Lecture 13 - Pharmacology of the Gastrointestinal Tract Flashcards
(53 cards)
What triggers the cephalic phase?
Sight, smell, taste, or thought of food stimulates the vagus nerve which in turn stimulates gastric secretion (hydrochloric acid, pepsin)
What happens during the gastric phase?
Partially digested food stretches the stomach and activates myenteric and vagovagal nerve reflexes –> stimulate gastric secretions
What stimulatory molecules are present in the stomach during the gastric phase?
Histamine and gastirin
What happens during the intestinal phase?
Sypmpathetic nerve fibers suppress gastric activity while parasympathetic (vagal) stimulation of the stomach is inhibited.
What inhibits gastric secretion during the intestinal phase?
Secretin, cholecystokinin (CCK), and the enterogastric reflex
Describe the gastric cycle
1) ingested food buffers, stomach acid, elevating pH
2) elevated pH stimulates G cells that make up the pyloric gland
3) G cells secrete gastrin
4) Gastrin stimulates the chief cells and parietal cells on the gastric gland
5a) ACH, H2, and gastrin receptors on enterochromafflin-like cells secrete histamine
5b) Chief cells secrete pepsinogen
5c) Parietal cells secrete HCl
6) HCl converts pepsinogen to pepsin
7) Pepsin digests dietary protein
8a) Partially digected protein oligopeptides and amino acids buffer the stomach acid –> elevates pH
8b) Partially digested protein oligopeptides directly stimulate G cells
What molecules stimulate HCl secretion and where are they formed?
- Acetylcholine- parasympathetic postganglionic neurons
- gastrin- G cells
- histamine- neuroendocrine cells
What molecules inhibit HCl release?
CCK, somatostatin, and secretin
Where is pepsinogen (precursor to pepsin) secreted?
Chief (peptic) cells
What cells secrete somatostatin?
D cells
What do surface mucus cell secrete when stimulated?
Bicarbonate and mucus
- stimulated by prostagladins
What is secretin?
A digestive hormone
How are gastrin and cholecystokinin (CCK) related?
They are structurally and functionally related peptide hormones
What is somatostatin?
A cyclic peptide present in the GI tract, pancreas, and CNS
What type of receptors are somatostatin receptors?
Inhibitory GPCRs
What are Octreotide and Lanreotide and their uses?
- Mimic the action of somatostatin (act on somatostatin receptors located on gastric parietal cells)
- Clinical use for gastrinomas, gastric ulcers, and other disorders associated with excessive gastric acid secretion
What is a peptic ulcer?
An open sore that develop on the mucosal lining of the stomach and duodenum, where acid and pepsin activity are greatest
What are the symptoms of peptic ulcers?
- Periodic pain, nausea, vand vomitting
- loss of appetite
- heartburn
- perforation in the GI wall
Possible causes of peptic ulcers
- Helicobacter pylori
- Long-term use of NSAIDs
- Hyperacidity (genetic, environmental, inflammation)
How does H. pylori cause peptic ulcer?
- inflammatory mediators elicited by H. pylori inhibit somatostatin secretion by D cells –> disinhibition of gastrin release
- H. pylori produces ammonium hydroxide which increases gastric pH –> stimulates gastrin secretion
How do NSAIDs cause peptic ulcer disease?
- NSAIDs inhibit COX –> reduce production of prostaglandins –> increased gastric acid secretion, decreased bicarbonate/mucus production and blood flow
- Increased expression of intercellular adhesion molecules –> increeased neutrophil adherence to vascular endothelial cells –> mucosal damage due to neutrophil-derived free radicals and proteases
How does Bismuth and Antibiotics treat peptic ulcer?
Inhibit the H. pylori bacteria
What drugs are used to treat peptic ulcers?
- H2 blockers
- Muscarinic antagonists
- Proton pump inhibitors
- Antacids
- Coating agents
What do antihistamine receptor antagonists (H2 blockers) do?
Reduce interactions between histamine and H2 receptors –> pepsin and acid secretion decreases