IBD Tx

Question 1

What drug classes are used in IBD

Answer 1

5 aminosalicylic acid preparations
corticosteroids
immunosuppressants
Anti TNF alpha Ab
alpha4 integrin monoclonal Ab
Antibiotics

Question 2

What are the drug classes used in IBS

Answer 2

laxatives
anti diarrheal agents
prokinetic agent
serotonin antagonist
antiaspasmodic agents (Anticholinergics)
antidepressents

Question 3

UC affects what areas of GI

Answer 3

affects rectum and colon, mucosal and submucosal layers

superficial inflammation

Question 4

complications UC

Answer 4

hemorrhoids, anal fissures, perirectal abscesses
toxic megacolon
colorectal carcinoma

Question 5

what is toxic megacolon

Answer 5

segmental or total colonic distention of greater than 6 cm with acute colitis and signs of systemic toxicity

Question 6

describe ulcers in CD

Answer 6

deep and elongated with nodular submucosal thickening

Question 7

UC or CD has higher risk for fistula formation

Answer 7

CD

Question 8

complications of CD

Answer 8

small bowel structures, fistulas, bleeding,nutritional deficiencies and extra-intestinal manifestations

Question 9

What drugs are amiosalicylates used for IBD

Answer 9

sulfasalazine, olsalazine, balsalazide, various forms mesalamine

Question 10

MOA aminosalicylates

Answer 10

uncertain. maybe modulates inflammatory medioators derived from cyclooxygenase and lipooxygenase

Question 11

describe metabolism sulfasalazine, balsalazide and olsalazine

Answer 11

decrease absorption of parent drug in small intestine

high [ ] of active drug in terminal ileum or colon

Question 12

describe the delayed or extendened release forms of msealamine

Answer 12

coated in special resins, pH sensitive film or ethylcellulose that release drug slowsly thorugh GI tract or only in terminal ileum and colon

Question 13

what are the rectal formulations of mesalamine

Answer 13

rowasa and canasa

Question 14

therapeutic use for aminosaliclyates

Answer 14

1st line for mild to moderate UC

Question 15

effectiveness of aminosalicylates is determined how

Answer 15

by drug reaching site of active disease
suppositories useful in UC or CD rectum or distal colon
if proximal colon use axo and mesalmine formulations

Question 16

adverse effects aminosalicylates

Answer 16

dose related: nausea, GI upset, HA, arthralgias, myalgias, bone marrow suppression, malaise
nephrotoxicity
lupus like syndrome, pancreatitis, hepatotoxicity

Question 17

what are the glucocorticoids used for IBD

Answer 17

prednisone, budesonide, hydrocortisone

Question 18

MOA glucocorticoids

Answer 18

inhibit production inflammatory cytokines TNFa and IL-1 and IL-8
reduce expression inflammatory cell adhesion molecules
inhibit gene transcription NO synthase, PLA2, COX-2, NFkB

Question 19

therapeutic use glucocorticoids

Answer 19

mod- severe IBD
higher dose treat active disease
once responding, taper dose
hydrocortisone enemas used to maximize colonic tissue effects and minimize absorption

Question 20

What is budesonide

Answer 20

potent synthetic analog of prednisolone with high affinity for glucocorticoid receptor
rapid first pass metabolism, low oral bioavailability and controlled release formulation that releases drug in distal ileum and colon

Question 21

adverse effects glucocorticoids

Answer 21

insomnia, behavioral changes, acute peptic ulcers
fluid and electrolyte abnormalities, metabolic changes, HTN, hyperglycemia, increased susceptibility to infections, osteoporosis, myopathy, behavioral disturbances, cataracts, growth arrest

Question 22

what are the purine analogs

Answer 22

azathioprine, 6 mercaptopurine

Question 23

MOA purine analogs

Answer 23

inhibits purine NT synthesis
azathioprine is converted to 6 MP which coverts to active metabolites that suppress inosinic acid synthesis, B cell and T cell function, Ig production and IL-2 secretion

Question 24

PK of purine analogs

Answer 24

delay of 17 weeks before onset therapeutic benefit from oral azathioprine of 6 MP in IBD

Question 25

therapeutic use purine analogs

Answer 25

induction and maintenance of remission of UC and CD for patients who need long term glucocorticoid therapy to control active disease, purine analogs, allow dose reduction or elimination of steroids in the majority, d/t delay onset limited short time but effective long term

