1 GASTRO ESOPHAGEAL REFLUX DISEASE (GERD)

Mulat B.
 Objectives
2

At the end of this session, you will be able to:

 Define GERD, describe its pathophysiology, and

epidemiology
 Describe the clinical features of GERD

 Describe the consequence of GERD

 Describe the diagnostic work up of GERD

 Explain the general principle of GERD treatment

 Definition
3

 In general terms, gastroesophageal reflux disease

(GERD) is symptoms or complications
resulting from refluxed stomach contents
into
 the esophagus or
 beyond, into the oral cavity (including the
larynx) or lung.
 Definition…
4

 Reflux esophagitis describes a subset of

patients with symptoms of GERD who also
have endoscopic or histopathologic evidence
of esophageal inflammation.
 Essentials of diagnosis
5

 Most common symptoms - Heartburn,

regurgitation, and dysphagia
 “Alarm signs”– dysphagia, odynophagia,

weight loss, family history of upper GI tract

cancers, persistent nausea and emesis, long
duration symptoms (>10 years), and incomplete
response to treatment
 Atypical manifestations (e.g., bronchospasm,

laryngitis and chronic cough) are common

 Definition…
6

 Transient inappropriate relaxation of the lower

esophageal sphincter (LES) is the predominant
pathophysiologic mechanism in the majority
of GERD patients
 Gastroparesis and a reduced LES pressure

play a significant role in patients with

moderate to severe disease
 Definition….
7

 Symptom-based esophageal GERD syndromes

 May exist with or with out esophageal injury
 most commonly present as heartburn, regurgitation or dysphagia
 Less commonly, odynophagia (painful swallowing) or
hypersalivation
 Tissue injury–based syndromes
 may exist with or without symptoms
 The spectrum of injury includes
 Esophagitis : inflammation of the lining of the esophagus
 Barrett esophagus : when tissue lining the esophagus is
replaced by tissue similar to the lining of the intestine
 Strictures, and esophageal adenocarcinoma
 Epidemiology
8

 GERD occurs in people of all ages

 Most common in those older than age 40 years
 No major difference b/n men and women except
during pregnancy
 Important risk factors and co morbid conditions
 Family history, obesity, smoking, alcohol
consumption, certain medications and foods,
respiratory diseases
 Foods and Medications That May Worsen GERD
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Foods Medications
 Fatty meal  Anticholinergics , Ethanol

 Barbiturates ,Nicotine
 Garlic
(smoking)
 Carminatives
 Caffeine , Nitrates
(peppermint, spearmint)
 Dihydropyridine calcium
 Onions
channel blockers
 Chocolate
 Estrogen, progesterone

 Chili peppers  Dopamine, Tetracycline

 Coffee, cola, tea  Theophylline

 Direct irritants to the esophageal mucosa
10

Foods Medications
 Spicy foods  Aspirin

 Tomato juice  Iron

 Orange juice  Quinidine

 Coffee  NSAIDs

 Potassium chloride
 Pathophysiology
11

 Key factor for GERD dev’t:

 abnormal reflux of gastric contents from the stomach
into the esophagus
 associated with defective lower esophageal sphincter
(LES) pressure or function (some cases)
 Decreased gastroesophageal sphincter pressures
related to
 spontaneous transient LES relaxations,
 transient increases in intraabdominal pressure, or
 an atonic LES
12
 Pathophysiology…
13

 Problems with other normal mucosal

defense mechanisms
 abnormal esophageal anatomy
 improper esophageal clearance of gastric fluids
 reduced mucosal resistance to acid
 delayed or ineffective gastric emptying
 inadequate production of epidermal growth factor,
and
 reduced salivary buffering of acid
 Pathophysiology…
14

 Aggressive factors that damage esophagus up on

reflux:
 Gastric acid, pepsin, bile acids, and pancreatic

enzymes
 Composition and volume of the refluxate, as well as

duration of exposure are important factors that

determine GERD progression
 Rational therapeutic regimens in the treatment of
GERD are designed to
 maximize normal mucosal defense mechanisms and
 attenuate the aggressive factors
 Pathophysiology…
15

 Pregnancy is a condition in which reflux is

common
 hormonal effects on esophageal muscle, LES tone,
and physical factors (increased intraabdominal
pressure) resulting from an enlarging uterus
 The above factors may not always lead to GERD but
need to consider other natural defense mechanisms
 anatomic factors, esophageal clearance, mucosal
resistance, and other gastric factors
 Pathophysiology…
16

