Lecture 21 - AntiDiarrheal Drugs, IBS, and IBD

Question 1

Absorbents

Answer 1

Absorb excess water to form a gel-like mass; some agents can bind to microbial toxins.

• Bulk Forming Agents
• Hydrate Aluminum Silicate-Kaolin and Attapulgite (NOT ON EXAM)

Question 2

Bulk Forming Agents (Dietary Fiber)

Answer 2

Bind excess water to yield partially formed stool.
Do not decrease the bulk of fecal material

Question 3

Bismuth Subsalicylate

Answer 3

Properties: Anti-secretory, anti-inflammatory, antimicrobial that absorbs excess water and relieves nausea and abdominal cramps.

Prevent/treat: Traveler’s Diarrhea, Episodic diarrhea, and acute gastroenteritis.

Adverse Effects:
- Dark stool
- Salicylate: Systemic effects, NOT for aspirin allergic, NOT for children (Reye’s Synd, use Bismuth citrate)

Question 4

Paregoric

Answer 4

Opium extract (w/ morphine)

Inhibit peristalsis through circular smooth muscle constriction and longitudinal muscle relaxation.

Not used often anymore, replaced by loperamide.

Question 5

Loperamide

Answer 5

Opioid analog (50x more potent than morphine as antidiarrheal) that decreases peristaltic movements.

No CNS effects (low abuse potential) at therapeutic doses due to poor BBB crossing potential.

Therapeutic use:
- No improvement in 48h = discontinue
- NOT FOR age <2
- RISK OF TOXIC MEGACOLON (Not for inflammatory bowel disease)

Question 6

Toxic Megacolon (Symptom)

Answer 6

During inflammatory bowel syndrome, wall of bowel is inflamed and weakened.

Shape of bowel maintained through contraction of circular muscles ONLY at this point. Loperamide inhibits muscles, causing pressure to outcompete constriction and lead to bowel distend.

Question 7

Hyoscyamine, Dicyclomine (Other: atropine, homatropine, belladonna extracts, glycopyrrolate, propantheline, isopropamide)

Answer 7

Anticholinergic (antispasmodic) drugs.

For intestinal cramping associated with irritable bowel syndrome.

Side effects/ toxicity include sedation, dry mouth, dry hot skin, constipation, urine retention, loss of visual accommodation.

NOTE: Dicyclomine is most likely to be abused.

Question 8

Citrate and salicylate, Pepto-Bismol

Answer 8

Colloidal bismuth compounds

Absorbs excess water

Bismuth can provide some microbial toxins/ directly toxic to some pathogens.

Salicylate: inhibit prostaglandin synthesis (antisecretory and antiinflammatory)

Non specific diarrhea (“travelers’)

Darkens stool

Salicylate - systemic effects

Bismuth subsalicylate: NOT FOR THOSE ALLERGIC TO ASPIRIN (Reye’s syndrome, use Bismuth citrate)

Question 9

Sulfasalazine

Answer 9

For inflammatory bowel disease.

Sulfapyridine (antimicrobial) and salicylate (anti-inflammatory) together.

Side effects: allergic reactions, hemolytic anemia, blood dyscrasias (similar to sulfonamides)

Question 10

Mesalamine

Answer 10

Sulfasalazine that can be given orally or by retention enema for the treatment of ulcerative colitis.

Question 11

Irritable Bowel Syndrome (IBS-D and IBS-C)

Answer 11

Vaguely defined motility disorder characterized by concomitant:
- Abdominal pain: Bloating, distention, cramps
- Changes in bowel habits: Constipation (IBS-C) and/or Diarrhea (IBS-D)

IBS Therapy involves the relieve of abdominal pain and discomfort and the improvement of bowel function.

Question 12

Inflammatory Bowel Disease (IBD)

Answer 12

Autoimmune disorder
Chron’s disease or ulcerative colitis

Question 13

Dicyclomine and Hyoscyamine

Answer 13

Antispasmodics

Primarily act through anticholinergic activities - inhibit muscarinic cholinergic receptors in the enteric plexus and on smooth muscle

Taken as needed before meals

Adverse effects:
Sedation, dry mouth, dry hot skin, constipation, urine retention, loss of visual accommodation.
Less CNS effects with the quaternary ammonium compounds

Question 14

Lubiprostone

Answer 14

Prostanoic acid derivative that stimulates type 2 chloride channel (CIC-2) in the small intestine

For the treatment of women with IBS with predominant constipation, chronic constipation, and opioid-induced constipation

Not well absorbed from the GI so few system effects, however still nausea, diarrhea, flatulence, bloating, GI distress, and headaches

NOT FOR PREGNANT WOMEN

Question 15

Linaclotide

Answer 15

14-aa synthetic peptide that activates guanylate cyclase C receptors on luminal surface of intestinal epithelium (See notes for specifics)

Treatment of chronic idiopathic constipation and irritable bowel syndrome with constipation (in adults)

Adverse effects: diarrhea, abdominal pain, flatulence, and abdominal distension. Category C drug.
NOT FOR <18 yo

Question 16

Inflammatory Bowel Disease

Answer 16

Chronic, idiopathic inflammation of the intestine that results in diarrhea, abdominal pain, bleeding, anemia, and weight loss.

Two classes:

Crohn’s disease (CD): Inflammation extends through all layers of the bowel wall, most often of the terminal ileum.
Ulcerative colitis (UC): Mucosal ulcers and infiltration of the colonic and/or rectal mucosa with neutrophils, macrophages, and lymphocytes.

Question 17

Aminosalicylates

Answer 17

Class of drugs containing 5-aminosalicylic acid that work topically to modulate inflammatory mediators (Inhibit COX and lipoxygenase pathways, nuclear factor kappa-B, and cellular functions of immune cells)

80% absorbed in small intestine

First line treatment of mild to moderate active Ulcerative colitis and relief of colonic Crohn’s disease however no mucosal healing

Adverse effects: nausea. vomiting, diarrhea, headache, abdominal pain

Contraindictions
- Sulfasalazine: Patients allergic to sulfonamides
- All aminosalicylates - Patients allergic to salicylates

Question 18

Azo compounds (Aminosalicylates)

Answer 18

Contain two 5-ASA bound by azo (N=N) to reduce absorption in the small intestine.
High concentrations of active drug are made available in the terminal ileum and colon - bacteria cleave azo
Includes sulfasalazine

Question 19

Oral glucocorticoids (prednisone) and Budesonide

Answer 19

Glucocorticoids

Inhibit production of inflammatory cytokines and chemokines

Short term treatment for acute mild to moderate UC or CD. Requires maintenance therapy otherwise relapse common.

Budesonide notes:
-Enteric released formulation (entocort) or rectal foam (Uceris) available

Question 20

Infliximab

Answer 20

Anti-Tumor Necrosis Factor Therapy

Monoclonal antibody that binds and inactivates the cytokine TNF-alpha and suppresses immune function

Must be given IV and is approved for moderate to severe UC and CD.

Adverse effects of infections due to immuno-suppression and allergic reactions.

Question 21

Lactase and Alpha-galactosidase (Beano)

Answer 21

Digestive enzymes that aid digestion of food materials in patients with enzyme deficiencies or pancreatic disease

Question 22

Simethicone

Answer 22

Anti-flatulence (anti-gas) agent
Surface active, anti-foaming agent that facilitates the formation of large gas bubbles in the upper GI tract. Causes burping instead of passing gas.

Used alone or in combination, widely used with questionable efficacy.