IBS and IBD Pharm Flashcards
What are the treatment agents for Ulcerative Colitis?
5-ASA
Corticosteroids
TNF Inhibitors
Alpha-4 integrin inhibitors
5-ASA
“sala”
Corticosteroids
“one”
TNF inhibitors
“mab”
What is the ONE alpha-4 integrin inhibitor?
Vedolizumab
What are the treatments for Crohn disease?
- IL-12/23 inhibitors
- Corticosteroids
- TNF inhibitors again
- alpha 4 integrin inhibitors
What is the one IL-12/23 inhibitor?
Ustekinumab
TNF?
mab again
the TWO Alpha-4 integrin inhibitors for Crohn?
Natalizumab
Vedolizumab
What is Sulfasalazine?
sulfapyridine and aspirin (5-ASA)
mesalamine?
just aspirin
Olsalazine
2 molecules of aspirin
Balsalazide
inert carrie and aspirin
How far are oral aspirin things distributed?
may be the entire GI tract
Rectal enemas… how far do they reach?
may reach the splenic flexure
-do not frequently concentrate int he rectum
Where do rectal suppositories concentrate?
-they reach the upper rectum
15-20 cm beyond the anal verge
What is 5-ASA’s Mechansim of Action?
- inhibition of PG and LT production via arachidonic acid pathway
- Reduction in PMN and macrophage chemotaxis
What are some side effects of 5-ASA products?
dizziness/headache/fatigue
In what patients are all 5-ASA compounds contraindicated in?
ASA- allergic patients
What patients have sulfalazine contraindications?
sulfonamide-allergic patients
What are some indications of 5ASA agent?
mild to moderate active UC and maintenance of Remission of UC
What is only used for maintenance therapy?
Olsalazine
What is only used for the treatment of active disease?
Balsalazide
What is also indicated for jevenile-arthritis
Sulfasalazine
What are the TNG-alpha inhibitors?
the “mab”s
MOA for TNF alpha inhibitors?
- neutralizes membrane-associated and soluble human TNG alpha mediate pro inflammatory cell signaling
- inhibits expression of pro-inflammatory genes
What are some side effects of TNG alpha inhibitors?
Infections
-to TB test pre-therapy
What are the indications for TNF alpha inhibitors?
treatment of active and maintenance
Which 2 tnf inhibitors can tread both UC and CD?
Adalimumab and Infliximab
Which TNF inhibitor only works for UC?
Golimumab
Which TNG inhibitor only works for CD?
the one that starts with C
-Certolizumab
What is the dosing for each of the TNF inhibitors?
- Adalimumab: SQ (subcutaneous) every other wek
- Infliximab: IV infusion every 8 weeks
- Golimumab: SQ every 4 weeks
- Certolizumab: SQ every 4 weeks
What are the alpha 4 integrin inhibitors?
Natalizumab: recombinant humanized IgG4 monoclonal antibody
-Vedolizumab: humanized IgG1 monoclonal antibody
MOA of alpha 4 integrin inhibitors?
limits integrin’s associated cell adhesion, transendothelial migration, and immune cell activation with in inflamed tissue
Side effects of Alpha 4 integrin inhibitors?
PML (this is a big deal… progressive multifocal leukoencephalopathy)
- 3 risk factors for PML: treatment for >2 years
- prior immunosuppressant treatment
- anti-JC virus antibodies
Indications for Alpha 4 integrin inhibitors
- moderat to severe treatment resisntantt CD and maintenance therapy to prevent relapse (Natalizumab)
- Moderate to severe treatment resisntant CD and UC (vedolizumab) and maintenance therapy to prevent relapse
What is the dosing of alpha 4 integrin inhibitors?
Natalizumab: IV infusion every 4 weeks
Vedolizumab: IV infusion every 8 weeks
What is the one IL-12/23 inihibitor?
ustekinumab
MOA of IL-12/23 inhibitors?
bind to a specific subunit of IL-12/23 receptor located on surface of T cells and NK cells
-thereby inhibiting signal transduction-related activities and production of pro-inflammatory Th1 and Th17 cells
Side effect of IL-12/23 inhibitors
-Infections, TB testing pre-therapy recommended
Indications for IL-12/23 inhibitors
-Moderate to severe treatment resistant CD (both active disease and maintenance)
Dosing of IL-12/23
Ustekinumab
- Administered IV as a single infusion (induction)
- SQ every 8 weeks (for maintenance)
Glucocorticoids
Prednisone/methylprenisolone/dexamethasone/etc.
