This document provides an overview of gastroesophageal reflux disease (GERD), including its pathophysiology, symptoms, complications, diagnosis, and treatment strategies. It defines GERD and distinguishes between NERD and ERD. Diagnosis is based on symptoms, though endoscopy may be used for alarm symptoms or treatment failure. Treatment involves lifestyle changes, antacids, H2 blockers, proton pump inhibitors, and sometimes promotility or surgical options. The goal of treatment is symptom relief and prevention of complications like Barrett's esophagus.

1. Pathophysiology and Therapeutics
Gastroesophageal Reflux Disease
(GERD)
Israel Sefah (FPCPharm)
9/27/2023 1

2. Case study
9/27/2023 2

3. Outline
• Learning objectives
• Introduction
• Symptoms
• Long term complications
• Diagnosis
• Treatment strategies
• Cases
• Reference
9/27/2023 3

4. Learning objectives
• Review International guidelines
• Discuss diagnosis criteria
• Recommend appropriate therapy
• Apply knowledge to solve clinical cases
9/27/2023 4

5. Introduction - WGO 2015 Guidelines
• GERD is defined as troublesome symptoms
sufficient to impair an individual’s quality of life,
• or injury or complications that result from the
retrograde flow of gastric contents into the
esophagus, oropharynx, and/or respiratory tract.
• “PPI trial.” 1-2 weeks of empirical short to ascertain
if patience symptoms is acid related is no longer
recommended
• A formal course of PPI therapy, of adequate duration
(usually 8 weeks) is required in order to assess the
treatment response in GERD patients
9/27/2023 5

6. GERD Diagnosis (ACG 2013 Guideline)
• A presumptive diagnosis of GERD can be
established in the setting of typical symptoms
of heartburn and regurgitation.
• Empiric medical therapy with PPI is
recommended in this setting
9/27/2023 6

7. Introduction - ACG 2013 Guideline
• A formal course of PPI therapy, of adequate
duration (usually 8 weeks) is required in order
to assess the treatment response in GERD
patients
• Endoscopy is particularly recommended for
patients with alarm features
9/27/2023 7

8. Introduction
• GERD is a common medical disorder.
• GERD is defined by consensus
• It is defined as symptoms or complications
resulting from refluxed stomach contents into the
esophagus or beyond, into the oral cavity
(including the larynx) or lung
• Episodic heartburn that is not frequent enough or
painful enough to be considered bothersome by
the patient is not included in this definition of
GERD.
9/27/2023
8

9. Introduction - Pathophysiology
• The key factor is abnormal reflux of gastric
contents
• GERD is associated with defective lower
esophageal sphincter leading to:
– spontaneous transient LES relaxations
– transient increases in intra-abdominal
pressure
– an atonic LES, all of which may lead to the
development of GERD
9/27/2023 9

10. Introduction - Pathophysiology
• Dysfunctional defense mechanism may also
contribute such as:
– abnormal esophageal anatomy: Hiatal hernia
– improper esophageal clearance of gastric fluids
– reduced mucosal resistance to acid
– delayed or ineffective gastric emptying and
intra-abdominal pressure
– and reduced salivary buffering of acid
9/27/2023 10

11. • Refluxates that may promote esophageal
damage on reflux into the esophagus include:
– gastric acid
– pepsin
– bile acids
– and pancreatic enzymes
9/27/2023 11

12. Introduction - GERD Subtypes
• Symptoms without erosions on endoscopy
(nonerosive reflux disease - NERD)
• Symptoms with erosions on endoscopy
(erosive reflux disease -ERD)
9/27/2023 12

13. Symptoms -1
• Typical symptoms:
– Heartburn (pyrosis)
– Dypepsia
– Water-brash
– Regurgitation
• Alarm symptoms
– These symptoms warrant immediate referral
for more invasive testing.
• Extra-esophageal or atypical symptoms
9/27/2023 13

14. Symptoms -2
• Spectrum of injury starts with no erosion to
esophagitis, erosive esophagitis (erosion of
squamous epithelium) to complicated forms
• Most patients do not progress to erosive
esophagitis
9/27/2023 14

15. Extraesophageal or atypical symptom
• Chronic cough
• asthma-like symptoms
• recurrent sore throat, laryngitis or hoarseness
• dental enamel loss
• noncardiac chest pain
• sinusitis, pneumonia, bronchitis, and otitis media
(less common atypical symptoms)
• Atypical symptoms require referral for addtitional
testing
9/27/2023 15

16. Alarm symptoms
• Dysphagia: difficulty with swallowing
• Odynophagia: pain with swallowing
• Bleeding
• Weight loss
• Hematemesis
• Melena
• Chest pain
• Epigastric mass
• These symptoms warrant immediate referral for
more invasive testing (endoscopy)
9/27/2023 16

