Chapter 50 AcidControlling Drugs Copyright 2014 by Mosby

Acid-Related Pathophysiology The stomach secretes: Hydrochloric acid (HCl) Ø Bicarbonate Ø Pepsinogen Ø Intrinsic factor Ø Mucus Ø Prostaglandins Ø Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 2

Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 3

Glands of the Stomach Cardiac Pyloric Gastric Ø The cells of the gastric gland are the largest in number and of primary importance when discussing acid control Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 4

Cells of the Gastric Gland Parietal Chief Mucous Endocrine Enterochromaffin Copyright © 2014 by

Cells of the Gastric Gland (cont’d) Parietal cells Produce and secrete HCl Ø Primary site of action for many of the drugs used to treat acid-related disorders Ø Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 6

Parietal Cell Stimulation and Secretion Copyright © 2014 by Mosby, an imprint of Elsevier

Cells of the Gastric Gland Chief cells Secrete pepsinogen, a proenzyme Ø Pepsinogen becomes pepsin when activated by exposure to acid Ø Pepsin breaks down proteins (proteolytic) Ø Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 8

Cells of the Gastric Gland (cont’d) Mucous cells Mucus-secreting cells (surface epithelial cells) Ø Provide a protective mucus coat Ø Protect against self-digestion by HCl and digestive enzymes Ø Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 9

Hydrochloric Acid Secreted by parietal cells when stimulated by food, caffeine, chocolate, and alcohol Maintains stomach at p. H of 1 to 4 Acidity aids in the proper digestion of food and defenses against microbial infection via the GI tract Secretion also stimulated by: Large fatty meals Ø Emotional stress Ø Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 10

Acid-Related Diseases Peptic ulcer disease (PUD) Ø Gastric or duodenal ulcers that involve digestion of the GI mucosa by the enzyme pepsin Helicobacter pylori (H. pylori) Bacterium found in GI tract of 90% of patients with duodenal ulcers and 70% of those with gastric ulcers Ø First-line therapy includes a 10 - to 14 -day course of a proton pump inhibitor and antibiotics Ø Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 11

Acid-Related Diseases (cont’d) Stress-related mucosal damage GI lesions are a common finding in ICU patients, especially within the first 24 hours after admission Ø Factors include decreased blood flow, mucosal ischemia, hypoperfusion, and reperfusion injury Ø Nasogastric (NG) tubes and ventilators predispose patients to GI bleeding Ø A histamine receptor–blocking drug or a proton pump inhibitor are given for prevention Ø Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 12

Types of Acid-Controlling Drugs Antacids H 2 antagonists Proton pump inhibitors Copyright © 2014

Antacids Basic compounds used to neutralize stomach acid Salts of aluminum, magnesium, calcium, and/or sodium Many antacid preparations also contain the antiflatulent (antigas) drug simethicone Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 14

Antacids: Mechanism of Action Do not prevent the overproduction of acid but instead help to neutralize acid secretions Promote gastric mucosal defensive mechanisms Stimulate secretion of: Mucus: protective barrier against HCl Ø Bicarbonate: helps buffer acidic properties of HCl Ø Prostaglandins: prevent activation of proton pump Ø Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 15

Antacids: Drug Effects Reduction of pain associated with acid-related disorders Raising gastric p. H 1 point (1. 3 to 2. 3) neutralizes 90% of the gastric acid Ø Reducing acidity reduces pain as a result of: • Base-mediated inhibition of the protein-digesting ability of Ø pepsin • Increase in the resistance of the stomach lining to irritation • Increase in the tone of the cardiac sphincter Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 16

Antacids (cont’d) Over-the-counter formulations available as: Capsules and tablets Ø Powders Ø Chewable tablets Ø Suspensions Ø Effervescent granules and tablets Ø Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 17

Antacids (cont’d) Used alone or in combination Aluminum salts Ø Magnesium salts Ø Calcium

Antacids: Aluminum Salts Have constipating effects Often used with magnesium to counteract constipation Often recommended for patients with renal disease (more easily excreted) Examples Aluminum carbonate: Basaljel Ø Hydroxide salt: Alterna. GEL Ø Combination products (aluminum and magnesium): Gaviscon, Maalox, Mylanta, Di-Gel Ø Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 19

Antacids: Magnesium Salts Commonly cause diarrhea; usually used with other drugs to counteract this effect Dangerous when used with renal failure—the failing kidney cannot excrete extra magnesium, resulting in accumulation Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 20

Antacids: Magnesium Salts (cont’d) Examples Hydroxide salt: magnesium hydroxide (Milk of Magnesia) Ø Carbonate salt: Gaviscon (also a combination product) Ø Combination products such as Maalox, Mylanta (aluminum and magnesium) Ø Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 21

