What is irritable bowel syndrome (IBS)?
Challenging to treat
Constipation (IBS-C), diarrhea (IBS-D), or mixed
Bowel symptoms managed as noted (laxatives or anti-diarrheals)
Abdominal pain very hard to treat
What drugs are used for IBS and pain?
Calcium antagonists (GI tracts)
What are anticholinergics?
Muscarinic (M) receptors stimulate peristalsis in the GI tract (rest and digest)
Blocking M receptors inhibits contractions of the colon
Side effects: dry mouth, urinary retention, constipation (usual anticholinergic affects)
What are calcium antagonists?
Blocks entry of Ca into smooth muscle cells of the GI tract
Ca plays critical role in smooth muscle contraction
Therefore blocking Ca inhibits smooth muscle contraction
Side effects: constipation, abdominal distension, esophageal irritational
What is linaclotide?
Cyclic guanosine monophosphate (cGMP) agonist
Increases intestinal secretions
Reduces transmission of pain signals
What is inflammatory bowel disease (IBD)?
Sever inflammation (and it’s destructive)
Can involve anywhere along the GI tract
2 major types: Ulcerative colitis (limited time colon) Crohn’s disease
Inflammation can destroy intestinal mucosa (painful)
Complications like bleeding, perforation, sepsis
What is used to treat inflammatory bowel disease (IBD)?
Inflammation and immune responses are the key processes in the disease
What are aminosalicylates used in IBD?
5-aminosalicylic acid (5-ASA or mesalamine)
Anti-inflammatory activity, inhibits inflammatory mediators including tumour necrosis factor (TNFα), also may inhibit cyclooxygenase (COX)
Prodrugs cleaves to colon, enteric coating dissolved in colon, microspheres releasing drug slowly, rectal administration
Side effects: GI (worse than sulfasalazine), headache,
What is the prodrug aminosalicylates?
5-ASA + sulfapyridine
2 molecules separated in colon by bacteria
What is enteric coating in aminosalicylates?
Enteric coating (EC)
Delayed release of 5-ASA, based on pH (drug not released in low pH of stomach)
Begin releasing drug in terminal ileum, continue through to rectum
What are extended release (ER) microspheres in aminosalicylates?
Release 5-ASA throughout the small intestine to rectum
What are corticosteroids used in IBD?
Budesonide has low oral bioavailability (intended to act locally in GI tract
Anti inflammatory effects
Side effects: numerous with systemic agents like prednisone, fewer side effects with budesonide
What is microbiota with health and disease?
Increasing recognition of the role of bacteria in general health, both good and bad bacteria
Small intestinal bacteria overgrowth is a phenomena where there is excess bacteria in the gut
Many ways to treat IBS may be to target gut bacteria with an antibiotics (rifaximin)