Lilley: Pharmacology and the Nursing Process, 9th Edition
Chapter 50: Acid-Controlling Drugs
Key Points
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 One stomach condition requiring drug therapy is hyperacidity, or excessive acid
production. Left untreated, hyperacidity can lead to serious conditions such as acid
reflux, ulcer disease, esophageal damage, and even esophageal cancer.
Anatomy, Physiology, and Disease Overview
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The stomach secretes many substances (hydrochloric acid, pepsinogen, mucus,
bicarbonate, intrinsic factor, and prostaglandins).
The gastric glands are highly specialized secretory glands composed of several different
types of cells: parietal, chief, mucous, endocrine, and enterochromaffin.
Parietal cells produce and secrete hydrochloric acid (HCl). They are the primary site of
action for many of the drugs used to treat acid-related disorders.
Chief cells secrete pepsinogen. Pepsinogen is a proenzyme (enzyme precursor) that
becomes pepsin when activated by exposure to acid. Pepsin breaks down proteins and is
therefore referred to as a proteolytic enzyme.
Mucous cells are mucus-secreting cells that are also called surface epithelial cells. The
secreted mucus serves as a protective coating against the digestive action of HCl and
digestive enzymes.
In acid-related disorders, there is an impairment of the balance among the substances
secreted by the stomach.
The most harmful of the acid-related diseases involve hypersecretion of acid and include
peptic ulcer disease and esophageal cancer. The most common condition is mild to
moderate hyperacidity.
Hyperacidity is often associated with gastroesophageal reflux disease (GERD). This is
the tendency of excessive and acidic stomach contents to back up, or reflux, into the
lower (and even upper) esophagus. Over time, this condition can lead to more serious
disorders such as erosive esophagitis and Barrett esophagus, a precancerous condition.
HCl maintains the environment of the stomach at a pH of 1 to 4. This acidity aids in
digestion and also serves as one of the body’s defenses against microbial infection via the
gastrointestinal (GI) tract.
Several substances stimulate HCl secretion by the parietal cells, such as food, caffeine,
chocolate, and alcohol. In moderation, any of these is usually not problematic.
Excessive consumption of large, fatty meals or alcohol, as well as emotional stress, may
result in hyperproduction of HCl and lead to hypersecretory disorders such as peptic ulcer
disease.
Peptic ulcer disease is a general term for gastric or duodenal ulcers that involve digestion
of the GI mucosa by the enzyme pepsin.
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Because the process of ulceration is driven by the proteolytic (protein breakdown) actions
of pepsin together with the caustic effects of HCl, peptic ulcer disease and related
problems are also referred to by the more general term acid-peptic disorders.
Helicobacter pylori (H. pylori) is implicated in the pathophysiology of peptic ulcer
disease. The prevalence of H. pylori as measured by serum antibody tests is
approximately 40% to 60% for patients older than 60 but only 10% for those younger
than 30 years of age.
H. pylori is found in the GI tracts of roughly 90% of patients with duodenal ulcers and
70% of those with gastric ulcers. First-line therapy includes a 10- to 14-day course of a
proton pump inhibitor and the antibiotics clarithromycin and either amoxicillin or
metronidazole.
Stress-related mucosal damage is an important issue for critically ill patients. Stress
ulcer prophylaxis is used in almost all patients in intensive care units (ICUs) and some
on general medical surgical units.
GI lesions are common in ICU patients, especially in the 24 hours after admission.
Factors include decreased blood flow, mucosal ischemia, hypoperfusion, and
reperfusion injury. Guidelines suggest that all such patients receive either a histamine
receptor–blocking drug or a proton pump inhibitor.
Pharmacology Overview
Antacids
 Antacids are basic compounds used to neutralize stomach acid. Most commonly they are
nonprescription salts of aluminum, magnesium, calcium, and/or sodium.
 Many antacid preparations contain the antiflatulent drug simethicone, which reduces gas
and bloating.
 Many aluminum- and calcium-based formulations also include magnesium, which not
only contributes to the acid-neutralizing capacity but also counteracts the constipating
effects of aluminum and calcium.
 Antacids work primarily by neutralizing gastric acidity. They do not prevent the
overproduction of acid but instead help to neutralize acid secretions. It is also believed
that antacids promote gastric mucosal defensive mechanisms, especially at lower
dosages.
