Pharm for IBD

Question 1

Drug types for IBD

Answer 1

5-ASA
Corticosteroids
immunosuppressants
Anti-TNF alpha antibodies
alpha4-integrin monoclonal antibody
antibiotics (not FDA approved for IBD)

Question 2

5-Aminosalicylic Acid (mesalamine, 5-ASA)

Answer 2

Delayed or extended release:
Apriso, Asacol, Lialda, Pentasa

Prodrug formulations:
Sulfasalazine, balsalazide, olsalazine

Rectal formulations:
Rowasa, Canasa

Question 3

Corticosteroids

Answer 3

Prednisone
* Budesonide
Hydrocortisone

Question 4

Immunosuppressants

Answer 4

• Azathioprine
• Mercaptopurine (6-MP)
  Methotrexate (MTX)
  Cyclosporine

Question 5

Anti-TNFα Antibody

Answer 5

• Infliximab (Remicade)
  Adalimumab (Humira)
  Certolizumab pegol (Cimzia)

Question 6

α4-Integrin Monoclonal Antibody

Answer 6

Natalizumab (Tysabri)

Question 7

Antibiotics (not FDA approved for IBD)

Answer 7

Metronidazole (Flagyl)

Ciprofloxacin (Cipro)

Question 8

Drug List: IBS

Answer 8

Laxatives

• Lubiprostone
• Bulk-forming laxatives (psyllium, bran)

Antidiarrheal Agents

• Loperamide (Imodium)
• Diphenoxylate (Lomotil)

5-HT3 Antagonist
- Alosetron

Antispasmodic Agents (anticholinergics)

• • Dicyclomine (Bentyl)
• • Hyoscyamine sulfate

Antidepressants
- Amitriptyline

Question 9

For the initial treatment of mild-to-moderate UC, an agent with which of the following mechanisms of action would be most appropriate? Inhibition of:

Inflammatory cytokine production
Local chemical mediators of inflammation 
Muscarinic cholinergic receptors 
Purine nucleotide synthesis
TNFα-mediated inflammatory responses

Answer 9

THe answer is LOCAL chem mediators (5ASA)

More about other answer choices:
muscarinic choinergic receptors- antispasmodics

purine nucleotide synth- mercaptopurine, etc.

Question 10

step-up approach to IBD

Answer 10

mild- budesonide, topical corticosteroids, abx, 5-ASAs

moderate- TNF antagonists, oral corticosteroids, methotrexate, azathioprine/ 6-mercaptopurine

severe: surgery (curative in UC but not so much in crohn’s), natalizumab, cyclosporine, TNF antagonists, IV corticosteroids

Question 11

for flares we use

Answer 11

oral corticosteroids

Question 12

Aminosalicylates are:

A. Associated with insomnia and behavioral changes
B. Available only in oral formulations
C. Generally used first for induction and maintenance of remission in mild-to-moderate UC
D. Proven effective for induction and maintenance of remission in mild-to-moderate CD

Answer 12

C. generally used first for induction and maintenance of remission to mild-to- moderate UC

not proven to be effective in crohn’s but still used

Question 13

what agents are Associated with insomnia and behavioral changes

Answer 13

corticosteroids

Question 14

method of action of sulfa drugs?

Answer 14

folic acid inhibitors

Question 15

pt with sulfa drug and UC.

Which one of the following drug therapies is best?
6-mercaptopurine
Hydrocortisone enema
Mesalamine
Sulfasalazine

Answer 15

likely mesalamine after ruling out sulfasalazine

6-mercaptopurine would be further down the road if this is ineffective

Question 16

Since initiation of a new drug, the patient has required additional blood pressure, serum glucose, and weight monitoring. What was most likely begun one year ago?

Answer 16

Budesonide

Question 17

azothiaprine, infliximab, mercaptopurine– monitor for what?

Answer 17

immunosuppression

infliximab– rule out infectious diseases

Question 18

mesalamine can cause what kind of side effects?

