Gastric Disease State Drugs Flashcards
Histamine production Outline
Amino acids stimulate histidine production. Histidine is converted to histamine by L-histidine decarboxylase.
Histamine at equilibrium
Mono-cation
H1 Receptor Function
mucus secretion, Venule permeabilisation (leaky blood vessels), endothelial contraction (blood pressure drop) and smooth tissue contractions (tightening of throat). Allergic Response
H2 Receptor Function
Gastric acid stimulant and immune system modulation
H3 Receptor Function
Neuromodulation
2 confirmations of histamine
trans (H1 and H2 activations) and gauche (H3 activation)
Trans Histamine Confirmation Outline
Amine group and ring are at 180 degrees angle to each other when looking down main bond.
Gauche Histamine Confirmation Outline
Amine group and ring are at an angle less then 180 degrees from eachother
Enterochromaffin-like cells
Histamine store. Innervated H2 muscarinic (Ach) and CCKb (gastrin) receptors
Result of released histamine
Parietal cells are stimulated to release gastric acid via cAMP dependent pathway
Conditions H2 receptor antagonists are used in
Duodenal/gastric ulcers, GORD, upper GI bleeding and hypersensitivity (allergy - effects H1 aswell)
H2 Antagonists Development
From study of partial H2 Antagonists, Imidazole derivatives (starting with guanyl histamines).
How adding CH3 benefits selectivity
Better binding to H2 receptors
Burimamide Outline
1st derivative of imidazole. Orally inactive
Metiamide Outline
2nd derivative of imidazole. Adding of a 2nd sulfur in place of the methyl group and replacing the H on the imidazole with a methyl group
Cimetidine Outline
3rd derivative of imidazole. Replacement of the terminal sulfur with CN2
Helicobacter Pylori Outline
Small, curved, highly motile, gram negative, bacillus bacteria. Causes peptic ulcer disease in mucous layer of stomach (risk factor for developing gastric cancer)
H. Pylori Urease Function
Enzyme that breaks urea into ammonia and bicarbonate. Used in diagnostic breath tests. Intake of C13 into body causes breakdown of urea into ammonia with C13
How is pH gradient made in stomach
H pylori in stomach lining produce bicarbonate when breaking down urea. The closer to stomach lining = the more neutral the pH
Protein Pump Inhibitors Outline
Inhibits all gastric acid stimulating pathways: Ach, gastrin and histamine. Inhibits K+-H+ ATPase pump by covalent binding. prevents H+ entering lumen, preventing H+ and Cl- combining to prevent HCl forming
PPIs development Outline
Clefting of toxic side chain and adding of bandizipole ring. Lipophilic, weak base and understable
Chiral Sulfur Outline
Sulfur with 3 different molecular substituents and a bond with a lone pair of electrons (4 bonds of different substituents in total)
Why does the configuration of omeprazole in acid catalysed activation
Sulfur begins chiral, becomes a more closed system in second derivation and the loses chirality in 3rd derivation
Cytoprotective and prostaglandins
Antisecretory effects, prostaglandin E analogues and orally active
Antisecretory Effects
Inhibits adenylcyclase (decrease cAMP) and stimulates mucus and bicarbonate productions
sucralfate Outline
sucrose sulfuric acid ester and Al(OH)3. Insoluble ulcer exudate (crosslinking protective membrane over ulcer). Inhibits pepsin
Bismuth Effects
Protective ulcer coating with antimicrobrial effects. Bismuth quadruple therapy
Prokinetic Agents Outline
Enhance peristalsis and gastric emptying. Partial 5HT4 agonists release acetyl choline. Can have serios drug interactions
