A.

DRUG THERAPY
Peptic ulcer patients usually are treated with antacids, histamine 2(H2)- receptor antagonists, or proton
pump inhibitors; other drugs are added as necessary. Drug regimens that suppress nocturnal acid
secretion are found to result in the highest duodenal ulcer healing rates.
Drug therapy typically provides prompt symptomatic relief and promotes ulcer healing within 4 to 6
weeks. GERD management requires more aggressive acid suppression regimens; the pharmacodynamic
end point is to maintain the pH in the esophagus at four or more.

1. ANTACIDS
These compounds, which neutralize gastric acid, are used to treat ulcer pain and heal the ulcer. Studies
show antacids and H2-receptor antagonists to be equally effective. Antacids are available as
magnesium, aluminum, or calcium. The most widely used antacids are mixtures of aluminum
hydroxide and magnesium hydroxide. Duodenal ulcers rarely occur in the absence of acid or when the
hourly maximum acid output is _ 10 mEq. Peptic activity decreases as acidity decreases; experimental
ulcer formation is inhibited by antacids; and acid-reducing operations cure ulcers.
A. MECHANISM OF ACTION AND THERAPEUTIC EFFECTS
Antacids reduce the concentration and total load of acid in the gastric contents. By increasing gastric pH,
antacids also inhibit pepsin activity. In addition, they strengthen the gastric mucosal barrier.
B. CHOICE OF AGENT
a) Non-systemic antacids- (e.g., magnesium or aluminum substances) are preferred to systemic
antacids (e.g., sodium bicarbonate) for intensive ulcer therapy because they avoid the risk of alkalosis.
b) Liquid antacid forms- have a greater buffering capacity than tablets. However, tablets are more
convenient to carry. With either dosage form, the size and frequency of doses may limit patient
compliance.
c) Antacid mixtures- (e.g., aluminum hydroxide with magnesium hydroxide) provide more even,
sustained action than single-agent antacids, and permit a lower dosage of each compound. In addition,
compounds in a mixture may interact so as to negate each other’s untoward effects. For instance, the
constipating effect of aluminum hydroxide may counter the diarrhea that magnesium hydroxide
frequently produces.
d) Calcium carbonate- usually is avoided because it causes acid rebound, may delay pain relief and
ulcer healing, and induces constipation. Another potential adverse effect of this compound is
hypercalcemia; the risk is increased if calcium carbonate is taken with milk or another alkaline substance.
Th e milk-alkali syndrome (i.e., hypercalcemia, alkalosis, azotemia, nephrocalcinosis) can also occur.
C. ADMINISTRATION AND DOSAGE
1) Antacids differ greatly in acid-neutralizing capacity (ANC), defined as the number of milliequivalents
(mEq) of a 1 N solution of HCl that can be brought to a pH of 3.5 in 15 mins. For most duodenal
ulcer patients, approximately 50 mEq/hr of available antacid is needed for ongoing neutralization of
gastric contents. Therefore, the required dosage depends on the ANC of the specific antacid.
2) In the fasting state, antacids have only a transient intragastric buffering effect (15 to 20 mins). When
ingested 1 hr after a meal, they have a much more prolonged effect, about 3 to 4 hrs; therefore,
they should optimally be taken 1 and 3 hrs aft er meals and before sleep. Consequently, the typical
antacid regimen calls for doses 1 and 3 hrs after meals and at bedtime.
3) Dosage
a. Because the ANC of antacid products varies widely, no standard dosage can be given in terms of
milliliters of suspension or number of tablets. However, patients with duodenal ulcers generally
require individual dosages of 80 to 160 mEq of ANC (equivalent to 30 to 60 mL of Mylanta or
Maalox). Th us the total daily dosage may be as much as 420 mL of Mylanta or Maalox if the
standard seven-times–daily dosing regimen is used. Because of the large doses required,
 increase in adverse effects, need for frequent administration, and poor patient compliance, their
role in the management of PUD is limited.
b. Antacid therapy usually continues for 6 to 8 weeks.
D. PRECAUTIONS AND MONITORING EFFECTS
1. Calcium carbonate- and magnesium-containing antacids should be used cautiously in patients with
severe renal disease.
2. Sodium bicarbonate is contraindicated in patients with hypertension, congestive heart failure (CHF),
severe renal disease, and edema. It should not be used for ulcer therapy.
3. All antacids should be used cautiously in elderly patients (particularly those with decreased GI
motility) and renally impaired patients.
4. Aluminum-containing antacids should be used cautiously in patients who suffer from dehydration or
intestinal obstruction.
5. Th e combination of calcium carbonate with an alkaline substance (e.g., sodium bicarbonate) and
milk may cause the milk-alkali syndrome.
6. Always check brand name extension products for major ingredient changes (i.e., Maalox Total
Stomach Relief contains bismuth subsalicylate).
7. Chronic administration of calcium carbonate-containing antacids should be avoided because of
hypercalcemia and calcium ion stimulation of acid secretion.
8. Aluminum or magnesium toxicity is unlikely in patients with normal renal function. The
encephalopathy of tissue deposition of aluminum occurs only in dialysis patients receiving aluminum
hydroxide for control of hyperphosphatemia. Chronic use of magnesium-containing antacids is not
advisable in patients with renal insufficiency.
9. Constipation can occur in patients using calcium carbonate- and aluminum-containing antacids.
10. Diarrhea is a common adverse effect of magnesium-containing antacids. If diarrhea occurs, the
patient may alternate the antacid mixture with aluminum hydroxide.
11. Hypophosphatemia and osteomalacia can occur with long-term use of aluminum hydroxide, but these
conditions can also occur with short-term use in severely malnourished patients, such as alcoholics.
E. SIGNIFICANT INTERACTIONS
Because antacids alter gastric pH and affect absorption of ingested substances, they have a high
potential for drug interactions. To ensure consistent absorption and therapeutic efficacy, orally
administered drugs should be given 30 to 60 mins before antacids.
(1) Antacids bind with tetracycline and fluoroquinolones, inhibiting the absorption and
reducing therapeutic efficacy.
(2) Antacids may destroy the coating of enteric-coated drugs, leading to premature drug
dissolution in the stomach.
(3) Antacids may interfere with the absorption of many drugs, including cimetidine,
ranitidine, digoxin, isoniazid, anticholinergics, iron products, and phenothiazines.
(4) Antacids may reduce the therapeutic effects of sucralfate.

