IBD Flashcards Preview

Summer pharm 4 > IBD > Flashcards

Flashcards in IBD Deck (54):
1

What is comprised in IBD

UC: mucosal inflammatory condition confined to rectum and colon
Crohn's: transmural inflammation of GI tract, mouth to anus

2

What causes IBD

Combo of infectious, genetic, environmental, and immunologic

3

Pharm Tx for IBD involves

anti-inflammatories
1. Aminosalicylates (Sulfasalazine, Mesalamine)
2. Corticosteroids (prednisone, budesonide)
(Also Tx with abx, immunosuppressives, biologics, and anti-integrins)

4

What are Sx of UC

rectal bleeding
abd ttp
Continuous distribution
rectal involvement
crypt abscesses

5

What are Sx of Crohn's

Fever, malaise
rectal bleeding
abd pain
abd mass
fistulas
aphthous ulcers
discontinuous distribution
ileal involvement
strictures
transmural
granulomas
linear clefts
cobblestoning

6

Drugs that are less effective but with fewer ADE

Budesonide
Topical steroids
Antibiotics
5-aminosalicylates

7

Agents that are most effective but with a lot of ADE

Natalizumab
Cyclosporine
TNF antagonists
IV corticosteroids

8

What happens to aminosalicylates in the body

Sulfasalazine: converted to mesalamine in the colon
Asacol: Release is delayed until terminal ileum and cecum, then released as a bolus in right colon

9

What constitutes mild (low risk) Crohn's

No/Mild Sx
Nl/mils elevation of CRP
Diagnosed 30+
Limited distribution
No prior resections
No strictures

10

How do you treat mild, low risk crohn's

Budesonide to induce remission

11

What are the Aminosalicylates (5-ASA)

Azo compounds: Sulfasalazine, Olsalazine, Balsalazide
Mesalamine

12

What is the significance of Azo compounds

The structure reduces absorption from small intestine
In the terminal ileum and colon, bacteria cleave the azo bond and release active 5-ASA

13

What are the formulations of Mesalamine

Pentasa: timed release microgranules throughout small intestine
Asacol/Apriso: Coating dissolves at pH 6-7; distal ileum and proximal colon
Lialda: Dissolves in pH of colon. Slow release throughout colon
Rowasa: enema
Canasa: Suppository

14

What is the site of action of the IBD drugs

Jejunum: Pentasa
Ileum: Asacol, Lialda
Proximal colon: Sulfasalazine, Balsalazide
Rectum: Rowasa, Canasa

15

What is the PK of IBD drugs

Absorption of 5-ASA from colon is very low
Absorbed 5-ASA undergoes N-Acetylation in the gut and liver and is converted to a metabolite that is not anti-inflammatory
That metabolite is excreted by kidneys

16

What is the MOA of 5-ASA

Modulates inflammatory mediators derived from COX and LOX pathways
Interferes with production of inflammatory cytokines (NF-Kb)
Inhibit cell fxn of NK cells, lymphocytes, macrophages
Scavenge reactive oxygen metabolites

17

How does 5-ASA work in UC and Crohn's

UC: Induce and maintain remission
Crohn's: efficacy unproven, used mainly for mild-mod involving colon or distal ileum

18

What is first lint Tx for mild-mod UC

5-ASA!!!

19

Efficacy of 5-ASA depends on

achieving high drug concentration at site of active disease
-Rowasa and Canasa good for dz confined to rectum or distal colon
-azo compounds and mesalamine for dz in proximal colon
-pentasa, asacol, lialda for dz involving small bowel

20

What are ADE of Sulfasalazine

nausea
vomiting
HA
rash
hepatotoxicity, nephritis
-monitor folate, CBC, LFT, SrCr, BUN
*Has more ADE than others bc it is a fast acetylator

21

What are ADE of Olsalazine

secretory diarrhea
-monitor oligospermia (reverses on drug d/c)

22

What are ADE of Mesalamine

N/V
Headache
High dose: Interstitial nephritis

23

How do glucocorticoids work in IBD

Inhibit inflammatory cytokines (TNF, IL1) and chemokines (IL8)
Reduce expression of inflammatory cell adhesion
Inhibit gene transcription of NO synthase, phospholipase A2, COX2, and NF-Kb

24

What is the MC steroid used in IBD

Prednisone and prednisolone
Oral, QD

25

What are other steroids used in IBD

Hydrocortisone: maximize colon effects, minimize systemic absorption. Topical Tx in rectum and sigmoid
Budesonide: prednisolone synthetic analog. rapid first pass hepatic metabolism (low oral bioavailability) (entocort, uceris- PO forms in US)

26

What is Entocort

Controlled release budesonide released thru distal ileum and colon
PO

27

What are steroids used for

mod-severe active IBD- a flare! NOT to maintain remission (need 5-ASA or biologics for that)
Higher doses are NOT more effective, just more ADE
After response (1-2 weeks), slowly taper
If very ill, can give IV
If involving rectum or sigmoid colon, rectally administered preferred

28

ADE of corticosteroids are

hyperglycemia
dyslipidemia
osteoporosis
HTN
acne
edema
infection
myopathy
psychosis
-Monitor BP, fasting lipids, glucose, vit. D, bone density