 The primary drug effect of antacids is the reduction of the symptoms associated with
various acid-related disorders, such as pain and reflux.
 Antacids are indicated for the acute relief of symptoms associated with peptic ulcer,
gastritis, gastric hyperacidity, and heartburn.
 Adverse effects of antacids are limited. Magnesium preparations, such as milk of
magnesia, can cause diarrhea. Aluminum- and calcium-containing formulations can cause
constipation.
 Magnesium-aluminum combination antacids are used to prevent the adverse effects of
constipation and diarrhea. Some of the more serious concerns with antacids include acid
rebound, hypercalcemia, milk-alkali syndrome, and metabolic alkalosis.
 Combination products containing both magnesium and aluminum may have fewer
adverse effects than either type of antacid by itself. The net effect is a balancing of both
adverse effects and fewer problems with altered bowel patterns.
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An adverse effect more common with the calcium-containing products is rebound
hyperacidity, in which the patient has hyperacidity when antacid use is discontinued.
Cautious use of antacids high in sodium is recommended in patients who have heart
failure, hypertension, or other cardiac diseases or who require sodium restriction.
Many drug interactions occur with the acid-controlling drugs due to alteration of oral
dosage forms, and so other medications are to be avoided within 1 to 2 hours of taking
an antacid. Antacids are sometimes to be avoided when other acid-controlling drugs are
taken.
Four basic mechanisms by which antacids cause interactions include adsorption of other
drugs to antacids, which reduces the ability of the other drug to be absorbed into the
body; chelation, which is the chemical inactivation of other drugs that produces insoluble
complexes; increased stomach pH, which increases the absorption of basic drugs and
decreases the absorption of acidic drugs; and increased urinary pH, which increases the
excretion of acidic drugs and decreases the excretion of basic drugs.
Significant patient harm may ensue when the quinolone antibiotics (ciprofloxacin,
levofloxacin, moxifloxacin) are given with antacids.
Some of the more serious concerns with antacids include acid rebound, hypercalcemia,
milk-alkali syndrome, and metabolic alkalosis.
H2 Receptor Antagonists
 H2 receptor antagonists, also known as H2RAs and H2 receptor blockers, are the
prototypical acid-secretion antagonists. They are H2 blockers that bind to and block
histamine receptors located on parietal cells. This blockade renders these cells less
responsive to stimuli and thus decreases their acid secretion. Up to 90% inhibition of acid
secretion can be achieved.
 The effect of reduced hydrogen ion secretion from the parietal cells results in an increase
in the stomach pH and relief of symptoms associated with hyperacidity-related
conditions.
 H2 receptor antagonists are used for GERD, peptic ulcer disease, and erosive esophagitis;
adjunct therapy in the control of upper GI tract bleeding; and treatment of pathologic
gastric hypersecretory conditions such as Zollinger-Ellison syndrome.
 The H2 receptor antagonists include the drugs cimetidine, ranitidine, famotidine, and
nizatidine.
 Ranitidine (Zantac) has many fewer drug interactions compared to cimetidine and has
become the most widely used H2 receptor antagonist.
 Cimetidine carries a higher risk of drug interactions than ranitidine, famotidine, and
nizatidine, especially in elderly. Cimetidine binds enzymes of the hepatic cytochrome P450 microsomal oxidase system, liver enzymes that metabolize many different drugs. By
inhibiting the metabolism of drugs metabolized via this pathway, it may raise the blood
concentrations of certain drugs.
 All drugs in this class are available over the counter.
Proton Pump Inhibitors
 Drugs used for the treatment of acid-related disorders are the proton pump inhibitors
(PPIs). These include lansoprazole (Prevacid), omeprazole (Prilosec), rabeprazole
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(AcipHex), pantoprazole (Protonix), esomeprazole (Nexium), and dexlansoprazole
(Dexilant). Zegerid is a combination of omeprazole and sodium bicarbonate.
The PPIs bind directly to the hydrogen-potassium-ATPase pump mechanism and
irreversibly inhibit the action of this enzyme, resulting in total blockage of hydrogen ion
secretion. PPIs block the final step in the acid production pathway, the hydrogenpotassium-ATPase pump, and they block all acid secretion.