2. H2-RECEPTOR ANTAGONISTS
These drugs may be preferred to other antiulcer agents because of their convenience and lack of effect
on GI motility. Although reasonably effective in treating mild to moderate GERD symptoms, H2-receptor
antagonists are less reliable for healing erosive esophagitis. All current choices require multiple, divided
doses for GERD management.
A. MECHANISM OF ACTION AND THERAPEUTIC EFFECTS
H2-receptor antagonists competitively inhibit the action of histamine at parietal cell receptor sites,
reducing the volume and hydrogen ion concentration of gastric acid secretions. These agonists accelerate
the healing of most ulcers.
B. CHOICE OF AGENT
Cimetidine (Tagamet), ranitidine (Zantac), famotidine (Pepcid), or nizatidine (Axid) may be
administered to treat peptic ulcers or hypersecretory states (e.g., Zollinger–Ellison syndrome).
1. Cimetidine, the first H2-receptor antagonist approved for clinical use, reduces gastric acid
secretion by approximately 50% (at a total daily dosage of 1000 mg).
2. Ranitidine, a more potent drug, causes a 70% reduction in gastric acid secretion (at a total daily
dosage of 300 mg).
3. Famotidine is the most potent H2-receptor antagonist. Aft er a 40-mg dose, mean nocturnal
gastric acid secretion is reduced by 94% for up to 10 hrs.
4. Nizatidine, the last H2-receptor antagonist marketed, causes a 90% reduction in nocturnal gastric
acid secretion for up to 10 hrs.
C. ADMINISTRATION AND DOSAGE
1) Cimetidine usually is administered orally in a dosage of 300 mg four times daily (with meals and at
bedtime) for up to 8 weeks.
a. Alternatively, duodenal ulcer patients may receive 400 mg twice daily or 800 mg at bedtime. An
800-mg bedtime dose is also effective in treating gastric ulcers.
b. Hospitalized patients may receive parenteral doses of 300 mg intravenously every 6 hrs.
c. For duodenal ulcer prophylaxis, 400 mg may be given orally at bedtime. However, the ulcer
recurs in 20–40% of patients. Cimetidine is also FDA approved for the prevention of Upper GI
bleeding at a dose of 50 mg/hr continuous infusion.