Answer 18

potentially some GI issues

Question 19

corticosteroids MOA

Answer 19

Available agents: prednisone, budesonide, hydrocortisone

MOA:
Inhibits production of inflammatory cytokines (TNF-α, IL-1) and chemokines (IL-8)
Reduces expression of inflammatory cell adhesion molecules
Inhibits gene transcription of nitric oxide synthase, phospholipase A2, cyclooxygenase-2, and NF-κβ

Question 20

After dose reduction of budesonide, the patient experiences fever, abdominal pain, and 5-6 bloody bowel movements per day.

What is this?

Answer 20

flare in a steroid-dependent patient

Question 21

what should we do for the steroid-dependent patient?

Answer 21

Initiate azathioprine and attempt to taper the budesonide

or

Initiate infliximab and attempt to taper the budesonide

Question 22

Anti-TNFα Antibodies MOA

Answer 22

Available agents: infliximab, adalimumab, certolizumab
MOA: bind soluble and membrane bound TNF with high affinity
Prevents receptor binding
Causes reverse signaling and suppresses cytokine release

Question 23

The decision is made to begin infliximab. Which of the following must be ruled out before initiating therapy? what are the dangers of the other classes?

Allopurinol
Diabetes
Progressive multifocal leukoencephalopathy  
Psychiatric disorders
Tuberculosis

Answer 23

TB!

allopurinol- watch out for 6MP
diabetes- corticosteroids- watch glucose leveles
Progressive multifocal leukoencephalopathy- mataluzimab
psychiatric disorders- steroids

Question 24

Purine Analogs MOA

Answer 24

Available agents: azathioprine, 6-mercaptopurine
MOA: azathioprine  6-MP  active metabolites which suppress nucleotide synthesis, B-cell and T-cell function, immunoglobulin production, and IL-2 secretion

Question 25

Which of the following is not a dose-dependent side effect of sulfasalazine? ``` Dyspepsia Headache Malaise Nausea Skin rash ```

Answer 25

all of these are potential side effects, but the rash can't be helped with changing the drug dose

Question 26

Crohn's disease, mesalamine and bedesonide no longer working. What should we do?

Answer 26

corticosteroids short term TNF-alpha, 6MP are some other choices, or in combination

Question 27

Irritable Bowel Syndrome (IBS)

Answer 27

Occurs ~15% of U.S. population, 2:1 female to male Idiopathic disorder Abdominal discomfort with alterations in bowel habits Pathophysiology: Enteric nervous system contains a significant number of serotonin receptors which have become an area of focused research

Question 28

IBS Goals of Therapy

Answer 28

Relieve abdominal pain and improve bowel function First step = dietary change Chronic abdominal pain Low doses of tricyclic antidepressants - No effect on mood but may alter central processing of visceral information - Anticholinergic effects – GI motility, reduce stool frequency

Question 29

Chloride Channel Activator

Answer 29

Lubiprostone MOA: stimulates type 2 chloride channels, stimulates intestinal fluid secretion, decreases colonic transit time Therapeutic Use: Women with constipation predominant IBS ADRs: nausea (delayed gastric emptying)

Question 30

5-HT4 Partial Agonist

Answer 30

Agent: tegaserod MOA: activates 5-HT4, increases GI motility, and decreases visceral sensations Therapeutic Use: Women with severe constipation predominant IBS Improves symptoms within 1st week of therapy ADRs: diarrhea Increased risk of ischemic events

Question 31

5-HT3 Antagonist

Answer 31

Agent: alosetron MOA: inhibits afferent receptors reducing unpleasant sensations including bloating, nausea, and pain Inhibits colonic motility, increases transit time Therapeutic Use: Women with severe diarrhea predominant IBS ADRs: constipation

Question 32

Antispasmodics

Answer 32

Available agents: dicyclomine, hyoscyamine MOA: inhibit muscarinic cholinergic receptors ADRs: anticholinergic side effects – dry mouth, visual disturbances, urinary retention, constipation - Not routinely used