Mechanism of Glucocorticoids
binding to specific cytoplasmic receptors induces a response by modifying transcription and, ultimately protein synthesis, to achieve the steroid’s intended action, including:
- inhibition of leukocyte infiltration at site of inflammation
- interference in the function of mediators of inflammatory response
- suppression of humoral immune responses
Adverse effects revisited
- increase glucose , bp, and lipid profile
- GI distress
- fluid retention/edema/swelling of face and extremities
Indications for Steroids
Acute and/or severe UC and CD uncontrolled by other conventional medications
Dosing of steroids
use the lowest dose for shortest duration possible
What does IBS stand for?
Irritable bowel syndrome
What is IBS?
a complex of symptoms
- individual symptoms w/ limited accuracy in diagnosis
- abdominal pain
- diarrhea or constipation
What are antimuscarinic agents used for?
abdominal pain
What are the antimuscarinic agents?
- hyoscyamine
- dicyclomine
- clidinium
- chlordiazepoxide
What are the Bulk-Forming and laxative Agents?
- psyllium
- methylcellulose
- polyethylene-glycol (PEG)
- lactulose
- Polycarbophil
- Magnesium
Anti-Diarrheals
Loperamide
Diphenoxylate
Opiod agonists/antagonists
eluxadoline
Serotonin (5HT3) antagonists
Alosetron
Guanylate cyclase-C Agonists
Linaclotide
Selective chloride (C2 channel activators)
Lubiprostone
What are Antimuscarinics used for
for abd. pain/spasms
MOA of antimuscarinics
Competitively-inhibit autonomic, post-ganglionic cholinergic receptors (multiple sites
-results in decreased GI motility and spasms
Side effects of antimuscarinics
easy: just think everything anticholinergic
- dry mouth
- urinary retention
- constipation
- drowsiness
- mental confusion
- blurred vision
What 3 classes of drugs are used for diarrhea?
- Anti-Diarrheals: loperamide, diphenoxylate (bismuth)
- Opioid Agonists/antoagonists: eluxadoline
- Serotonin Antagonists: Alosetron
MOA of Loperamide?
- interferes with peristalsis by a direct action on circular and longitudinal muscles of the intestinal wall, slowing motility
- also may directly inhibit fluid and electrolyte secretion and.or increase water absorption
- chemically related to opioids without opioid actions
Side effects of Loperamide?
-constipation, dizziness, drowsiness, and urinary retention (anticholinergic)
MOA of Diphenoxylate?
-exerts effect locally and centrally on GI smooth muscle cells; inhibits GI motility and slows excess GI propulsion
Side effects of Diphenoxylate?
-constipation, dizziness, drowsiness and urinary retention
MOA of Alosetron?
- selectively blocks GI-based 5HT3 receptors
- antagonism at 5HT3 receptors in GI tract modulate regulation of visceral pain, colonic transit and GI secretions
Side effects of Alosetron?
- GI complaints: constipation, dyspepsia, GERD and N/V
- **Ischemic Colitis*
Indication for Alosetron?
Women with chronic, sever IBS-D no responsive to other conventional therapies
-so, it’s pretty intense
MOA of Eluxadoline
- agonist at opioid mu and kappa receptors in GI tract (slows peristalsis/delays digestion)
- antagonist at delta opioid receptors in GI tract… decreases stomach, pancreas and biliary tract secretions
Side effects of Eluxadoline
- GI related
- Hepatic.pancreatic toxicity
- CNS-related
What 3 drug classes are used for constipation?
- Bulk-forming and laxative agents (don’t worry about them)
- Guanylate cyclase-C agonists: Linaclotide
- Selective Chloride (C2) channel activators: Lubiprostone
MOA of Linaclotide
- binds to Guanylate cyclase-C on luminal surface of intestinal epithelium (agonist)
- increases cGMP
- stimulates secretion of chloride/bicarb into intestinal lumen via activation of CFTR ion channel
- results in increased intestinal fluid and accelerated transit
Side effects of Linaclotide
- Diarrhea
- other GI-related: abd pain/dyspepsia/N/V/Flatulence
Indications for Linaclotide
IBS-C
- Chronic Idiopathic Constipation (CIC)
- not supported <17 years of age
MOA of Lubiprostone
- Activates apecific CIC-2 chloride channels in luminal cells of intestinal epithelium
- produces a chloride-rich intestinal fluid secretion without altering serum electrolyte concentrations
- a PGE-1 derivative
Side effects of Lubiprostone
-Nausea, dyspepsia, dizziness
Indications for Lubiprostone
IBS-C (women)… not men
-Chronic idopathic constipation (CIC) adults