 Anatomic Factors
 Patients with hypotensive LES pressures
 Esophageal Clearance
 Production of too much acid but that the acid produced
spends too much time in contact with the esophageal mucosa
 Depends on esophageal clearance
 Cleared by primary peristalsis in response to swallowing
(increasing saliva flow) or secondary peristalsis in response
to esophageal distension and gravitational effects
 Mucosal Resistance
 Problem in esophageal mucosa and submucosa - are mucus-
secreting glands
 Pathophysiology…
17

 Gastric Emptying
 Delayed gastric emptying can contribute to
gastroesophageal reflux
 Factors that increase gastric volume and/or decrease
gastric emptying
 smoking and high-fat meals
 Composition of Refluxate
 composition, pH, and volume of the refluxate are
important aggressive factors
 GERD Long-Term Complications
18

• Esophageal erosion
• Strictures/obstruction
• Barrett’s esophagus
– The lining of mucosa that is soft and smooth is
replaced with rough scar like tissue……….metaplasia
– No symptoms associate with it
– But it is a risk factor of esophageal cancer
– Incidence ……………1%
– Men ………….are affected the most
• Reduce quality of life
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 GERD Diagnosis
21

 Symptom-based
 Presence of pyrosis… or indigestion
 The first or only symptom
 Extra-esophageal symptoms

 Endoscopy
 Treatment
22

Goals:
 Alleviatesymptoms,
 Decrease the frequency of recurrent disease
 Promote healing of mucosal injury, and
 Prevent complications.
 Rx…
23

Therapy is directed at:

 decreasing the acidity of the refluxate;

 Decreasing the gastric volume available to be

refluxed;
 improving gastric emptying;

 increasing LES pressure;

 enhancing esophageal acid clearance; and

 protecting the esophageal mucosa.

Therapeutic interventions in the management of GERD
 Rx…
25

Treatment is categorized into the following

modalities:
✓Phase I: Lifestyle changes and patient-
directed therapy with antacids and/or
nonprescription H2RA or PPIs.
✓Phase II: Pharmacologic interventions with
standard or high-dose acid suppressing agents.
✓Phase III: Interventional therapies (anti-
reflux surgery).
 Rx…
26

 Patients who do not respond to lifestyle modifications

and patient-directed therapy after 2 weeks should seek
medical attention and are generally started on empiric
therapy consisting of an acid-suppression agent
 H -receptor antagonists in divided doses are effective
2
in patients with mild GERD
 Pts presenting with moderate to severe symptoms

(with or without esophageal erosions) should be

started on a PPI as initial therapy because it provides
the most rapid symptomatic relief and healing in the
highest percentage of pts.
 Non-Pharmacological treatment
27

 Dietary modification
 Unlikely to control symptoms fully in all
patients however, avoid foods and drugs that
reduce LES.
 Avoid fat Intake …slow down gastric emptying
 Avoid excessive alcohol…reduce LES
 Meals 2-3 hours before bed
 small but frequent meals
 remain upright after meals
 Head of bed elevation(for nocturnal GERD)
 GERD Non-Pharmacological treatment
28

• Body weight
– excess fat around the belly increases Pressure
• Smoking
– Cough a lot……..increases reflex
– Produce ….50% less saliva which contains
HCO3
– Cause………………slow down healing

• Clothing………….tight cloth
 Pharmacological treatment
29

 Empiric therapy…….recommended if
uncomplicated
 First line drug therapy…………PPI

 Differences among PPI in efficacy………none

 If used in equivalent doses

 Fast acting agents…antacids …but has short
duration
 Drugs to use as a combination……no evidence
 Pharmacological treatment-
Anti acids
30

 Most common – Ca, Al, and Mg based

 All are OTC

 MOA

 Neutralizes acid,
 decrease pepsinogen activity,
 increase LES pressure,
 Rapid onset of action but short duration
 Antacids
31

 ADR…………Constipation, Diarrhea
 Accumulation of Al/Mg in renal patients
 Drug Interactions
 Reduced absorption of drugs which need acidic
environment for absorption….itraconazole,
ketoconazole, iron
 Chelation (Quinolones, TTC)
 Histamine-2 Receptor antagonists
32