2) Ranitidine usually is given orally in a dosage of 150 mg twice daily. Duodenal ulcer patients may
receive 300 mg at bedtime, alternatively. Therapy continues for up to 8 weeks.
a. Hospitalized patients may receive ranitidine by the intravenous or intramuscular route (50 mg
every 6 to 8 hrs).
b. Prophylactic therapy may be administered to reduce the risk of ulcer recurrence. The approved
prophylactic dosage is 150 mg at bedtime.
c. Ranitidine 150 mg twice daily can be administered to maintain healing of erosive esophagitis; for
this purpose, it is better than placebo but less effective than the proton pump inhibitors.
d. Ranitidine bismuth citrate, combined with antibiotics such as clarithromycin, is indicated for
eradication of H. pylori in patients with duodenal ulcer.

3) Famotidine, administered to duodenal ulcer patients, is given in an oral dosage of 40 mg at bedtime

for acute therapy for a maximum of 8 weeks. For prophylactic therapy, the dosage is 20 mg at bedtime.
a. Hospitalized patients may receive an intravenous injection of 20 mg every 12 hrs.
b. As with cimetidine and ranitidine, the ulcer may recur aft er drug discontinuation.

(4) Nizatidine, for the treatment of duodenal ulcers, is given orally in a dosage of 300 mg once daily at
bedtime or 150 mg twice daily for up to 8 weeks. For prophylactic therapy, the dosage is 150 mg at
bedtime.

D. PRECAUTIONS AND MONITORING EFFECTS

1. Ranitidine must be used cautiously in patients with hepatic impairment. Hepatotoxicity is unusual
and occurs most often during intravenous administration. Cimetidine has also been associated with
hepatotoxicity.
2. Cimetidine may cause such hematological disorders as thrombocytopenia, agranulocytosis, and
aplastic anemia.
3. All of these agents may cause headache and dizziness. Cimetidine additionally may lead to
confusion, particularly if patients are more than 60 years of age or if the dosage is not adjusted for
 patients with decreased kidney or liver function. All agents require dosage reductions in patients
with impaired renal function.
4. Cimetidine has a weak androgenic effect, possibly resulting in male gynecomastia and impotence.
5. Cimetidine and ranitidine rarely can cause bradycardia, which is reversible on discontinuation of
therapy.
6. Evaluate H. pylori status in any patient with confirmed ulcer disease; eradication of H. pylori
reduces the need for maintenance therapy in patients with duodenal or gastric ulcers. Patients with
complicated ulcer disease should continue maintenance therapy until the eradication of H. pylori.
7. Tolerance develops frequently to H2-receptor antagonists (H2RAs) and may explain diminished
responses to these agents over time.

E. SIGNIFICANT INTERACTIONS
1. Cimetidine binds the cytochrome P450 system of the liver, and thus may interfere with the
metabolism of such drugs as phenytoin, theophylline, phenobarbital, lidocaine, warfarin,
imipramine, diazepam, and propranolol.
2. Cimetidine decreases hepatic blood flow, possibly resulting in reduced clearance of propranolol
and lidocaine.
3. Antacids impair absorption of cimetidine and ranitidine, and should be given 1 hr apart from these
drugs.
4. Concomitant use of an H2RA and an azole drug has resulted in decreased efficacy.

3. SUCRALFATE (CARAFATE)
This mucosal protectant is a nonabsorbable disaccharide containing sucrose and aluminum.

A. MECHANISM OF ACTION AND THERAPEUTIC EFFECTS

Sucralfate adheres to the base of the ulcer crater, forming a protective barrier against gastric acids and
bile salts.
1. Sucralfate’s ulcer-healing efficacy compares favorably to that of the H2RAs.
2. Duodenal ulcers respond better than gastric ulcers to sucralfate therapy.

