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    Peptic Ulcers: PHRM 304

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    Apurba Sarker Apu
    Peptic ulcers are mucosal erosions in the stomach or duodenum that are usually caused by Helicobacter pylori bacteria or NSAID drugs like aspirin. Gastric acid secretion is regulated by parietal cells in the stomach which release acid in response to histamine, acetylcholine, and gastrin. Histamine is released by neighboring enterochromaffin-like cells and stimulates parietal cells through H2 receptors. Treatment options for peptic ulcers include antacids, acid inhibitors, mucosal protectants, and antibiotics to treat H. pylori infections.

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    Peptic Ulcers: PHRM 304

    Uploaded by

    Apurba Sarker Apu
    468 views24 pages
    Peptic ulcers are mucosal erosions in the stomach or duodenum that are usually caused by Helicobacter pylori bacteria or NSAID drugs like aspirin. Gastric acid secretion is regulated by parietal cells in the stomach which release acid in response to histamine, acetylcholine, and gastrin. Histamine is released by neighboring enterochromaffin-like cells and stimulates parietal cells through H2 receptors. Treatment options for peptic ulcers include antacids, acid inhibitors, mucosal protectants, and antibiotics to treat H. pylori infections.

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    Antiulcerant Introduction

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    Antiulcerant Introduction

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    Peptic ulcers are mucosal erosions in the stomach or duodenum that are usually caused by Helicobacter pylori bacteria or NSAID drugs like aspirin. Gastric acid secretion is regulated by parietal cells in the stomach which release acid in response to histamine, acetylcholine, and gastrin. Histamine is released by neighboring enterochromaffin-like cells and stimulates parietal cells through H2 receptors. Treatment options for peptic ulcers include antacids, acid inhibitors, mucosal protectants, and antibiotics to treat H. pylori infections.

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    Attribution Non-Commercial (BY-NC)
    Download as PPTX, PDF, TXT or read online from Scribd
    Download as pptx, pdf, or txt
    468 views24 pages

    Peptic Ulcers: PHRM 304

    Uploaded by

    Apurba Sarker Apu
    Peptic ulcers are mucosal erosions in the stomach or duodenum that are usually caused by Helicobacter pylori bacteria or NSAID drugs like aspirin. Gastric acid secretion is regulated by parietal cells in the stomach which release acid in response to histamine, acetylcholine, and gastrin. Histamine is released by neighboring enterochromaffin-like cells and stimulates parietal cells through H2 receptors. Treatment options for peptic ulcers include antacids, acid inhibitors, mucosal protectants, and antibiotics to treat H. pylori infections.

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    Peptic Ulcers

    PHRM 304

    Peptic ulcer
    A peptic ulcer, also known as PUD or peptic ulcer disease, is an ulcer (defined as mucosal erosions equal to or greater than 0.5 cm). As many as 70-90% of ulcers are associated with Helicobacter pylori, a spiral-shaped bacterium that lives in the acidic environment of the stomach.

    Peptic ulcer
    Ulcers can also be caused or worsened by drugs such as aspirin, Clopidogrel, ibuprofen, and other NSAIDs.

    Peptic ulcers

    Physiology of gastric acid secretion


    - Gastric acid (HCl) is produced by parietal cells of the oxyntic gland in the gastric mucosa.

    - Produces 2-3 liters of gastric juice per day.


    -Maintains stomach at a pH of 1 to 4. - Chief cell produce pepsinogen which is converted to pepsin by HCl.

    Gastric (oxyntic) gland

    Enterochromaffin-like (ECL) Cell


    Enterochromaffin-like cells (ECL cells) in the gastric mucosa produce, store & release histamine activated by acetylcholine (M1 receptors), gastrin (CCK2 receptors). Acetylcholine and gastrin release activated by food stimulation and also by some secretagogues: Caffeine and theophylline Peptides Spices Alcohol Aspirin

    Parietal cell
    Parietal cells produce gastric acid (hydrochloric acid) in response to histamine (via H2 receptors), acetylcholine (M3 receptors) and gastrin (CCK2 receptors). The histamine receptors act by increasing intracellular cAMP, whereas the muscarinic and gastrin receptors increase intracellular Ca2+ levels.

