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Summer pharm 4 > IBD > Flashcards

IBD Flashcards

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1
Q

What is comprised in IBD

A

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

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2
Q

What causes IBD

A

Combo of infectious, genetic, environmental, and immunologic

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3
Q

Pharm Tx for IBD involves

A

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

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4
Q

What are Sx of UC

A 
rectal bleeding 
abd ttp 
Continuous distribution 
rectal involvement 
crypt abscesses
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5
Q

What are Sx of Crohn’s

A 
Fever, malaise 
rectal bleeding 
abd pain 
abd mass 
fistulas
aphthous ulcers 
discontinuous distribution 
ileal involvement 
strictures 
transmural 
granulomas 
linear clefts 
cobblestoning
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6
Q

Drugs that are less effective but with fewer ADE

A

Budesonide
Topical steroids
Antibiotics
5-aminosalicylates

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7
Q

Agents that are most effective but with a lot of ADE

A

Natalizumab
Cyclosporine
TNF antagonists
IV corticosteroids

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8
Q

What happens to aminosalicylates in the body

A

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

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9
Q

What constitutes mild (low risk) Crohn’s

A 
No/Mild Sx 
Nl/mils elevation of CRP
Diagnosed 30+ 
Limited distribution 
No prior resections 
No strictures
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10
Q

How do you treat mild, low risk crohn’s

A

Budesonide to induce remission

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11
Q

What are the Aminosalicylates (5-ASA)

A

Azo compounds: Sulfasalazine, Olsalazine, Balsalazide

Mesalamine

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12
Q

What is the significance of Azo compounds

A

The structure reduces absorption from small intestine

In the terminal ileum and colon, bacteria cleave the azo bond and release active 5-ASA

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13
Q

What are the formulations of Mesalamine

A

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

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14
Q

What is the site of action of the IBD drugs

A

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

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15
Q

What is the PK of IBD drugs

A

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

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16
Q

What is the MOA of 5-ASA

A

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

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17
Q

How does 5-ASA work in UC and Crohn’s

A

UC: Induce and maintain remission

Crohn’s: efficacy unproven, used mainly for mild-mod involving colon or distal ileum

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18
Q

What is first lint Tx for mild-mod UC

A

5-ASA!!!

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19
Q

Efficacy of 5-ASA depends on

A

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
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20
Q

What are ADE of Sulfasalazine

A 
nausea 
vomiting 
HA 
rash 
hepatotoxicity, nephritis 
-monitor folate, CBC, LFT, SrCr, BUN 
*Has more ADE than others bc it is a fast acetylator
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21
Q

What are ADE of Olsalazine

A

secretory diarrhea

-monitor oligospermia (reverses on drug d/c)

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22
Q

What are ADE of Mesalamine

A

N/V
Headache
High dose: Interstitial nephritis

23
Q

How do glucocorticoids work in IBD

A

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
Q

What is the MC steroid used in IBD

A

Prednisone and prednisolone

Oral, QD

25
Q

What are other steroids used in IBD

A

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
Q

What is Entocort

A

Controlled release budesonide released thru distal ileum and colon
PO

27
Q

What are steroids used for

A

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
Q

ADE of corticosteroids are

A 
hyperglycemia 
dyslipidemia 
osteoporosis 
HTN 
acne 
edema 
infection 
myopathy 
psychosis 
-Monitor BP, fasting lipids, glucose, vit. D, bone density
29
Q

What are the pruine analogs

A

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

30
Q

What ahppens to 6-MP in the body

A

Biotransformed via competing catabolic enzymes; Xanthine oxidase, Thiopurine methyltransferase

31
Q

What should you not give Xanthine oxidase with

A

Allopurinol (XO inhibitor)- so you get double XO inhibition

Increases active 6-thioguanine nucleotides= severe leukopenia

32
Q

What is the PK of purine analogs

A

Half life <2 hours

Takes 17 weeks before therapeutic benefit or oral purine analogs

33
Q

What are clinical uses of purine analogs

A

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
Q

What are ADE of purine analogs

A

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
Q

Can purine analogs be used in pregnancy

A

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

36
Q

How can Abx influence the course of IBD

A

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
Q

How does Methotrexate work

A

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
Q

What disorders does methotrexate treat

A

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

39
Q

Clinically, methotrexate is used to

A

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

40
Q

ADE of high dose methotrexate are

A

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
Q

Other ADE of methotrexate are

A

if w/ psoriasis: hepatic damage

hepatic accumulation and toxicity if w/ renal insufficiency

42
Q

How do anti-TNF agents work in IBD

A

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

43
Q

Wha are the biologic actions of TNF

A

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

44
Q

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

A 
Infliximab 
Adalimumab 
Certolizumab 
Natalizumab 
Vedolizumab 
(golimumab, Inflixi, adalim, and Vedo in UC)
45
Q

How do anti-TNF work

A

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
Q

What are the clinical uses of anti-TNF

A

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
Q

What are ADE of anti-TNF

A

*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
Q

What does concomitant use of anti-TNF and immunomodulators do

A

increase risk of lymphoma

49
Q

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

A

Using immunomodulators like 6-MP or methotrexate

50
Q

What are Integrins

A

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
Q

What is Natalizumab

A

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

52
Q

What is Natalizumab used for

A

Mod-severe crohn’s who fail Tx

CArefully restricted program

53
Q

ADE of Natalizumab are

A

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

54
Q

What is Vedolizumab

A

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

Summer pharm 4 (14 decks)

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