B. ADMINISTRATION AND DOSAGE

1. An oral agent, sucralfate usually is given in a dosage of 1 g four times daily (1 hr before meals)
and at bedtime. Unless radiography or endoscopy documents earlier ulcer healing, therapy
continues for 4 to 8 weeks.
2. Continued sucralfate therapy aft er remission postpones ulcer relapse more effectively than
cimetidine therapy does.
3. Th ere is no evidence that combining sucralfate with H2RAs improves healing or reduces
recurrence rates.

C. PRECAUTIONS AND MONITORING EFFECTS

Constipation is the most common adverse effect of sucralfate.

D. SIGNIFICANT INTERACTIONS
1. Antacids may reduce mucosal binding of sucralfate, decreasing its therapeutic efficacy, and
thus, should be given 30 to 60 mins apart from sucralfate if used in combination ulcer therapy.
2. Sucralfate may interfere with the absorption of orally administered digoxin, tetracycline,
phenytoin, iron, ciprofloxacin and other fluoroquinolones, and cimetidine if doses are
given simultaneously.
4. GI ANTICHOLINERGICS
GI Anti-cholinergic (e.g., belladonna leaf, atropine, propantheline) sometimes are used as adjunctive
agents for relief of refractory duodenal ulcer pain. However, these agents have no proven value in ulcer
healing.
A. MECHANISM OF ACTION
Anticholinergics decrease basal and stimulated gastric acid and pepsin secretion.
1. Given in combination with antacids, anticholinergics delay gastric emptying, thereby prolonging
antacid retention. They are most effective when taken at night and in large doses.
2. Anticholinergics occasionally are used in patients who do not respond to H2RAs alone.
B. ADMINISTRATION AND DOSAGE
1. Taken 30 mins before food, anticholinergics inhibit meal-stimulated acid secretion by 30% to 50%
for a duration of 4 to 5 hrs.
2. The optimal effective dose varies from patient to patient.
C. PRECAUTIONS AND MONITORING EFFECTS
1. All anticholinergics have side effects to varying degrees, such as dry mouth, blurred vision,
tachycardia, urinary retention, and constipation.
2. These drugs are contraindicated in patients with gastric ulcers because they prolong gastric
emptying. They also are contraindicated in patients with narrow-angle glaucoma and urinary
retention.

5. PROSTAGLANDINS
These agents suppress gastric acid secretion and may guard the gastric mucosa against damage from
NSAIDs. Misoprostol (Cytotec) has been approved for use in the prevention of gastric ulcers caused by
NSAIDs.
A. MECHANISM OF ACTION
Misoprostol has both antisecretory (inhibiting gastric acid secretion) and mucosal protective properties.
NSAIDs inhibit prostaglandin synthesis, and a deficiency of prostaglandin within the gastric mucosa may
lead to diminishing bicarbonate and mucus secretion, contributing to the mucosal damage caused by
NSAIDs. Misoprostol increases bicarbonate and mucus production at doses of 200 mcg and above—doses
that can also be antisecretory. Misoprostol also maintains mucosal blood flow.
B. ADMINISTRATION AND DOSAGE
1. Misoprostol is indicated for the prevention of NSAID-induced gastric ulcers in patients at high risk
for complications from gastric ulcers (e.g., patients more than 60 years of age, patients with
concomitant debilitating disease, patients with a history of ulcers).
2. Misoprostol has not been shown to prevent duodenal ulcers in patients taking NSAIDs.
3. The recommended adult dosage is 200 mcg four times daily with food; it must be taken for the
duration of NSAID therapy. If this dose cannot be tolerated, 100 mcg four times daily can be used.
4. Adjustment of dosage in renally impaired patients is not routinely needed.
C. PRECAUTIONS AND MONITORING EFFECTS
1. Misoprostol is contraindicated in pregnant women because of its abortifacient property. Patients
must be advised of the abortifacient property, and warned not to give the drug to others.
2. Misoprostol should not be used in women with childbearing potential unless the patient requires
NSAID therapy, and is at high risk of complications from gastric ulcers associated with use of the
NSAIDs or is at high risk of developing gastric ulceration. In such a patient, misoprostol may be
prescribed if the patient:
 a. Is capable of complying with effective contraceptive measures
b. Has received both oral and written warnings of the hazards of misoprostol, the risk of
possible contraception failure, and the danger to other women of childbearing potential
should the drug be taken by mistake
c. Had a negative serum pregnancy test within 2 weeks before beginning therapy
d. Will begin misoprostol only on the second or third day of the next normal menstrual
period
3. The most frequent adverse effects are diarrhea (14% to 40%) and abdominal pain (13% to 20%).
Diarrhea is dose related, usually develops early in the course (_ 2 weeks), and is often self-limiting.
Discontinuation of misoprostol is necessary in about 2% of patients. Administration with food
minimizes the diarrhea.
D. SIGNIFICANT INTERACTIONS- None has been reported.

