Gastroesophageal Reflux Disease
(GERD)

:Definitions
Gastroesophageal Reflux (GER): Escape of gastric
contents into the esophagus. This process may or may
not produce symptoms.
Reflux esophagitis: Esophageal inflammation caused
by the refluxed material.
Gastroesophageal Reflux Disease (GERD): Any
symptomatic condition or anatomic alteration caused by
the reflux of noxious material from the stomach into the
esophagus.

Gastroesophageal reflux disease occurs when the
amount of gastric juice that refluxes into the
esophagus exceeds the normal limit, causing
symptoms with or without associated esophageal
mucosal injury i.e., esophagitis

PATHOPHYSIOLOGY OF GERD
A) Dysfunctional Lower Esophageal Sphincter
B) Gastric Factors
C) Impaired Esophageal Clearance

A) Dysfunctional Lower Esophageal
Sphincter (LES)
• The LES is a 1-3.5 cm segment of specialized
circular muscle in the wall of the distal esophagus.
• It maintains a resting pressure of 10-45 mmHg higher
than that of the stomach.

Types of LES dysfunction
• Intrinsic weakness of the LES muscle: Occurs when
the resting pressure in the LES remains at or near 0.
Responsible for > 25% of reflux episodes in patients
with severe GERD.
• Inadequate LES response to increased abdominal
pressure: Increased abdominal pressure could be
caused by inspiration or bending over.

• Transient LES relaxation (TLESR): Normally, the
LES relaxes for 3-10 seconds to allow the
swallowed bolus to enter the stomach. TLESR lasts
for up to 45 seconds and is responsible for 70% of
reflux episodes in patients with severe GERD.
Incompetent LES

B) Gastric Factors:
• Irritant potency of the refluxed material: Esophageal
injury occurs when the refluxed material is caustic to
the esophageal mucosa. Caustic agents that can be
found in the stomach include acid, pepsin, bile &
pancreatic enzymes.

• Delayed gastric emptying: It causes gastric distention
that can stimulate gastric acid secretion & trigger
TLESR.
• Causes:
I. Pyloric channel or duodenal ulcers.
II. Mechanical obstruction e.g. by tumor.
III. Neuromuscular abnormalities e.g. DM, collagen
vascular diseases, hypothyroidism, etc.

C) Impaired Esophageal Clearance
Impaired esophageal clearance can occur in:
Sleep: due to
I. Elimination of the effect of gravity.
II. Salivation & swallowing cease during sleep “no
peristalsis due to absent swallowing”.
Scleroderma: due to impaired peristalsis.
Cigarette smoking: due to decreased salivation.
Hiatus hernia.

ETIOLOGY
A functional (frequent transient LES relaxation) or
mechanical (hypotensive LES) problem of the LES
is the most common cause of GERD.
Transient relaxation of the LES can be caused by:
• Food (coffee, alcohol, chocolate, fatty meals)
• Medications (beta-agonists, nitrates, CCBs, BDZ,
anticholinergics)
• Hormones (e.g. progesterone)

RISK FACTORS
• Black pepper, garlic, raw onions, and other spicy foods
• Chocolate and High fatty food
• Citrus fruits and products, such as lemons, oranges,
and orange juice
• Coffee and caffeinated drinks, including tea and soda
• Tobacco smoking
• Pregnancy
• Obesity and weight gain
• Wearing tight clothing, lying flat after a meal

CLINICAL PRESENTATION
Esophageal symptoms
• Heartburn
• Nausea
• Regurgitation: Reflux of bitter material into the
mouth, usually at night or when bending down.
• Dysphagia: Difficulty in swallowing. Usually
indicates narrowing or stricture of the esophagus. It
may occur due to inflammation & edema.
• Waterbrash: Filling of the mouth suddenly with
saliva. It’s due to reflex salivary secretion
stimulated by acid in the esophagus.

Esophageal symptoms cont’d
• Belching
• Odynophagia: Pain on swallowing. It suggests
the presence of esophageal ulceration.
• Epigastric pain
• Hemorrhage

Extraesophageal symptoms
• Coughing and/or wheezing
• Hoarseness, sore throat
• Otitis media
• Noncardiac chest pain
• Enamel erosion or other dental manifestations

Diagnostic tests
I. Endoscopic examinations
II. Barium swallow
III. Ambulatory monitoring of esophageal pH

COMPLICATIONS OF GERD
• Inflammation of the esophagus (increased risk of
cancer from chronic inflammation)
• Narrowing of the esophagus: strictures
• Lung problems: asthma, pneumonia, voice
changes, wheezing, fluid in the lungs
• Barrett’s esophagus: the lining of the esophagus
is replaced with a similar lining that makes up the
intestinal lining which increases the risk of cancer.

MANAGEMENT OF GERD
The goals are:
• to control symptoms
• to heal esophagitis
• to prevent recurrent esophagitis or other
complications.
The treatment is based on lifestyle modifications and
control of gastric acid secretion through medical
therapy with antacids or proton pump inhibitors or
surgical treatment with corrective antireflux surgery.

LIFESTYLE MODIFICATIONS
• Losing weight (if overweight)
• Avoiding alcohol, chocolate, citrus juice, and tomato-
based products
• Avoiding peppermint, coffee, and possibly the onion
family
• Eating small, frequent meals rather than large meals
• Waiting 3 hours after a meal to lie down
• Refraining from ingesting food (except liquids) within 3
hours of bedtime
• Elevating the head of the bed by 8 inches

LIFESTYLE MODIFICATIONS CONT’D
• Avoiding bending or stooping positions
• Cessation of smoking.
• Foods to eat:
i. Whole grain e.g. cereals, oats
ii. Dry fruits like dates, apricots, figs, raisins
iii. Alkaline fruits like bananas
iv. Non-peppery soups
v. Smoothies

PHARMACOLOGICAL MANAGEMENT
1. H2 receptor antagonists
• These are the first-line agents for patients with mild
to moderate symptoms and grades I-II esophagitis.
• They block the action of histamine. When
histamine is released it causes the parietal cells
to release HCL but this response will be blocked
so gastric acid secretion will be decreased.
• Examples: Ranitidine ,Cimetidine, Famotidine,
Nizatidine.

