Summary

This document is a class presentation on gastrointestinal drugs, focusing on peptic ulcer disease. It covers different medication classes, mechanisms of action, and related client care.

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Gastrointestinal Drugs Peptic Ulcer Disease Chapter 82 Objectives Review GI physiology and the effect of hydrochloric acid in digestion Distinguish between the medication classes: antacids, H2 antagonists, Proton pump inhibitors and miscellaneous acid-control agents Describe the mecha...

Gastrointestinal Drugs Peptic Ulcer Disease Chapter 82 Objectives Review GI physiology and the effect of hydrochloric acid in digestion Distinguish between the medication classes: antacids, H2 antagonists, Proton pump inhibitors and miscellaneous acid-control agents Describe the mechanism of action, indications, contraindications, interactions of, effects and adverse effects of the 3 classes Identify a prototype medication for each classification and its related information including some select pharmacokinetic information Develop understanding of related client care Stomach Acid-Related Diseases Stomach secretes Hydrochloric acid (HCl; parietal cells) Pepsinogen (chief cells) Mucus Bicarbonate Prostaglandins Body Parietal cells ECL cells Chief cells Pyloric Gland Area G cells Stomach Cell Types Parietal cells Produce and secrete HCl to keep stomach at pH of 1 to 2 Primary site of action for many acid-controller drugs ECL cells Secrete histamine stimulate parietal cells Stomach Acid-Related Diseases Action of acidity on digestive tract integrity Lay terms for stomach problems indigestion, sour stomach, heartburn, acid stomach PUD: peptic ulcer disease GERD: gastroesophageal reflux disease Drug Therapies Eradicate H. pylori if present in stomach Reduce gastric acidity Enhance mucosal defences Stomach Acid-Related Diseases Helicobacter pylori (H. pylori) found in 90% of clients with duodenal ulcers, and 70% of those with gastric ulcers Antibacterials are used to eradicate H. pylori Recurrence rates much less with eradication See later slide for treatment regimen Inhibitors of Gastric Acid Secretion/ Action H2 antagonists Proton pump inhibitors Antacids Magnesium salts Calcium salts Sodium bicarbonate Aluminium salts Other Agents – Protect mucosa H2 Antagonists H2 Antagonists Reduce acid secretion All available OTC in lower dosage forms Most popular drugs for treatment of acid- related disorders Cimetidine (Tagamet) some drug interactions so less used famotidine (Pepcid) ranitidine (Zantac) nizatidine (Axid) H2 Antagonists: Mechanism of Action Block histamine H2 receptors of acid- producing parietal cells Receptor antagonist Decreased production of HCl H2 Antagonists: Indications GERD (gastro-esophogeal reflux disease) Erosive esophagitis PUD (peptic ulcer disease) Adjunct therapy in control of upper GI bleeding Pathological gastric hypersecretory conditions H2 Antagonists: Adverse Effects Low incidence of adverse effects Cimetidine may induce impotence and gynecomastia antiandrogenic effect In elderly may see CNS depression (eg lethargy), confusion renal/hepatic impairment H2 Antagonists: Drug Interactions cimetidine Inhibits liver cytochrome P-450 Affect metabolism of other drugs causing increased drug levels eg warfarin Client Implications: H2 Antagonists Cimetidine Care in patients with impaired renal or liver function Use with caution in patients who are confused, disoriented, or elderly Take 1 hour before or after antacids- important affects absorption Proton Pump Inhibitors (PPI) Proton Pump Inhibitors Inhibition of the pump that moves H+ into stomach lumen More effective than H2 antagonists Proton Pump Inhibitors (PPI): Mechanism of Action Irreversibly bind to H+/K+ ATPase enzyme (proton pump) normal acid secretion requires parietal cell to synthesize new H+/K+ ATPase Proton Pump Inhibitors Omeprazole (Losec or Prilosec) lansoprazole rabeprazole pantoprazole (Pantoloc) IV option esomeprazole All very similar Proton Pump Inhibitors Omeprazole (Losec or Prilosec) Enteric coated Broken down by acid! Proton Pump Inhibitors: Indications GERD maintenance therapy Erosive esophagitis Short-term treatment of active duodenal and benign gastric ulcers Zollinger-Ellison syndrome (gastrin- producing tumour) Proton Pump Inhibitors: Adverse Effects Safe for short-term therapy 4-8 weeks Incidence low and uncommon headaches, GI (nausea/vomiting/diarrhea) Use with caution in patients with liver disease Proton Pump Inhibitors: Drug Interactions May inhibit the absorption of