6. PROTON PUMP INHIBITORS (PPIS)

Omeprazole (Prilosec) was the first PPI available in the United States, followed by lansoprazole
(Prevacid), rabeprazole (AcipHex), pantoprazole (Protonix), esomeprazole (Nexium), and
dexlansoprazole (Kapidex). Th e intravenous forms of esomeprazole, lansoprazole, and pantoprazole
have been approved by the U.S. Food and Drug Administration (FDA).
A. MECHANISM OF ACTION AND THERAPEUTIC EFFECTS
The gastric proton pump H_/K_-ATPase has a sulfhydryl group near the potassium-binding site on the
luminal side of the canalicular membrane. Omeprazole sulfonamide (the active form) forms a stable
disulfide bond with this specific sulfhydryl, thereby inactivating the ATPase and shutting off acid
secretion. All other PPIs exhibit a similar irreversible mechanism of action.
1. Because of the potency and marked reduction in gastric acidity, the PPIs are more rapidly effective
than other approved agents in treating peptic ulcer disease (i.e., PPIs tend to control symptoms and
heal ulcers more rapidly than other antiulcer drugs). PPIs provide effective healing of duodenal
ulcers; healing rates at 4 weeks are similar to those reported for H2-receptor antagonist therapy at 8
weeks.
2. All PPIs are effective in healing erosive esophagitis, provide more rapid symptom relief and more
consistent healing than H2-receptor antagonists, and are also effective in maintenance of healing of
erosive esophagitis.
3. All PPIs except dexlansoprazole and pantoprazole have been approved in various combinations of
antibiotics for the eradication of H. pylori.
4. PPIs have resulted in significant improvement in patients with pathological hypersecretory conditions
(e.g., Zollinger–Ellison syndrome) and GERD compared to H2-receptorantagonists.
5. Esomeprazole and lansoprazole have been approved by the FDA for healing and risk reduction of
NSAID-induced gastric ulcers.
6. Esomeprazole, omeprazole and lansoprazole have been approved by the FDA for use in infants and
children for the short-term treatment of GERD and erosive esophagitis. Omeprazole is approved for
use in children ages 1 to 16 years, and both esomeprazole and lansoprazole are approved for use in
children 1 to 11 years old.
B. ADMINISTRATION AND DOSAGE
1. PPIs are more potent than H2-blockers. In the usual dosage (omeprazole 20 mg daily), these agents
inhibit  90% of 24-hr acid secretion in most patients, rarely producing achlorhydria. Esomeprazole
40 mg daily provided significantly higher intragastric pH values above 4 during 24-hr monitoring
compared to lansoprazole 30 mg, rabeprazole 20 mg, omeprazole 20 mg, and pantoprazole 40 mg.
2. PPIs should optimally be taken in the morning 30 to 60 mins before eating; food activates parietal
cells, maximizing the effect of the PPI. Optimal binding to proton pumps occurs when the pumps are
actively secreting.
3. Recommended adult dosages
a. Erosive esophagitis initially is healed with 20 mg omeprazole or equivalent doses of other PPIs
for 8 to 12 weeks; only omeprazole has a demonstrated dose response in GERD patients
(patients failing omeprazole 20 mg daily may benefit from higher doses; this has not been
demonstrated with esomeprazole, lansoprazole, rabeprazole, or pantoprazole). In addition,
esomeprazole 40 mg every day has been shown to produce significantly higher healing rates
than omeprazole 20 mg or lansoprazole 30 mg across all grades of erosive esophagitis.
b. Dexlansoprazole 30 mg, esomeprazole 20 to 40 mg, lansoprazole 30 mg, omeprazole 20
mg, rabeprazole 20 mg, and pantoprazole 40 mg may be used to manage GERD symptoms in