 Reversibly inhibit histamine (H2) receptors on

the parietal cell
 H2-receptor antagonists in divided doses are

effective in treating patients with mild to

moderate GERD
 Can be used as…………

 Preventive therapy before meals or exercise

 Less efficacious vs. PPI for erosive esophagitis
33

• The most common adverse effects are headache,

somnolence, fatigue, dizziness, and either constipation
or diarrhea.
• adjust dose in renal disease
• ADR:
- cimetidine (gynecomastia)
– tolerance

• Drug Interactions:
– Cimetidine is an enzyme inhibitor
–warfarin, theophylline, phenytoin, nifedipine, and propranolol
• Reduced absorption (itraconazole, ketoconazole, iron)
34

Non prescription doses/per

day or BID/
Prescription doses
 Cimetidine 200 mg  Cimetidine 400 mg twice
 Famotidine 10 mg daily
 Famotidine 20 mg twice
 Nizatidine 75 mg
daily
 Ranitidine 75 mg  Nizatidine 150 mg twice
daily
 Ranitidine 150 mg twice
daily
 Gynecomastia
35

• Development of abnormally
– large mammary glands in males
resulting in breast enlargement,
which can sometimes cause
secretion of milk.
• Incidence
– 4% with Cimetidine
• Mechanism
– increase production of
prolactine
• Spironolactone
– has a similar effect
 Proton Pump Inhibitors
36

• Inhibit irreversibly at the gastric H+/K+-

ATPase in gastric parietal cells.
– final step in gastric acid secretion
• Greater degree and duration of acid
suppression
• Patients should be instructed to take their
proton pump inhibitor in the morning, 15 to 30
minutes before breakfast, to maximize
efficacy, because these agents inhibit only
actively secreting proton pumps.
37

 Patients with nocturnal symptoms may benefit

from taking their proton pump inhibitor prior
to the evening meal.
 If dosed twice daily, the second dose should

be administered approximately 10 to 12 hours

after the morning dose and prior to a meal or
snack.
38

 Twice daily dosing may also be appropriate

during a diagnostic trial for non cardiac chest
pain, in patients with atypical or complicated
symptoms, and in those with breakthrough
symptoms.
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• Withdrawal from PPIs can lead to severe

rebound acid secretion, a complication that can
force users to become dependent on them

• The proton pump inhibitors are usually well

tolerated; however, potential adverse effects
include headache, dizziness, somnolence,
diarrhea, constipation, nausea, and vitamin B12
deficiency.
 PPI and H2RA Long-Term
Complications
40

 Increased risk of …………..

 community-acquired pneumonia
 Patients at risk……….. Immunocompromised
 the elderly, children, asthmatics or those with COPD
 Increased incidence of hip fracture
 Patient at risk: high dose of PPI or longer duration
 Attributable to reduction of Ca absorption
 Overgrowth of Clostridum Difficle (PPI)
 PPI Drug interactions
41

 PPIs can undermine the effectiveness of

clopidogrel, a heart-protecting medication,
raising the risk of heart attack
 Omeprazole

 has a greater chance of interaction than other PPIs,

such as pantoprazole.
 NOTE
42

• PPIs only inhibit ACTIVE proton pumps, so they ….

– work best when acid secretion is being triggered by a
meal.
• On the other hand, H2-blockers work without
regard to…
– meals...and
– they block acid secretion that's triggered by histamine
at night.
• But developing tolerance is a concern with chronic
H2-blockers.
43

• Have patients take their PPI ……….

– 30 to 60 minutes BEFORE meals so the drug is on board
before the acid pumps are activated.
• For patients taking a PPI once daily…………
– suggest giving it before dinner instead of before breakfast.
– Or try splitting the dose and giving it before breakfast AND
dinner.
• Advise patients ………….
– not to take an H2-blocker and PPI at the same time.
– The H2-blocker can decrease acid secretion and therefore
make the PPI less effective
 Promotility Agent
44

• Metoclopramide, a dopamine antagonist,

increases LES pressure in a dose-related
manner, and accelerates gastric emptying in
gastroesophageal reflux patients.
• Metoclopramide provides symptomatic
improvement for some patients with GERD
• Extrapyramidal effects, sedation, and
irritability are common with metoclopramide.