Question 26

adverse effects purine analogs

Answer 26

dose related nausea vomiting bone marrow depression and hepatic toxicity also HS: fever rash, pancreatitis, diarrhea, hepatitis increase risk lymphoma with long term therapy

Question 27

drug interactions with purine analogs

Answer 27

allopurinol with 6MP | allopurinol inhbits the enzyme that metabolizes 6MP to inactive compound increasing toxic effects

Question 28

MOA methotrexate MTX

Answer 28

inhibits dihydrofolate reductase affecting lymphocyte and macrophage function may stimulate release of adenosine, an endogenous anti-inflammatory autocoid may also stimulate apoptosis and death of activated T lymphocytes

Question 29

therapeutic use of MTX

Answer 29

induction and maintenance of remission in patients with CD | Efficacy in UC uncertain

Question 30

adverse effects MTX

Answer 30

high doses may cause bone marrow depression, megaloblastic anemia, alopecia and mucositis

Question 31

what should you give with MTX

Answer 31

folate supplementation to decrease risk of adverse effects

Question 32

MOA cyclosporine

Answer 32

an inhibitor of calcineurin; cyclosporine is a potent inhibitor of cell-mediated immune responses - inhibits IL2 production form T helper cells - decreases recruitment of cytotoxic T cells and blocks other cytokines, including IL3 and 4, IFalpha and TNGa

Question 33

therapeutic use cyclosporine

Answer 33

IV infusion used to Tx severe UC that is unresponsive to IV glucocorticoids; may save patient from colectomy, but carries significant toxicity

Question 34

TNF levels in IBD

Answer 34

increased because key pro-inflammatory cytokine and mediator of intestinal inflammation

Question 35

Available TNFa Ab agents in IBD

Answer 35

``` infliximab, adalimumab are Ab of IgG1 subclass certolizumab- recombinant Ab that contains a Fab fragment conjugated to polyethylene glycol (PEG) ```

Question 36

what monoclonal Ab are fully humanized

Answer 36

adalimumab

Question 37

MOA TNFa Ab

Answer 37

all 3 Ab, bind soluble membrane bound TNFa with high affinity, preventing the cytokine from binding its receptors suppreses cytokine release lyses macrophages and T cells through C' fixation and Ab dep cytotoxicity

Question 38

therapeutic use of TNFa

Answer 38

acute and chronic Tx of mod-severe CD in patients who have inadequate response to conventional therapies

Question 39

median time to clinical response TNFa

Answer 39

2 weeks

Question 40

adverse effects TNFa

Answer 40

serious infections, Ab to Ab, delayed serum sickness like reaction hepatic failure, lupus like syndrome, demyelinating disorders, hematologic reactions and new or worsening CHF psoriatic skin rashes- resulting after drug discontinuation, lymphoma

Question 41

what serious infections can occur with TNFa

Answer 41

bacterial sepsis, TB, invasive fungal infections

Question 42

before starting on TNFa therapy what must you check for

Answer 42

TB infection because TB therapy needs to be initiated first

Question 43

What infecitons are more common with TNFa

Answer 43

URI(sinusitis, bronchitis, pneumonia) and cellulitis, risk of serious infection increases when taking concomitant glucocorticoids

Question 44

describe delayed serum sickness like reaction from TNFa

Answer 44

1-2 weeks post antiTNFa therapy | myalgia, arthralgia, jaw tightness, fever, rash, edema

Question 45

What are integrins

Answer 45

family of adhesion molecules on leukocytes that interact with selectins allowing leukocytes to enter vascular endothelium and into tissue

Question 46

what are the available anti-integrin agents

Answer 46

natalizumab, humanized IgG2 monoclonal Ab

Question 47

MOA natalizumab

Answer 47

prevent integrin binding to vascular adhesion molecules inhibiting subsequent migration into surround tissues

Question 48

therapeutic use of natalizumab

Answer 48

subset of patients with mod- severe CD

Question 49

why was natalizumab withdrawn in general.

Answer 49

lead to progressive multifocal leukoencephalopathy

Question 50

what is natalizumab still approved for

Answer 50

restricted use in patients with mod-severe CD who failed other Tx

Question 51

adverse effects natalizumab

Answer 51

acute infusion reactions and a small risk of opportunistic infections