBD?

Answer 24

infliximab

adalimumab

Question 25

MOA of infliximab? interaction w/?

Answer 25

chimeric IgGk that binds to both free and membrane bound TNF-a
major interaction w/DMSO
can raise ANA titer, lead to ab development

Question 26

MOA of adalimumab?

Answer 26

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

Question 27

Why are the differences between the different immunosuppressants important if they all work the same?

Answer 27

will produce less abs against the meds and pts SEs may increase or decrease depending upon which one they’re using

Question 28

two classes of anti-nausea/emesis drugs?

Answer 28

serotonins antagonists

dopamine antagonists/prokinetics

Question 29

serotonin antagonist we talk about?

Answer 29

ondansetron

Question 30

MOA of ondansetron? onset? duration?

Answer 30

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

Question 31

ADRs of ondansetron?

Answer 31

CV (QT prolongation), h/a, fatigue/malaise, diarrhea, transient transaminitis

Question 32

if serotonin antagonists prevent/treat nausea what would you expect SSRIs to cause?

Answer 32

nausea!!

Question 33

2 dopamine antagonists we talk about?

Answer 33

promethazine

metoclopramide

Question 34

MOA of promethazine?

Answer 34

blocks postsynaptic mesolimbic dopaminergic receptors in the brain, exhibits a strong a-adrenergic blocking effect and depresses the release of hypothalamic and hypophyseal hormones

Question 35

ADRs of promethazine?

Answer 35

arrhythmia, hypotension, dopamine-suppresion “extrapyramidal” effects, endocrine effects

Question 36

MOA of metoclopramide?

Answer 36

antagonizes dopamine receptors and at high doses blocks serotonin receptors in chemoreceptor trigger zone of the CNS (antiemetic)

Question 37

ADRs of metoclopramide?

Answer 37

relatively few at low doses but at higher doses increased risk for dopamine-suppression extrapyramidal effects

Question 38

metoclopramide has effects on which receptors?

Answer 38

serotonin and 5HT3 receptors