    Parietal cells contain a hydrogen ion pump (proton pump), a unique H+/K+ ATPase system that secretes H+ in exchange for the uptake of the K+ ion. The HCl acid is formed at the lumen of the canaliculi and then conducted through openings to the gastric lumen.

    Gastric lumen

    Fig: Canaliculi in parietal cell

    Canalicui
    A canaliculus is an adaptation found on gastric parietal cells. It is a deep infolding, or little channel, which serves to increase the surface area, e.g. for secretion. The membrane of parietal cells is dynamic; the numbers of canaliculi rise and fall according to secretory need.

    Resting

    Secreting

    CCK2

    Parasympathetic fiber Acetylcholine +

    G cell in blood release Gastrin + CCK2

    M1 ECL cells

    Histamine

    M3
    1

    2 3 CCK2 Parietal cell

    1. Acetylcholine receptor 2. H2 receptor 3. Gastrin receptor

    Hydrochloric acid

    Fig: Factors influence gastric acid secretion

    Fig: Factors influence gastric acid secretion

    Mechanism of Action

    Physiology of acid secretion


    The parietal cell contains receptors for gastrin (CCK2), histamine (H2), and acetylcholine (muscarinic, M3). When acetylcholine or gastrin bind to the parietal cell receptors, they cause an increase in cytosolic calcium, which in turn stimulates protein kinases that stimulate acid secretion from a H+/K+ ATPase (the proton pump) on the canalicular surface.

    In close proximity to the parietal cells are gut endocrine cells called enterochromaffin-like (ECL) cells. ECL cells have receptors for gastrin (CCK2) and acetylcholine (probably M1) and are the major source for histamine release. Histamine binds to the H2 receptor on the parietal cell, resulting in activation of adenylyl cyclase, which increases intracellular cyclic adenosine monophosphate (cAMP). cAMP activates protein kinases that stimulate acid secretion by the H+/K+ ATPase. In humans, it is believed that the major effect of gastrin upon acid secretion is mediated indirectly through the release of histamine from ECL cells rather than through direct parietal cell stimulation.

    Drugs used in peptic ulcers


    - Antacids
    Neutralize pathology. secreted acid. No effect on underlying

    - Inhibitors of gastric acid production


    H2 receptor antagonists Proton pump inhibitors Muscarinic receptor antagonists Gastrin receptor antagonist

    - Mucosal protectant
    Decrease HCl & pepsin secretion & increase mucous production.

    - Anti-Helicobacter pylori. drugs

    Antacids: hydroxide

    Aluminum

    hydroxide,

    Magnesium

    H2 receptor antagonists: Cimetidine, Ranitidine

    Muscarinic receptor antagonists: Atropine (M3 receptor), pirenzipine (M1 receptor)


    Proton pump inhibitor: Omeprazole Gastrin receptor antagonist: Proglumide Mucosal protectants: Misoprostol (prostaglandin analogues)

    Anti-Helicobacter pylori. Drugs: Antibiotics (commonly use triple therapy: one proton pump inhibitor-lansoprazole and two antibioticsamoxicillin and clarithromycin) These options are also effective:

    Figure: A schematic illustration of the secretion of hydrochloric acid by the gastric parietal cell.

    Histamine
    Histamine is a hydrophilic molecule comprising an imidazole ring with a ethylamine side-chain.

    Histamine exists as monocation at blood pH (7.4) Under physiological conditions, the aliphatic amino group (having a pKa around 9.4) will be protonated, whereas the second nitrogen of the imidazole ring (pKa 5.8) will not be protonated.

    Interaction of histamine with receptor:


    1. Electrostatic attraction between protonated N of histamine side chain and receptor (-ve charge site)

    2. H-bonding between imidazole N and receptor


    3. H-bonding receptor between imidazole N-H and

    In aqueous solution histamine exists in two tautomeric forms, N-H-histamine and N-Hhistamine.

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