29

What are the pruine analogs

Azathioprine (more bioavailable!)- converted to 6-MP
6-Mercaptopurine
-They are anti-metabolites with immunosuppressive properties

30

What ahppens to 6-MP in the body

Biotransformed via competing catabolic enzymes; Xanthine oxidase, Thiopurine methyltransferase

31

What should you not give Xanthine oxidase with

Allopurinol (XO inhibitor)- so you get double XO inhibition
Increases active 6-thioguanine nucleotides= severe leukopenia

32

What is the PK of purine analogs

Half life <2 hours
Takes 17 weeks before therapeutic benefit or oral purine analogs

33

What are clinical uses of purine analogs

Induce and maintain remission of UC and Crohn's after 3-6 months of Tx
Allow reduction and elimination of steroids in most pts

34

What are ADE of purine analogs

N/V
bone marrow depression (anemia, low plt, wbc)
hepatic toxicity (monitor CBC, LFT)
hypersensitivity to azathioprine (fever, rash, pancreatitis, diarrhea, hepatitis
Increased risk of lymphoma

35

Can purine analogs be used in pregnancy

CAN cross placenta but many women used during pregnancy and teratogenicity is small

36

How can Abx influence the course of IBD

Decrease bacteria and fungi in gut/lumen
Alter composition of mictobiota
Decrease bacterial tissue invasion and Tc microabscess
Decrease bacterial translocation and systemic dissemination

37

How does Methotrexate work

Inhibit dihydrofolate reductase enzyme (needed to make thymidine and purines)
Can interfere with inflammatory actions of IL
Can stimulate increased release of adenosine, and apoptosis/death of active T lymphocytes

38

What disorders does methotrexate treat

Crohn's
RA
Cancer
-oral (50% bioavailable), subQ, IM (appx 100% bioavailable)

39

Clinically, methotrexate is used to

induce and maintain remission in crohn's (1x wk subQ)- if effective after 8-12 weeks, can reduce dose

40

ADE of high dose methotrexate are

bone marrow depression
megaloblastic anemia
alopecia
mucositis
-reduce the dose! and reduce risk of ADE with FOLATE*
-permanent peripheral neuropathy if used for prolonged periods

41

Other ADE of methotrexate are

if w/ psoriasis: hepatic damage
hepatic accumulation and toxicity if w/ renal insufficiency

42

How do anti-TNF agents work in IBD

Dysregulate helper T cella type 1 (Th1) response and regulatory T cells

43

Wha are the biologic actions of TNF

release proinflammtory cytokines from macrophages
Activate and proliferate T cells
Up regulate adhesion molecules (leukocyte migration)
Stimulate hepatic acute phase reactants

44

What anti-TNF (TNF MAB's) are approved for use in Crohn's

Infliximab
Adalimumab
Certolizumab
Natalizumab
Vedolizumab
(golimumab, Inflixi, adalim, and Vedo in UC)

45

How do anti-TNF work

Bind soluble and membrane bound TNF
prevent cytokine from binding to receptors
Cause reverse signaling that suppresses cytokine release
-Inflix/Adalim/Golim: Fc portion promotes Ab mediated apoptosis. Also complement activation, and cytotoxicity to T lymphocytes and macrophages
Certo: No Fc portion= no apoptosis

46

What are the clinical uses of anti-TNF

Acute and chornic mod-severe Crohn's not responsive to Tx
1/3 of pts eventually lose response (may be 2/2 development of Abs to TNF Ab (Abs to the Abs; ATA)

47

What are ADE of anti-TNF

*Infection! 2/2 supprssion of T helper cells (Th1)- sepsis, TB, invasive fungal, reactivation of Hep B or latent TB
-Increased risk if also on steroids
Less serious: URI (sinusitis, bronchitis, PNA), cellulitis
*Delayed serum sickness-like Rxn: myalgia, arthralgia, jaw tightness, fever, rash, urticaria, edema
+ANA and anti-ds DNA
Lupus like syndrome (goes away w/ drug d/c)
Hepatic reactions, demyelinating d/o, hematologic d/o, new or worse CHF, psoriatic skin rash, lymphoma

48

What does concomitant use of anti-TNF and immunomodulators do

increase risk of lymphoma

49

What makes the likelihood of developing antibodies to antibodies while using anti-TNF

Using immunomodulators like 6-MP or methotrexate

50

What are Integrins

Adhesion molecules on the surface of leukocytes
interact with selectins, adhesion molecules on vascular endothelium
Allow leukocytes to adhere to vascular endothelium and move thru vessels into tissue

51

What is Natalizumab

Anti-integrin; IgG4 MAB that blocks integrins and prevents migration into surrounding tissues

52

What is Natalizumab used for

Mod-severe crohn's who fail Tx
CArefully restricted program

53

ADE of Natalizumab are

Acute infusion reaction
Opportunistic infections
-Monitor brain MRI, mental status, PMI

54

What is Vedolizumab

Similar to natalizumab but:
Selectively blocks the gut (NOT brain)
Prevents JC virus (more selective)
Can be used in crohn's ad UC