Antacids: Calcium Salts Many forms, but carbonate is most common May cause constipation, kidney stones Also not recommended for patients with renal disease—may accumulate to toxic levels Long duration of acid action—may cause increased gastric acid secretion (hyperacidity rebound) Often advertised as an extra source of dietary calcium Ø Example: Tums (calcium carbonate) Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 22

Antacids: Sodium Bicarbonate Highly soluble Buffers the acidic properties of HCl Quick onset, but short duration May cause metabolic alkalosis Sodium content may cause problems in patients with heart failure, hypertension, or renal insufficiency Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 23

Classroom Response Question A patient who has chronic renal failure wants to self-treat with an antacid for occasional heartburn. Which medication is the best choice for this patient? A. A magnesium-containing antacid B. A calcium-containing antacid C. An aluminum-containing antacid D. Because of renal problems, the patient should not take antacids for this problem. Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 24

Antacids and Antiflatulents: used to relieve the painful symptoms associated with gas Several drugs are used to bind or alter intestinal gas and are often added to antacid combination products Ø simethicone Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 25

Antacids: Adverse Effects Minimal and depend on the compound used Aluminum and calcium • Constipation Ø Magnesium • Diarrhea Ø Calcium carbonate • Produces gas and belching; often combined with simethicone Ø Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 26

Antacids: Drug Interactions Adsorption of other drugs to antacids Ø Reduces the ability of the other drug to be absorbed into the body Chelation Chemical binding, or inactivation, of another drug Ø Produces insoluble complexes Ø Result: reduced drug absorption Ø Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 27

Antacids: Drug Interactions (cont’d) Increased stomach p. H Increased absorption of basic drugs Ø Decreased absorption of acidic drugs Ø Increased urinary p. H Increased excretion of acidic drugs Ø Decreased excretion of basic drugs Ø Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 28

Histamine 2 (H 2) Receptor Antagonists Reduce acid secretion All available over the counter in lower dosage forms Most popular drugs for treatment of acid-related disorders cimetidine (Tagamet) Ø nizatidine (Axid) Ø famotidine (Pepcid) Ø ranitidine (Zantac) Ø Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 29

H 2 Antagonists: Mechanism of Action Competitively block the H 2 receptor of acidproducing parietal cells Reduced hydrogen ion secretion from the parietal cells Increase in the p. H of the stomach Relief of many of the symptoms associated with hyperacidity-related conditions Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 30

H 2 Antagonists: Drug Effect and Indications Drug effect Ø Suppressed acid secretion in the stomach Indications Gastroesophageal reflux disease (GERD) Ø Peptic ulcer disease (PUD) Ø Erosive esophagitis Ø Adjunct therapy to control upper GI bleeding Ø Zollinger-Ellison syndrome Ø Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 31

H 2 Antagonists: Adverse Effects Overall, very few adverse effects Central nervous system adverse effects in elderly patients include confusion and disorientation Cimetidine may induce impotence and gynecomastia Thrombocytopenia has been reported with ranitidine and famotidine Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 32

H 2 Antagonists: Drug Interactions cimetidine (Tagamet) Binds with P-450 microsomal oxidase system in the liver, resulting in inhibited oxidation of many drugs and increased drug levels Ø All H 2 antagonists may inhibit the absorption of drugs that require an acidic GI environment for absorption Ø Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 33

H 2 Antagonists: Drug Interactions (cont’d) Smoking has been shown to decrease the effectiveness of H 2 blockers For optimal results, H 2 receptor antagonists are taken 1 to 2 hours before antacids Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 34

Classroom Response Question When working with an elderly patient who has been admitted for a possible gastrointestinal bleed, the nurse identifies which drug as having the potential to cause confusion and disorientation? A. B. C. D. An antacid A proton pump inhibitor An H 2 antagonist A mucosal protectant Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 35

Proton Pump Inhibitors (PPIs) The parietal cells release positive hydrogen ions (protons) during HCl production This process is called the proton pump H 2 blockers and antihistamines do not stop the action of this pump Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 36

Proton Pump Inhibitors lansoprazole (Prevacid) omeprazole (Prilosec) rabeprazole (Acip. Hex) pantoprazole (Protonix) esomeprazole (Nexium)

Proton Pump Inhibitors: Mechanism of Action Irreversibly bind to H+/K+ ATPase enzyme This bond prevents the movement of hydrogen ions from the parietal cell into the stomach Results in achlorhydria—ALL gastric acid secretion is temporarily blocked Ø To return to normal acid secretion, the parietal cell must synthesize new H+/K+ ATPase Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 38

