Ex. 6 - GI Protection (61-62) Flashcards
Drugs affecting gastric secretion
Antacids
H2 histamine receptor antagonists
PPIs
Protectants
Drugs that increase GI motility
Laxatives
Prokinetic drugs
Reduce GI motility
Anti-diarrheals
Anti-emetics
Acid-peptic disease drugs used in tx of
Non-ulcer dyspepsia (indigestion)
Gastric and duodenal ulcers
GERD - Barrett’s Esophagus
Hypersecretory states such as Zollinger- Ellison syndrome
^Rare
Tumors that produce gastrin
Physiologic control of GI secretions
Parietal cell
in epithelium of stomach
Secretes acid into the lumen of stomach
**stimulated by activation of M3 receptors, AcH, histamine (H2 receptors) and gastrin
Conversion: Proton ATPase
-Moves protons into the stomach
-It does so by moving potassium into the parietal cell
Why do we have sensitivity to receptors in the parietal cell?
These are physiological modulators on the acid secretion of gastrin
Gastrin released in response to food intake
-Directly stimulates parietal cells
-Stimulates ECL cells
ECL Cells
Contain granules of histamine
Gastrin stimulation stimulates the release of histamine
Feedback loop
Lumen of the stomach = highly acidic: inhibitory signal for further acid secretion
-Achieved through activation of D cells which release Somatostatin
Inhibits release of gastrin
-Yellow in graphic
Make up the most of the endothelium of the stomach
Surface epithelial cells
Surface epithelial cells
Secrete mucus and bicarbonate within lumen of the stomach
-Protects underlying tissue from acid erosion
Mucus is a physical barrier - within mucus bicarbonate secreted by surface epithelial cells and creates a buffer within mucus to help neutralize and protect stomach
Prostaglandins (PGE2 and PGI2)
Persistent innovation of prostaglandin synthesis protects the stomach
-Protects through mucosa
Systemically absorbed Antacids
NaHCO3
Neutralizing capacity: High
Adverse: Systemic alkalosis, fluid retention; excess gas
(CO2)
CaCO2
Neutralizing capacity: Moderate
Adverse: Hypercalcemia, nephrolithhiasis, milk-alkali syndrome (CO2)
Minimally absorbed antacids
Al(OH)3
Neutralizing capacity:
High
Adverse:
Constipation, hypophosphatemia if absorbed; encephalopathy
Mg(OH)2
Neutralizing capacity:
High
Adverse:
Diarrhea
If absorbed: CNS toxicity
Commercial Antacids
AlternaGEL - AL(OH)3
Tums - CaCO3
Maalox, Mylanta - Al(OH3) and Mg(OH)2
Rolaids - CaCO3 & Mg(OH)2
Alka-Seltzer - ASA and NaHCO3
Gaviscon (sodium alginate + antacids) - Viscous, weak base
-Prevents reflux
Effective in GERD
Chewable tabs vs liquid suspension
-Liquid more popular but more expensive
H2 Histamine Receptor Antagonists - Cimetidine (Tagamet)
Competitive antagonist of H2 Histamine Receptor
-Reduce gastric acid secretion in response to histamine, gastrin, AcH
H2 Histamine Receptor Antagonists - second gen
Ranitidine
-No longer available
Nizatidine
Famotidine
Competitive antagonists of H2 histamine receptor
Reduce gastric acid secretion in response to histamine, AcH, gastrin
Longer half-life (Hs vs. BID dosing)
Fewer effects on CYP450 system
Greater potency
Absorbed quickly to reduce parietal cell function
PPIs
Main target for acid secretion in the stomach
-Red section on graphic
-inhibiting ultimate step of pathway
-Can suppress acid secretion of M2/3, Gastrin, and H2 receptors by blocking P
PPI types - Bezimidazoles
Esomeprazole (Nexium), omeprazole (prilosec)
-Same molecule, eso is purified S enantiomer - slightly more potent
Lansoprazole (Prevacid)
Raberprazole (Aciphex)
Panntoprazole (Protonix)
Dexlansoprazole (Dexilant)
PPI MOA
Have to be activated in the acidic environment of parietal cell
-essentially irreversible mechanism
-Why the drugs have such a long half-life
-You would have to replace the proton pumps to fix
*8Summary of PPI actions**
Must be absorbed in the SI (acidic), circulate and then be taken up by the parietal cells. This leads to slow onset
Prodrugs: Activated by acidic pH (IN the parietal cell)
Irreversible inhibitor of H+/K+-ATPase (Cys813)
Short plasma half-life (1hour) but long duration of action due to covalent inhibition (24hrs) and slow turnover of proton pumps
Hypergastrinemia occurs, and MAY result in rebound hypersecretion of gastric acid upon drug withdrawal