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gipharm1.html
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<!DOCTYPE html>
<html lang="en">
<head>
<meta charset="utf-8">
<meta http-equiv="X-UA-Compatible" content="IE=edge">
<meta name="viewport" content="width=device-width, initial-scale=1">
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<title>Ginger_Jungle, DMD (tbd)</title>
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</head>
<nav class="navbar navbar-default navbar-static-top" style="background-color:rgba(255,255,255,.7);">
<div class="container-fluid">
<div class="navbar-header">
<a class="navbar-brand" href="index.html">Preston's Site</a>
</div>
<ul class="nav navbar-nav">
<li><a href="index.html">Home</a></li>
<li class="dropdown">
<a href="#" class="dropdown-toggle" data-toggle="dropdown" role="button" aria-haspopup="true" aria-expanded="false">Gastrointestinal Unit<span class="caret"></span></a>
<ul class="dropdown-menu">
<li><a href="anatomy.html">Overview and Anatomy</a></li>
<li><a href="secretions.html">GI secretions</a></li>
<li><a href="swallow.html">Swallowing</a></li>
<li><a href="disorders.html">GI Disorders</a></li>
<li><a href="hormones.html">Hormones</a></li>
<li><a href="gidisorders1.html">GI Disorders I</a></li>
</ul>
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<li class="dropdown">
<a href="#" class="dropdown-toggle" data-toggle="dropdown" role="button" aria-haspopup="true" aria-expanded="false">Pharmacology<span class="caret"></span></a>
<ul class="dropdown-menu">
<li class="active"><a href="gipharm1.html">GI Pharmacology I</a></li>
<li><a href="gipharm2.html">Disorders of GI Function</a></li>
<li><a href="endocrinepharm1.html">Endocrine Pharmacology I</a></li>
<li><a href="endocrinepharm2.html">Endocrine Pharmacology II</a></li>
<li><a href="endocrinepharm3.html">Endocrine Pharmacology III</a></li>
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<h1>GI Pharmacology - Acid-Peptic Disorders and Prokinetics</h1>
<br><br>
</div>
<div class="container text-left">
<div style="font-size:16px">
<ol>
<li>Dyspepsia - indigestion</li>
<ul>
<li>Can be caused by GERD or Peptic Ulcer disease</li>
<li>Peptic ulcer disease is gastric and duodenal, and can be stress-induced</li>
<li>Dyspepsia is alleviated by <b>reducing gastric acid</b></li>
</ul>
<li>Antacids neutralize gastric acid, inhibit pepsin activity, and are safe</li>
<li>Antacids are composed of an acid and a weak base</li>
<ul>
<li>Sodium bicarbonate</li>
<li>Calcium carbonate (Tums) can cause hypercalcemia with excessive use</li>
<li>Calcium can be beneficial (osteoporisis) or detrimental - may increase risk
of MI and kidney stones</li>
<li>Aluminum hydroxide - no CO2, so doesn't cause belching, but is constipating</li>
<li>Magesium hydroxide - no CO2, can promote diarrhea</li>
<li>Fewer problems with hydroxide due to less alkalinization</li>
<li>Antacids can slow absorption of other drugs through chelation - sodium bicarbonate does not do this</li>
<li>Use of antacids with other drugs should be separated by 2 hours</li>
<li>Impaired renal function can decrease excretion of absorbed metals</li>
</ul>
<li>Reducing Gastric Acid - H2 antagonists</li>
<ul>
<li>-tidine family - Cimetidine, Ranitidine, Famotidine, etc. ("to dine")</li>
<li>H2 histamine receptor selectivity, antagonism is reversible</li>
<li>Rapid intestinal absorption, all have first pass metabolism (except Nizatidine)</li>
<li>Liver metabolism and urinary excretion are important for elimination</li>
<li>Ranitidine removed from marketing over concern of NMDA carcinogen contamination, drug itself was safe</li>
<li>Cimetidine inhibits CYP450 1A2, 2D6, 3A4, increasing blood levels of Warfarin, Phenytoin, Theophylline, and CCBs</li>
<li>H2 antagonists are particularly effective at blocking nocturnal acid secretion</li>
</ul>
<li>Proton Pump Inhibitors - the "prazole" family</li>
<ul>
<li>All are "prodrugs" - usually administered orally in enteric-coated capsule</li>
<li>Food reduces absorption</li>
<li>Dissolution occurs in intestines</li>
<li>Compounds are lipophilic weak bases</li>
<li>Diffuse to acidic parietal cells and protonate, trapping the weak base</li>
<li>Converted into reactive intermediate which covalently binds to ATPase, takes a dase for effects to show</li>
<li>Short half life but irreversible inhibition</li>
<li>QD dosing for Peptic ulcer, BID for GERD</li>
<li>Helicobacter pylori can cause a rapid relapse, usually in cases of peptic ulcer - treat with two drug antibiotic therapy</li>
<li>Reduced vitamin/mineral absorption - B12 and Mg</li>
<li>Changes normal flora - increases susceptibility to enteric infection</li>
<li>Increased gastrin signaling - elevated pH, positive feedback, increases number of ECL cells, possibly carcinogenic</li>
<li>Reduces clopidogrel efficacy through CYP2C19 inhibiton - Clopidogrel is a prodrug</li>
<li>PPIs can increase risk of Clostridium difficule infection, bone fractures (Mg++ malabsorption),
community-acquired pneumonia in elderly patients</li>
</ul>
<li>Mucosal protection - enhance mucosal defense against acid and digestive enzymes</li>
<li>Sucralfate, Postaglandins, Bismuth subsalisylate</li>
<li>Sucralfate forms a viscous paste, creating a barrier to acid and digestive enzymes ("stick" to gastric lesions)</li>
<ul>
<li>Stimulates prostaglandin release, bicarbonate secretion</li>
<li>Safe and effective - little absorbed, can cause constipation</li>
</ul>
<li>Misoprostil</li>
<ul>
<li>PGE1 analog with short half life</li>
<li>Stimulates intestinal contractions, mucosal blood flow, bicarbonate secretion</li>
<li>Inhibits cAMP accumulation in parietal cells</li>
<li>Used for prophylaxis of NSAID ulcers</li>
<li>Contraindicated in pregnancy</li>
</ul>
<li>Bismuth Subsalisylate</li>
<ul>
<li>Dissociates in stomatch, salisylate is absorbed for renal excretion, bismuth coats lesion and eliminated fecally</li>
<li>Salisylate inhibits prostaglandin release and is bacteriocidal</li>
<li>Bismuth binds enterotoxins, useful in diarrhea caused by microbes</li>
<li>Can cause black tongue and stool, constipation, salicylate toxicity</li>
</ul>
</ol>
</div>
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