17. Aggravating factors
• Recumbency (gravity)
• Elevated intra-abdominal pressure
• Reduced gastric motility (e.g., gastroparesis)
• Decreased lower esophageal sphincter (LES)
tone (e.g., peppermint, caffeine, nicotine)
• Direct mucosal irritation (e.g., irritating foods,
bisphosphonates, NSAIDs).
9/27/2023 17

18. Long-term complications
• Esophageal erosion
• Strictures
• Obstruction
• Barrett esophagus
replacement of squamous epithelial cells with
columnar epithelial cells within the lower
esophagus
Results in increased risk of esophageal
carcinoma
9/27/2023 18

19. Diagnosis - Symptom
• A presumptive diagnosis of GERD is made
when typical symptoms of heartburn and
regurgitation are present
• Empiric therapy with a proton pump inhibitor
(PPI) is recommended if patient has typical
symptoms of heartburn or regurgitation.
9/27/2023 19

20. Diagnosis -Symptom
• Screening for H. pylori is not recommended.
H. pylori screening is only recommended in
patients with PUD, a history of a documented
peptic ulcer, or gastric mucosa-associated
lymphoid tissue lymphoma (MALT)
• Patients with noncardiac chest pain that is
suspected of having been caused by GERD should
have a diagnostic evaluation before institution of
therapy
9/27/2023 20

21. Diagnosis - Endoscopy
• Upper endoscopy is not necessary in the
presence of typical GERD symptoms.
• Endoscopy is recommended in the presence
of alarm symptoms and in the screening of
patients at high risk of complications.
• Repeat endoscopy is not indicated in patients
without Barrett esophagus in the absence of
new symptoms
9/27/2023 21

22. Diagnosis - Ambulatory pH testing
• Ambulatory esophageal reflux monitoring is
indicated before considering endoscopic or
surgical therapy in patients with NERD (or unclear
diagnosis)
• This should be part of the evaluation of patients
who are refractory to PPI therapy and in situations
when the diagnosis of GERD is in question.
• Ambulatory reflux monitoring is the only test that
can assess reflux symptom association.
9/27/2023 22

23. Management of GERD
9/27/2023 23

24. Case
A 52-year-old Man with Burning Sensation in His Chest
9/27/2023 24

25. Treatment Strategies – Non-pharmacological
• Non-pharmacologic interventions and lifestyle
modifications are unlikely to control symptoms
in most patients
• The American Gastroenterological Association
(AGA) guidelines cite insufficient evidence to
advocate lifestyle modifications for all patients
• AGA advocate this for use in targeted
populations
9/27/2023 25

26. Treatment Strategies – Non-pharmacological
• Dietary modifications in patients whose
symptoms are associated with certain foods or
drinks
• Avoid aggravating foods and beverages
Reduce LES pressure (alcohol, caffeine,
chocolate, citrus juices, garlic, onions,
peppermint or spearmint)
Direct irritation (spicy foods, tomato juice,
or coffee).
9/27/2023 26

27. • Reduce fat intake (high-fat meals slow gastric
emptying) and portion size
• Avoid eating 2–3 hours before bedtime
• Remain upright for two hours after meals
• Weight loss if overweight or recent weight gain
• Reduce or discontinue nicotine use in patients
who use tobacco products (affects LES).
• Elevate head of bed and avoid meals 2–3 hours
before bedtime if nocturnal symptoms.
9/27/2023 27

28. • Avoid tight-fitting clothing (decreases intra-
abdominal pressure).
• Avoid medications that may:
Reduce LES pressure (α-adrenergic antagonists,
calcium channel blockers, anticholinergics,
theophylline, benzodiazepines, opiates)
Delay gastric emptying (opiates, tricyclic
antidepressants, calcium channel blockers,
progesterone)
Direct irritation (NSAIDs, aspirin,
corticosteroids).
9/27/2023 28

29. Pharmacologic therapies
• Initial treatment depends on the severity,
frequency, and duration of symptoms
• “Step-down” treatment: Starting with maximal
therapy, such as therapeutic doses of PPIs
Is always appropriate as a first-line strategy in
patients with documented esophageal erosion.
Advantages: Rapid symptom relief, avoidance
of over-investigation
 Disadvantages: Potential overtreatment,
higher drug cost, increased potential for
adverse effects
9/27/2023 29

30. • “Step-up” treatment: Starting with lower-dose
over-the-counter (OTC) products
Its appropriate for patients with less severe
symptoms without evidence of esophageal
erosion.
Advantages: Avoids overtreatment, has lower
initial drug cost.
Disadvantages: Potential under-treatment
(partial symptom relief; may take longer for
symptom control; may lead to over-
investigation)
9/27/2023 30

31. • Treatment duration of at least 4 weeks if
NERD
• 8 weeks if ERD.
• Maintenance therapy should be used if
symptoms recur or complications are present
9/27/2023 31