Drug Duration
Cimetidine
Indication
- Erosive esophagitis diagnosed
by endoscopy.
- 12 w
Famotidine
Dose
- 800 mg BDS
or 400 mg
QDS
- 20 mg BDS -6 w
- 20-40 mg - 12 w
BDS
Nizatidine
- Short term ttt of symptoms.
-Esophagitis due to GERD
including erosive or ulcerative
disease diagnosed by endoscopy
-Esophagitis due to GERD.
including erosive or ulcerative
disease & associated heartburn.
- 150 mg BDS - 12 w
Ranitidine - Treatment of symptoms.
-Esophagitis due to GERD
including erosive or ulcerative
disease diagnosed by endoscopy
-150 mg BDS
- 150 mg QDS
No
limit
specifi
ed

PHARMACOLOGICAL MANAGEMENT
2. Proton Pump Inhibitors (PPIs)
• Attach to the “proton pump” on the parietal cells which
is the hydrogen/potassium (H+, K+) ATPase enzyme
and blocks the release of hydrogen ions. These ions
would mixed with the chloride ions and form gastric
acid but this is blocked so there is a decrease in
gastric acid.
• PPIs are effective in control of symptoms & signs of
GERD, heal erosive esophagitis & diminish formation
of esophageal strictures.

• PPIs improves dysphagia & decrease the need for
esophageal dilatation in patients who have
esophageal strictures.
• PPIs are effective if taken 15-30 minutes before
breakfast or dinner.
Drugs of this group include:
Omeprazole 20 mg – 40 mg.
Lansoprazole15 mg – 30 mg.
Rabeprazole 20 mg.
Pantoprazole 20 mg – 40 mg.
Esomeprazole 20 mg – 40 mg.
Omeprazole NaHCO3 20 mg – 40 mg.

PHARMACOLOGICAL MANAGEMENT
3. Antacids
• Antacids may be aluminum, magnesium, or
calcium based. Antacids neutralize the acid in
the stomach so that there is no acid to reflux.
• They are emptied from the empty stomach
quickly so they should be given an hour after
meal to prolong their duration of action.
• Effective in controlling mild symptoms of GERD.

PHARMACOLOGICAL MANAGEMENT
4. Prokinetic Drugs
These agents act by:
a) Increasing LES pressure.
b) Enhancing gastric & esophageal emptying.
Examples:
Metoclopramide HCl.
Domperidone.
Mosapride citrate.

-Metoclopramide HCl: Dopamine antagonist, centrally
acting antiemetic. Its effective in treatment of mild
disease. It crosses BBB so, it has many central side
effects.
Side effects: Agitation, restlessness, somnolence,
anxiety, insomnia, extrapyramidal manifestations &
galactorrhea.
-Domperidone: Dopamine antagonist & produce effects
similar to metoclopramide. Unlike metoclopramide it
doesn’t cross BBB so there is no central side effects.

- Mosapride citrate: 5-HT4 receptor agonist & partial 5-
HT3 antagonist. Unlike cisapride it doesn’t block K+
channels so no cardiac toxicity will occur, also doesn’t
block D2 receptors, so there are no extrapyramidal
manifestations.

PHARMACOLOGICAL MANAGEMENT
5. Sucralfate
An aluminum sucrose polysulfate. Effective in treatment
of mild reflux esophagitis. It’s efficacy is comparable to
that of H2 blockers.

SURGICAL MANAGEMENT
There are several different antireflux operations (e.g.
Nissen, Belesy, Toupet fundoplication). The most
popular is Nissen fundoplication (open or laparoscopic).
Nissen fundoplication: The gastric fundus (upper part)
of the stomach is wrapped around the lower end of the
esophagus and stitched in place, reinforcing the closing
function of the lower esophageal sphincter.

SAMPLE CASE STUDIES
1. A 54 year old male patient walked into your
pharmacy with a complaint of intermittent chest pain
with substernal burning that radiates to his mid-back.
He describes the pain as stabbing. He states that the
symptoms occur after he has eaten a large meal and
in the middle of the night, which often wakes him
from his sleep.
He awakes with shortness of breath, coughing, and a
bitter taste in his mouth. He keeps antacids with him
at all times to help with the symptoms.

SAMPLE CASE STUDIES
• Based on the information you have already received
what other history is essential for you to gather from
the patient?
• How do you manage the patient?

SAMPLE CASE STUDIES
2. MC, a 20-year-old Muslim man, came into your
Pharmacy on day 20 of Ramadan fasting to complain of
loss of appetite and occasional lower sternal chest pain
30-60 minutes after meals. He says that symptoms
began about 8 weeks ago. MC is 5ft, 10 inches tall, and
weighs 92kg. Besides chest pain after meals, MC
complains of heartburn several times a week and
occasionally brings up bitter liquid into his mouth.
On further inquiries, he opens up on the fact that he was
placed on a new medication 4 weeks ago but stopped
taking his medications when Ramadan started.

SAMPLE CASE STUDIES
• What other information will you be requiring from
MC?
• How will you manage MC as a Pharmacist?