PPIs are currently indicated as first-line therapy for erosive esophagitis, symptomatic
GERD that is poorly responsive to other medical treatment such as therapy with H2
receptor antagonists, short-term treatment of active duodenal ulcers and active benign
gastric ulcers, gastric hypersecretory conditions (e.g., Zollinger-Ellison syndrome),
nonsteroidal antiinflammatory drug (NSAID)–induced ulcers, and for stress ulcer
prophylaxis.
All PPIs can be used in combination with antibiotics to treat H. pylori infections.
When omeprazole is given with clopidogrel, there is some concern of a decrease in
clopidogrel’s effectiveness due to the fact that clopidogrel is dependent on its conversion
to an active metabolite by the CYP-450 enzyme system, specifically CYP2C19.
PPIs are generally well tolerated.
The U.S. Food and Drug Administration issued a warning in 2010 regarding long-term
use of high-dose PPIs, which has been associated with Clostridium difficile infections;
risk of wrist, hip, and spine fractures; and pneumonia. In 2011, depletion of magnesium
was added to the warning.
PPIs may increase serum levels of diazepam and phenytoin and there may be an
increased chance of bleeding in patients who are taking both a PPI and warfarin.
Miscellaneous Acid-Controlling Drugs
 There are a few other acid-controlling drugs that are unique in terms of their mechanisms
and other features, including sucralfate, misoprostol, and simethicone.
 Sucralfate is used for the treatment of peptic ulcer disease and stress-related ulcers. It
binds to tissue proteins in the eroded area and prevents exposure of the ulcerated area to
stomach acid.
 Misoprostol (Cytotec) is a synthetic prostaglandin analog that inhibits gastric acid
secretion and is used to prevent NSAID-related ulcers.
 Simethicone (Mylicon) is used to reduce the discomforts of gastric or intestinal gas
(flatulence) and aid in its release via the mouth or rectum.
Nursing Process
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Before an acid-controlling drug is given, perform a thorough patient assessment with
attention to past and present medical history and with special focus on GI tract–related
disorders and signs and symptoms of ulcer disease and GERD.
Since acid-controlling drugs have many interactions, underscore the importance of
obtaining a medication history about prescription drugs, over-the-counter drugs, and
herbals.
The high sodium content of various antacids may lead to exacerbation of cardiac
problems, renal dysfunction, and fluid-electrolyte problems.
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With quinolone antibiotics, there may be serious harm if given with antacids because of a
50% reduction in antibiotic absorption.
For patients using H2 receptor antagonist drugs, assess renal and liver function and level
of consciousness. Elderly patients react to these drugs with more disorientation and
confusion.
Do not administer drugs such as cimetidine and famotidine simultaneously with antacids.
Since there are documented concerns about the use of PPIs and development of
osteoporosis, thoroughly assess patients for any history of this disorder.
The use of simethicone and sucralfate requires assessment of the patient’s bowel patterns
and bowel sounds and evaluation for abdominal distention and rigidity.
When giving acid-controlling drugs, instruct the patient to thoroughly chew the chewable
tablets and to thoroughly shake liquid forms. Antacids need to be given with at least 8 oz
of water to enhance absorption, except for newer forms that are rapidly dissolving drugs.
For all of these H2 receptor antagonists, monitor blood pressure readings as needed
during intravenous infusion because of the risk of hypotension. Continue to monitor the
patient for GI tract bleeding with the diagnosis of ulcers or GI irritation. Report any blood
in the stools or the occurrence of black, tarry stools or hematemesis.
With PPIs, give lansoprazole oral dosage forms as ordered and with fluids. Monitor for
abdominal pain, distention, and abnormal bowel sounds.
Always double-check the names and dosages of these drugs to ensure that they are not
confused with similarly named drugs.
Therapeutic response to the administration of antacids, H2 receptor antagonists, PPIs, and
other related drugs includes the relief of symptoms associated with peptic ulcer, gastritis,
esophagitis, gastric hyperacidity, or hiatal hernia (i.e., decrease in epigastric pain,
fullness, and abdominal swelling).
Adverse effects range from constipation or diarrhea to nausea, vomiting, abdominal pain,
and hypotension. Milk-alkali syndrome, acid rebound, hypercalcemia, and metabolic
alkalosis are known complications associated with the various antacids.
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