Pharm for IBD Flashcards
Drug types for IBD
5-ASA Corticosteroids immunosuppressants Anti-TNF alpha antibodies alpha4-integrin monoclonal antibody antibiotics (not FDA approved for IBD)
5-Aminosalicylic Acid (mesalamine, 5-ASA)
Delayed or extended release:
Apriso, Asacol, Lialda, Pentasa
Prodrug formulations:
Sulfasalazine, balsalazide, olsalazine
Rectal formulations:
Rowasa, Canasa
Corticosteroids
Prednisone
* Budesonide
Hydrocortisone
Immunosuppressants
- Azathioprine
- Mercaptopurine (6-MP)
Methotrexate (MTX)
Cyclosporine
Anti-TNFα Antibody
- Infliximab (Remicade)
Adalimumab (Humira)
Certolizumab pegol (Cimzia)
α4-Integrin Monoclonal Antibody
Natalizumab (Tysabri)
Antibiotics (not FDA approved for IBD)
Metronidazole (Flagyl)
Ciprofloxacin (Cipro)
Drug List: IBS
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
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
THe answer is LOCAL chem mediators (5ASA)
More about other answer choices:
muscarinic choinergic receptors- antispasmodics
purine nucleotide synth- mercaptopurine, etc.
step-up approach to IBD
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
for flares we use
oral corticosteroids
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
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
what agents are Associated with insomnia and behavioral changes
corticosteroids
method of action of sulfa drugs?
folic acid inhibitors
pt with sulfa drug and UC.
Which one of the following drug therapies is best? 6-mercaptopurine Hydrocortisone enema Mesalamine Sulfasalazine
likely mesalamine after ruling out sulfasalazine
6-mercaptopurine would be further down the road if this is ineffective
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?
Budesonide
azothiaprine, infliximab, mercaptopurine– monitor for what?
immunosuppression
infliximab– rule out infectious diseases
mesalamine can cause what kind of side effects?
potentially some GI issues
corticosteroids MOA
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
After dose reduction of budesonide, the patient experiences fever, abdominal pain, and 5-6 bloody bowel movements per day.
What is this?
flare in a steroid-dependent patient
what should we do for the steroid-dependent patient?
Initiate azathioprine and attempt to taper the budesonide
or
Initiate infliximab and attempt to taper the budesonide
Anti-TNFα Antibodies MOA
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
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
TB!
allopurinol- watch out for 6MP
diabetes- corticosteroids- watch glucose leveles
Progressive multifocal leukoencephalopathy- mataluzimab
psychiatric disorders- steroids
Purine Analogs MOA
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
Which of the following is not a dose-dependent side effect of sulfasalazine?
Dyspepsia Headache Malaise Nausea Skin rash
all of these are potential side effects, but the rash can’t be helped with changing the drug dose
Crohn’s disease, mesalamine and bedesonide no longer working. What should we do?
corticosteroids short term
TNF-alpha, 6MP are some other choices, or in combination
Irritable Bowel Syndrome (IBS)
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
IBS Goals of Therapy
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
Chloride Channel Activator
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)
5-HT4 Partial Agonist
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
5-HT3 Antagonist
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
Antispasmodics
Available agents: dicyclomine, hyoscyamine
MOA: inhibit muscarinic cholinergic receptors
ADRs: anticholinergic side effects – dry mouth, visual disturbances, urinary retention, constipation
- Not routinely used