32. AGA Guideline Recommendation
9/27/2023 32

33. STG - 2017
• NERD – Antacid or PPI daily for 4 – 8 weeks
• Severe or Erosive GERD – PPI standard dose
/double dose for 8 weeks
• Severe or Erosive GERD (with bloating) – Use
drugs for ERD + Promotility (6 – 8hrly)
9/27/2023 33

34. Pharmacologic agents - Antacids
• Calcium-, aluminum-, and magnesium-based
products are available OTC in a wide variety of
formulations (capsules, tablets, chewable
tablets, and suspensions).
– Neutralizing acid and raising intragastric pH
– Results in decreased activation of
pepsinogen and increased LES pressure
– Rapid onset of action but short duration,
necessitating frequent dosing
9/27/2023 34

35. Antacids
• Some products (Gaviscon) also contain the
antirefluxant alginic acid.
• Alginic acid which forms a viscous layer on top of
gastric contents to act as a barrier to reflux
• Use antacid as first-line therapy for:
– intermittent (less than twice weekly) symptoms or
– as breakthrough therapy for those on PPI/H2RA
therapy
• Antacids are not appropriate for healing established
esophageal erosions
9/27/2023 35

36. Antacids
• Adverse reactions:
Constipation (aluminum)
Diarrhea (magnesium)
Accumulation of aluminum and magnesium in
renal disease with repeated dosing
• Drug interactions:
Chelation (fluoroquinolones, tetracyclines)
 reduced absorption owing to increases in pH
(ketoconazole, itraconazole, iron, atazanavir,
delavirdine, indinavir, nelfinavir)
9/27/2023 36

37. Pharmacologic agents – H2RAs
• Reversibly inhibit histamine-2 receptors on the
parietal cell
• Prolonged use is associated with the
development of tolerance and reduced efficacy
(tachyphylaxis).
• Therapy with H2RAs is less efficacious than
therapy with PPIs in healing erosive
esophagitis
9/27/2023 37

38. 9/27/2023 38

39. Pharmacologic agents – PPIs
• Irreversibly inhibit the final step in gastric acid
secretion; greater degree of acid suppression
achieved and typically longer duration of action
than H2RAs
• Most effective agents for short- and long-term
management of GERD and for management of
erosive disease
• Most effective when taken orally 30 -60 minutes
before meals; for divided dosing, give evening
dose before evening meal instead of at bedtime.
9/27/2023 39

40. 9/27/2023 40

41. 9/27/2023 41

42. Promotility agents
• The 2013 guidelines state that therapy for
GERD other than acid suppression, including
prokinetic therapy or baclofen, should not be
used in patients with GERD without diagnostic
evaluation
• These agents work through cholinergic
mechanisms to facilitate increased gastric
emptying
9/27/2023 42

43. Promitility agent - Metoclopramide
• Dopamine antagonist
• Must be dosed several times a day
• Associated with many adverse effects such as
dizziness, fatigue, somnolence, drowsiness,
extrapyramidal symptoms (EPS), and
hyperprolactinemia.
• Indications for GERD and diabetic gastroparesis
• Combination with PPI offers modest improvement
9/27/2023 43

44. Promitility agent - Bethanechol
• Cholinergic agonist
• Poorly tolerated because of adverse effects
such as diarrhea, blurred vision, and
abdominal cramping
• May also increase gastric acid production
9/27/2023 44

45. Promitility agent - Cisapride
• Available only on a restricted basis for patients
whose other therapies have failed
• Cisapride was withdrawn from the market
initially because of cardiac arrhythmia
(torsades de pointes) when used in
combination with drugs inhibiting CYP3A4.
9/27/2023 45

46. Mucosal protectants
• Sucralfate has a limited role in the treatment
of GERD.
9/27/2023 46

47. Surgical therapy
• Surgical therapy (laparoscopic Nissen fundoplication) is
a treatment option for long-term therapy in patients
with GERD.
• Surgical therapy is generally not recommended in
patients who do not respond to PPI therapy.
• Surgical therapy is as effective as medical therapy for
carefully selected patients with chronic GERD when
performed by an experienced surgeon.
• Patients with obesity contemplating surgical therapy
for GERD should be considered for bariatric surgery.
• Gastric bypass would be the preferred operation in
these patients.
•
9/27/2023 47

48. 9/27/2023 48

49. Case
44-year-old Woman Presents for Follow-up of GERD
9/27/2023 49

50. References
• American Gastroenterological Association
Institute. 2013 Guideline for the diagnosis and
management of gastroesophageal reflux disease.
• Haag S, Andrews JM, Katelaris PH, et al.
Management of reflux symptoms with over-the
counter proton pump inhibitors: issues and
proposed guidelines. Digestion 2009;80:226-34.
• Pharmacotherapy by Dipiro et al, 10th Edition
9/27/2023 50