drugs that require an acidic GI environment for absorption eg ketoconazole (antifungal drug) Stomach Acid-Related Diseases Typical Therapy for H.pylori infection “Triple Therapy” Antibacterials eg amoxicillin + clarithromycin Proton pump inhibitor eg omeprazole 7 – 14 days Client Care: Proton Pump Inhibitors Agents may increase serum levels of: diazepam BZD used in many CNS conditions (see later classes) phenytoin used in epilepsy (see later classes) cause increased chance for bleeding with warfarin P450 inhibition in liver Client Care: Proton Pump Inhibitors Instruct the client taking omeprazole: Capsule should be swallowed whole, not crushed, opened, or chewed (enteric coated) It may be given with antacids Emphasize that the treatment will be short term Antacids Antacids: Mechanism of Action Antacids chemically neutralize acid Antacids DO NOT prevent acid production Antacids OTC formulations available as: Capsules and tablets Powders Chewable tablets Suspensions Effervescent granules and tablets Antacids Used alone or in combination Aluminum salts Magnesium salts Calcium salts Sodium bicarbonate Antacids: Aluminum Salts Salts: carbonate, hydroxide may cause constipation often with magnesium salts to counteract constipation (cause diarrhoea) Examples aluminium hydroxide (Amphogel) Aluminum carbonate Combination products (aluminum and magnesium) Antacids: Magnesium Salts Salts: carbonate, hydroxide, oxide, trisilicate Commonly cause diarrhea usually used with other agents to counteract diarrhea Dangerous when used with renal failure accumulation Examples Hydroxide salt: magnesium hydroxide Carbonate salt (also a combination product) Combination products (aluminum and magnesium) Antacids Al salts (constipation) + Mg salts (diarrhea) = Normal bowel function Antacids: Calcium Salts Salts: many, but carbonate is most common May cause constipation Possible kidney stones Often advertised as an extra source of dietary calcium Example: calcium carbonate (TUMS) Antacids: Sodium Bicarbonate Highly soluble Quick onset, but short duration May cause metabolic alkalosis Sodium content may cause problems in clients with HF, hypertension, or renal insufficiency Antacids: Adverse Effects Minimal, and depend on the compound used Aluminum and calcium Constipation Magnesium Diarrhea Calcium carbonate Constipation Produces gas and belching often combined with simethicone Antacids: Drug Interactions Absorption of other drugs May reduce absorption of other drugs given at same time Chelation Chemical binding, or inactivation, of another drug Produces insoluble complexes reduced drug absorption eg tetracycline Care Implications: Antacids Assess for allergies and preexisting conditions that may restrict the use of antacids, such as: Fluid imbalances Renal disease HF Pregnancy GI obstruction Clients with HF or hypertension should use low- sodium antacids Care Implications: Antacids Root cause of many drug interactions Most medications should be given 1 to 2 hours after giving an antacid Antacids may cause premature dissolving of EC medications Tell to chew chewable tablets Administer with at least 240 mL of water to enhance dispersion, not needed if rapid dissolve form used Caffeine, alcohol, harsh spices, and black pepper may aggravate the underlying GI condition Other Agents – Protect Mucosa Sucralfate bind directly to ulcer surface Misoprostol (Cytotec) Prostaglandin agent (see NSAID class) Sucralfate Cytoprotective agent Used for intestinal erosions Forms gel with mucus in low pH do not administer with antacids Attracted to and binds to the base of ulcers and erosions forming a protective barrier Inhibits pepsin Sucralfate Little absorption from the gut May cause constipation, nausea, and dry mouth May impair absorption of other drugs eg tetracycline, digoxin Binds with phosphate may be used in chronic renal failure to reduce phosphate levels Misoprostol Synthetic prostaglandin (PGE1) analogue Does the job of endogenous PGs (PGI2 and PGE2) Prostaglandins have cytoprotective activity production of mucus and bicarbonate reduce acid secretion promote local cell regeneration help to maintain mucosal blood flow Misoprostol Misoprostol (Cytotec) To reduce gastic effects of NSAIDs e.g. ASA, diclofenac Combination tablets Arthrotec = diclofenac + misoprostol Not in pregnancy used to terminate pregnancy Misoprostol – Adverse Effects Therapeutic doses for duodenal ulcers often produce abdominal cramps, diarrhea PGE cause contraction of many smooth muscle-containing tissues

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