Lecture 21 - AntiDiarrheal Drugs, IBS, and IBD Flashcards
Absorbents
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)
Bulk Forming Agents (Dietary Fiber)
Bind excess water to yield partially formed stool.
Do not decrease the bulk of fecal material
Bismuth Subsalicylate
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)
Paregoric
Opium extract (w/ morphine)
Inhibit peristalsis through circular smooth muscle constriction and longitudinal muscle relaxation.
Not used often anymore, replaced by loperamide.
Loperamide
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)
Toxic Megacolon (Symptom)
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.
Hyoscyamine, Dicyclomine (Other: atropine, homatropine, belladonna extracts, glycopyrrolate, propantheline, isopropamide)
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.
Citrate and salicylate, Pepto-Bismol
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)
Sulfasalazine
For inflammatory bowel disease.
Sulfapyridine (antimicrobial) and salicylate (anti-inflammatory) together.
Side effects: allergic reactions, hemolytic anemia, blood dyscrasias (similar to sulfonamides)
Mesalamine
Sulfasalazine that can be given orally or by retention enema for the treatment of ulcerative colitis.
Irritable Bowel Syndrome (IBS-D and IBS-C)
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.
Inflammatory Bowel Disease (IBD)
Autoimmune disorder
Chron’s disease or ulcerative colitis
Dicyclomine and Hyoscyamine
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
Lubiprostone
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
Linaclotide
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
Inflammatory Bowel Disease
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.
Aminosalicylates
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
Azo compounds (Aminosalicylates)
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
Oral glucocorticoids (prednisone) and Budesonide
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
Infliximab
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.
Lactase and Alpha-galactosidase (Beano)
Digestive enzymes that aid digestion of food materials in patients with enzyme deficiencies or pancreatic disease
Simethicone
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.
