GI Disorders 2: Gastric Acid Secretion Flashcards
Gastric Secretion
what is in gastric juice?
What are peptic ulcers?
What is GERD?
- gastric juice includes proenzymes (prorennin, pepsinogen), HCl, intrinsic factor
- disturbances in secretions - peptic ulcer, GERD
Peptic ulcers: open sores on inside lining of stomach and upper portion of SI
GERD: stomach acid frequently flows back into esophagus
Parietal cells
What do they do?
what do they express?
- secrete isotonic solution of HCl
- expresses K+ proton ATPase which pumps protons (H+/K+ ATPase) into the stomach lumen for gastric juice
Stimulators of parietal cell acid output (3)
- histamine
- gastrin
- acetylcholine
Inhibitors of parietal cell acid output (2)
- prostaglandin E2/I2 (majority of cells in GI)
- somatostatin (peptide secreted by D cells)
- somatostatin not selective so it is not controlled
G cells
secrete?
- in gastric antrum, secrete gastrin
- gastrin releases CCK
- stimulate parietal cells (and ECL cells)
- this axis is dominant controlling mechanism of acid
Neuroendocrine cells (enterochromaffin like cells)
secrete?
- secrete histamine which acts on parietal cells through H2 receptors to increase cAMP
- stimulate acid output
Mucus-secreting cells
secrete? (2)
pH?
- mucus-secreting cells are abundant in the gastric mucosa
- create a gel-like protective barrier
- secrete HCO3-
- secrete mucin
- maintains mucosal surface pH at 6-7
H. pylori
- peptic ulcers
- G- bacillus
- chronic gastritis
- inflamm induces G cells to secrete gastrin
- increase risk of stomach cancer
- therapy w/ antibiotics and reduce ulcer symptoms
Agents for treating peptic ulcers or GERD (3 general)
- antisecretory agents
- buffers
- cytoprotectants (act on mucus layer)
Histamine H2 Receptor Antagonists
Name (ending)
efficacy compared to PPIs?
- cimetidine, ranitidine, nizatidine, famotidine
- can be IM/IV except famotidine
- less efficacious than PPIs
Histamine H2 Receptor Antagonists
MOA?
decrease?
promote?
- competitively ant. histamine actions
- reduce parietal cell cAMP levels
- used to inhibit acid secretion, reduce histamine and gastrin induced acid secretion
- decrease basal and food stimulated acid secretion
- promote healing of gastric duodenal ulcers
Histamine H2 Receptor Antagonists
AE (2 main)
- rare AE
- *gynecomastia, galactorrhea, decrease in sexual function in men (cimetidine only)
- *thrombocytopenia (low platelet count) due to suppression of bone marrow
Proton Pump Inhibitors
Name (ending)
- omeprazole, esomeprazole, lansoprazole, pantoprazole, rabeprazole
- most potent for treating acid, directly act on pump
- oral, can be injected
Proton Pump Inhibitors
MOA?
how long does this last?
- weak base
- accumulates in acid environment of canaliculi of parietal cell
- binds to proton pump irreversible
- reduce the amount of H+ pumped into stomach lumen
- effect stays until new proton pumps are made
Proton Pump Inhibitors
AE (1)
- well tolerated generally
- *hypergastrinemia
- not enough acid so G cells secrete more gastrin which can be cancerous
- may mask symptoms of gastric cancer
- not for pregnant/breastfeeding women, liver disease
Misoprostol
MOA (3)
receptor?
- oral stable analogue of prostaglandin E1
- acts directly on prostaglandin EP2/3 receptors on ECL cells to inhibit basal and food-induced gastric acid secretion
- may contribute to maintenance of mucosal barrier
- stimulates mucin (EP4 receptor) and bicarbonate (EP1/2 receptor)
- promotes healing of ulcers
- prevent gastric damage with chronic NSAID use
Misoprostol
AE (1)
- diarrhea - strong GI contractions
- abdominal cramps
- *uterine contractions - avoid in pregnancy
Antacids
Types (2)
- salts of magnesium or aluminum
- MgOH2 - insoluble powder that forms MgCl2 in stomach
- Al(OH)3 forms Al(Cl)3
Antacids
MOA (2)
- neutralize acid and inhibit activity of peptic enzymes
- healing of duodenal ulcers if given for a long enough time (less effective for gastric ulcers)
Antacids
AE
difference b/w the 2?
- mag salts are fast acting and cause diarrhea
- al salts are slow acting and cause constipation
- mixture of 2 preserve normal bowel function
- poorly absorbed drugs and can chelate certain drugs
- prescribed with simeticone (anti-foaming agent to relieve bloating)
Drugs the protect mucosa
Name (2)
Bismuth chelate (Pepto bismol) - OTC for mild GI symptoms
Sucralfate
Bismuth chelate
MOA (3)
- toxic on bacillus, prevent H. pylori adherence to mucosa
- forms protective barrier over ulcer and enhances prostaglandins, mucus, bicarbonate secretion
- inhibit proteolytic enzymes
Bismuth chelate
AE (3)
- nausea, vomiting
- blackening of tongue and feces as bismuth reacts with H2S to make bismuth sulfide
- tinnitus
- encephalopathy (Reye’s Syndrome) if renal excretion impaired (not for kids) - brain damage due to chelation
Sucralfate
MOA
- complex of al hydroxide and sulfated sucrose that forms a viscous paste in acidic media (releases aluminum)
- binds positively charge proteins in ulcer forming a barrier for 6 hours to protect lining
- reduces degradation of mucus via pepsin
- stimulate secretion of mucus, bicarbonate, prostaglandins (unknown mech)
Sucralfate
AE
- minimal systemic
- rare constipation due to Al, toxicity
Treatment of H. pylori infection
what kind of therapy?
- rapid, long-term healing of ulcers
- triple therapy with antibiotics to eradicate infection and a PPI to reduce symptoms
- amoxicillin, metronidazole, clarithromycin, tetracycline
What is the dominant mechanisms controlling acid secretion?
gastrin-ECL-parietal cell axis
G cells release gastrin which acts on CCK receptor of ECL cell and causes histamine release which binds to H2R on parietal cell causing H+ release
What releases ACh?
Effect?
postganglionic cholinergic neruons release ACh
act on M3R of parietal cell to cause H+ release
Somatostatin
where in the axis does it act?
effect?
secreted by?
- act on SST2R receptors of G cells, ECL cells, parietal cells
- inhibits H+ release
- stomach D cells secrete somatostatin
Why is there a risk of ulcer with NSAID use?
- NSAID blocks AA in being formed to PGE2 which would normally act on EP2/3 receptor on ECL cells and downstream inhibit acid release of parietal cells.
- overproduction of acid that can damage stomach