patients who have failed previous therapy with H2-receptor antagonist therapy.
c. Th e recommended dosage to maintain healing of erosive esophagitis is dexlansoprazole 30
mg, esomeprazole 20 mg, omeprazole 20 mg, lansoprazole 15 mg, pantoprazole 40 mg, or
rabeprazole 20 mg daily for as long as medically necessary.
d. Duodenal ulcer healing requires omeprazole 20 mg, lansoprazole 15 mg, or rabeprazole 20 mg
once daily. Most patients heal within 4 weeks.
4. Esomeprazole, lansoprazole, and omeprazole are delayed-release capsules, and should be taken
before eating, can be used concomitantly with antacids, and should not be chewed or crushed.
Capsule contents can be sprinkled on foods (i.e., applesauce) or mixed with acidic juices.
Suspensions of omeprazole or lansoprazole in sodium bicarbonate have been used for administration
to patients with nasogastric and jejunostomy tubes.
5. Rabeprazole and pantoprazole are available as enteric-coated tablets that should not be crushed or
chewed.
6. Lansoprazole is available as the first orally disintegrating tablet formulation. It is placed on the
tongue, with or without water, until dissolved. However, it needs to be swallowed to be absorbed.
7. Dexlansoprazole is the first and only PPI available as a dual delayed-release capsule
formulation.
8. Omeprazole in sodium bicarbonate powder for suspension (Zegerid) is the first PPI approved by the
FDA for reduction in the risk of upper GI bleeding in critically ill patients. It has a peach/mint flavor
that is tolerable. It is dosed at 40 mg every 6 hrs times two doses (as a loading dose), then 40 mg
daily.
9. Omeprazole (20 mg daily) and lansoprazole (15 mg daily) are approved for the over-the-
counter use of heartburn.
10. No dosing adjustments are necessary in patients with impaired renal or hepatic function or in the
elderly.
11. Intravenous pantoprazole is indicated for management of erosive esophagitis and treatment of
Zollinger–Ellison syndrome. Esomeprazole, lansoprazole, and pantoprazole are currently being widely
used for the treatment of acute bleeding gastric ulcers, though not FDA approved.
12. Intravenous esomeprazole (20 to 40 mg daily), lansoprazole (30 mg daily), and pantoprazole (40 mg
daily) are FDA approved for the short-term use in patients with GERD with a history of erosive
esophagus unable to take oral medications.
13. In patients with nocturnal signs and symptoms of GERD, twice daily PPIs have been effective when
taken appropriately. Th e addition of an H2RA to the twice-daily PPI has shown little added benefit
and is not recommended.
C. PRECAUTIONS AND MONITORING EFFECTS
1. Headache, diarrhea, abdominal pain, nausea and vomiting, and flatulence have been reported in
1% of patients.
2. Fever, fatigue, malaise, elevated liver enzymes, dizziness, vertigo, skin rash, and itching have been
reported in < 1% of patients.
D. SIGNIFICANT INTERACTIONS
1. Omeprazole interferes with the hepatic microsomal enzyme metabolism (cytochrome P450) of
diazepam, warfarin, and phenytoin, although clinically significant interactions are
infrequent.
2. PPIs may decrease the antiplatelet activity of clopidogrel but the exact clinical
significance is still unclear.
3. Because gastric pH plays a role in the bioavailability of ketoconazole, ampicillin esters, and iron
salts, prolonged gastric acid inhibition with PPIs may decrease the absorption of these agents.
4. Antacids may be used concomitantly with all PPIs.
5. Food may reduce the bioavailability of esomeprazole and lansoprazole by 50%; food does not reduce
the bioavailability of omeprazole or rabeprazole.