Proton Pump Inhibitors: Indications GERD Erosive esophagitis Short-term treatment of active duodenal and benign gastric ulcers Zollinger-Ellison syndrome Nonsteroidal antiinflammatory drug (NSAID)– induced ulcers Stress ulcer prophylaxis Treatment of Helicobacter pylori–induced ulcers Ø Given with an antibiotic Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 39

Proton Pump Inhibitors: Adverse Effects PPIs are generally well tolerated Possible predisposition to GI tract infections (Clostridium difficile) Osteoporosis and risk of wrist, hip, and spine fractures in long-term users Pneumonia Depletion of magnesium Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 40

Miscellaneous Acid-Controlling Drugs sucralfate (Carafate) misoprostol (Cytotec) simethicone (Mylicon) Copyright © 2014 by Mosby,

Sucralfate (Carafate) Cytoprotective drug Used for stress ulcers, peptic ulcer disease Attracted to and binds to the base of ulcers and erosions, forming a protective barrier over these areas Protects these areas from pepsin, which normally breaks down proteins (making ulcers worse) Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 42

Sucralfate (Carafate) (cont’d) Little absorption from the gut May cause constipation, nausea, and dry mouth May impair absorption of other drugs—give other drugs at least 2 hours before sucralfate Do not administer with other medications Binds with phosphate; may be used in chronic renal failure to reduce phosphate levels Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 43

Misoprostol (Cytotec) Prostaglandin E analog Prostaglandins have cytoprotective activity Protect gastric mucosa from injury by enhancing local production of mucus or bicarbonate Ø Promote local cell regeneration Ø Help to maintain mucosal blood flow Ø Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 44

Misoprostol (Cytotec) (cont’d) Used for prevention of NSAID-induced gastric ulcers Doses that are therapeutic enough to treat duodenal ulcers often produce abdominal cramps, diarrhea Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 45

Simethicone Antiflatulent drug Used to reduce the discomforts of gastric or intestinal gas (flatulence) Alters elasticity of mucus-coated gas bubbles, breaking them into smaller ones Result is decreased gas pain and increased expulsion via mouth or rectum Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 46

Classroom Response Question Simethicone (Mylicon) is often combined with calcium carbonate antacids because: A. an increased antacid effect will result when these drugs are given in combination. B. simethicone helps to reduce the gas that is caused by the calcium antacids. C. simethicone reduces the diarrhea that is caused by the calcium. D. simethicone improves the taste of the calcium tablets, which must be chewed. Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 47

Nursing Implications: Antacids Assess for allergies and preexisting conditions that may restrict the use of antacids, such as: Ø Ø Ø Fluid imbalances Renal disease GI obstruction Heart failure (HF) Pregnancy Patients with heart failure or hypertension should not use antacids with high sodium content Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 48

Nursing Implications: Antacids (cont’d) Use with caution with other medications because of the many drug interactions Most medications should be administered 1 to 2 hours after an antacid Antacids may cause premature dissolving of enteric-coated medications, resulting in stomach upset Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 49

Nursing Implications: Antacids (cont’d) Be sure that chewable tablets are chewed thoroughly, and liquid forms are shaken well before giving Administer with at least 8 ounces of water to enhance absorption (except for “rapid-dissolve” forms) Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 50

Nursing Implications: Antacids (cont’d) Long-term self-medication with antacids may mask symptoms of serious underlying diseases, such as malignancy or bleeding ulcers If symptoms remain ongoing, patient should seek medical evaluation Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 51

Nursing Implications: Antacids (cont’d) Monitor for adverse effects Nausea, vomiting, abdominal pain, diarrhea Ø With calcium-containing products: constipation, acid rebound Ø Monitor for therapeutic response Ø Notify health care provider if symptoms are not relieved Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 52

Nursing Implications: H 2 Antagonists Assess for allergies and impaired renal or liver function Use with caution in patients who are confused, disoriented, or elderly Take 1 to 2 hours before antacids For intravenous doses, follow administration guidelines Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 53

Nursing Implications: Proton Pump Inhibitors Assess for allergies and history of liver disease Not all are available for parenteral administration May increase serum levels of diazepam and phenytoin; may increase chance for bleeding with warfarin Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 54

Nursing Implications: Proton Pump Inhibitors (cont’d) The granules of pantoprazole capsules may be given via nasogastric (NG) tubes, but the NG tube must be at least 16 gauge or the tube may become clogged Capsule contents may be opened and mixed with apple juice, but do not chew or crush delayed-release granules Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 55

Classroom Response Question When providing education regarding the use of proton pump inhibitors, which statement will the nurse include? A. “Take the medication along with the first meal of the day. ” B. “Take the medication on an empty stomach, 30 to 60 minutes before eating. ” C. “Take the medication when you have symptoms of heartburn. ” D. “Take the medication at bedtime with a snack. ” Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 56