7. BISMUTH COMPOUNDS
In the United States, bismuth subsalicylate (Pepto-Bismol) is the only available bismuth product.
A. MECHANISM OF ACTION
Bismuth prevents adhesion of H. pylori to gastric mucosa, decreases resistance when used with other
anti–H. pylori agents, inhibits release of proteolytic enzymes, and suppresses H. pylori growth.
B. ADMINISTRATION AND DOSAGE
1. Bismuth subsalicylate is highly effective when combined with PPIs and/or antibiotics. Eradication
rates with these combinations are  80%.
2. Preferred regimen with bismuth: bismuth subsalicylate 525 mg four times a day, metronidazole 250
mg four times a day, tetracycline 500 mg four times a day plus PPI (omeprazole 20 mg every day or
lansoprazole 30 mg every day) for 2 weeks total. Th is regimen provides consistently high eradication
rates (90%), and may be useful for patients who have failed previous therapy. Th is regimen is not
currently FDA approved.
C. PRECAUTIONS AND MONITORING EFFECTS
1. CNS toxicity with higher doses, including neurotoxicity
2. Tinnitus, hyperpyrexia, tachycardia, and confusion (salicylism) from high doses of bismuth
subsalicylate

8. SEDATIVES
They are useful adjuncts in promoting rest for highly anxious ulcer patients.

B. OTHER THERAPEUTIC MEASURES

1. MODIFICATION OF DIET AND SOCIAL HABITS
a. Previously emphasized in ulcer therapy, strict dietary limitations now are considered largely
unnecessary.
i. Bland or milk-based diets formerly were recommended; however, research indicates that
these diets do not speed ulcer healing. In fact, most experts now advise ulcer patients to
avoid milk because recent studies show that milk increases gastric acid secretion. Also,
because milk leaves the stomach quickly, it lacks an extended buffering action.
ii. Small, frequent meals, also previously recommended, can worsen ulcer pain by causing acid
rebound 2 to 4 hrs after eating.
b. Current dietary guidelines emphasize avoiding foods and beverages known to exacerbate
gastric discomfort or promote acid secretion. This category typically includes coffee, caffeinated
beverages, and alcohol.
c. Smoking. Patients who smoke should be encouraged to quit because smoking markedly slows
ulcer healing, even during optimal ulcer therapy.
d. NSAIDs should be avoided by ulcer patients.
2. SURGERY
An ulcer patient who develops complications may require surgery—sometimes on an emergency basis.
Incapacitating recurrent ulcers also may warrant surgery.
a. Types of surgical procedures for ulcer disease include antrectomy and truncal vagotomy
(Billroth I procedure), partial gastrectomy and truncal vagotomy (Billroth II procedure), highly
selective (proximal gastric) vagotomy, and total gastrectomy (the treatment of choice for
Zollinger–Ellison syndrome that is unresponsive to medical management).
i. A vagotomy severs a branch of the vagus nerve, thereby decreasing HCl secretion.
ii. An antrectomy, by removing the antrum, eliminates some acid-secreting mucosa as
well as the major source of gastrin.
b. The general indications for antireflux surgery are failure of medical therapy to heal or prevent
relapse of erosive esophagitis, inability of medical therapy to prevent recurrence of stricture, or a
patient whose lifestyle is adversely affected by the need for medical therapy. Laparoscopic
fundoplication is currently the gold standard for GERD, and successfully relieves symptoms and
heals lesions in approximately 85% of patients. However, recent studies have demonstrated that
most patients require continued medical therapy aft er fundoplication.

3. EMERGING ENDOSCOPIC THERAPIES

Three endoscopic techniques to treat GERD have recently been introduced.
a. Augmentation of LES pressure may be achieved by delivery of radio frequency energy to the
muscle of the gastroesophageal junction (Stretta procedure). Th e radio frequency is delivered by
means of a flexible catheter made up of a bougie tip, a balloon-basket combination, and four-
needle delivery sheaths.
b. Another endoscopic procedure, the EndoCinch, augments the LES by suturing of the mucosa.
c. The third endoscopic/endoluminal treatment is by use of Enteryx injection.
d. Early studies have demonstrated good feasibility in performing these procedures, and an overall
satisfactory safety profile. Further studies are necessary to assess long-term failure rate, early
versus late complications, and success rate in the different GERD groups.