Prepared by, Dr. Sabareesh Subramanian A PharmD

1. Gastro
Esophageal
Reflux
Disease GERD
Dr. SABAREESH SUBRAMANIANA
PharmD

2. What is GERD ?
• GERD refers to any symptomatic clinical condition or histologic
alteration that results from episodes of gastroesophageal reflux
• Gastroesophageal reflux is the retrograde movement of gastric
contents from the stomach in to the esophagus
• When the esophagus is repeatedly exposed to refluxed material for
prolonged period of time, inflammation of the esophagus (reflux
esophagitis) occurs,and in some cases it can progress to erosion of
the squamous epithelium of the esophagus (erosive esophagitis).

3. PREVALENCE
• Occurs in both adults and children
• Mortality associated with GERD is rare (1 in 100000patients )
• True prevalence and incidence of GERD is difficult to assess because
(a)many patients do not seek medical treatment
(b) symptoms do not always correlate well with severity of the disease
(c) there is no standardizeddefinition or universal gold standard method for
diagnosing the disease
• Approximately 44% of the American population suffer from GERD
symptoms monthly and and more than 20% suffer with symptoms on a
weekly basis

4. PREVALENCE
• The prevalence of GERD varies depending on the geographic region
but appears highest in western countries.
• The prevalence increase in adults older than 40 years of age
• Although gender does not play a major role in the development of
GERD, it is and important factor in the development of Barrett’s
esophagus. BE is most prevalent in Caucasian adult males in western
countries.
• Systematic review found that the prevalence of symptomatic GERD to
be as high as 10%-20% in western world as compared to prevalence
of less than 5% in Asia

5. ETIOLOGY
The causes of GERD are associated with factors that increase the frequency
or duration of GER leading to increased contact of the acidic refluxate with
the esophageal mucosa. Such as :
• Distension of the stomach
• Delayed emptying of the stomach
• large sliding hiatal hernia
➢Any factor that relaxes the LES
➢Any factor that increases the abdominal pressure auch as obesity, tight
clothing, pregnancy
➢Older age or a debilitating condition that weakens the LES tone

6. CONTRIBUTING FACTORS
Factors leading to decreased LES pressure
• Chocolate
• Alcohol
• Fatty meals
• Coffee,tea
• Garlic
• Onions
• Smoking

7. Drugs that decrease the LES pressure :
• Theophylline
• Prostaglandins
• Estrogens/progestron ,oral contraceptives
• Nitrates / other Vasodilators
• Meperidine
• Dopamine
• Diazepam
• Calcium channel antagonists
• Beta adrenergic agonists
• Anti cholinergic agents (eg : TCA, antihistamines)
• Alpha adrenergic agonists

8. Factors irritating gastric mucosa :
• Fatty & spicy foods
• Citrus juices
• Tomato based products
• Coffee
• Medicines like NSAIDs, aspirin,KCl
Factors that stimulate acid secretions
• Soda
• alcohol
• smoking

9. Pathophysiologyof GERD

10. PATHOPHYSIOLOGY
(1) Lower esophageal sphincter pressure
(2) Anatomic factors
(3) Esophageal clearance
(4) Mucosal resistance
(5) Composition of refluxate
(6) Gastric emptying

11. LowerEsophageal SphincterPressure

12. • The sphincter is normally in a tonic statepreventing the reflux of gastric material
from the stomach but relaxes on swallowing to permit the free passage of food in
to the stomach
• Patients with more severe GERD have resting lower esophageal sphincter pressure
below 5mmHg. Transient decreases in the sphincter pressure are responsible for
approximately 65% of the reflex episodes in patients with GERD.
• LES pressure depends upon numerous factors including degree of sphincter
relaxation, efficacyof esophageal clearance, patient position, gastric volume and
intragastric pressure.
• Reflux may occur due to increase in intra abdominal pressure that occurs during
coughing, eating, pregnancy condition etc
• The LES may be atonic thus permitting free reflux
• Pregnancy, Achalasia( condition in which normal muscular activity of the
esophagus is disturbed) and scleroderma(persistant hardening and contraction of
the connective tissue) are conditions in which reflux is common

13. AnatomicFactors
The size of the HIATAL HERNIA is proportional to
the frequency of transient LES relaxations.
Patients with hypotensive lower esophageal
sphincter pressure and large Hiatal Hernias are
more likely to experience gastro esophageal reflux
following abrupt increases in intra abdominal
pressure as compared to patients with
hypotensive LES and no Hiatal Hernia.

14. Esophageal Clearance
• GERD patients with esophagitis have prolonged acid clearance time from the
esophagus. The symptoms and severity of esophageal reflux are partially
dependent on the duration of contact between the gastric contents and
esophageal mucosa. The contact time is in turn dependant on the rate at which
the esophagus clears the noxious material and frequency of reflux.
• The esophagus is cleared by primary primary peristalsisin response to
swallowing ,secondary peristalsisin response to esophageal distension and
gravitational effects.
• Swallowing contributes to esophageal clearance by increasing salivary flow.
Saliva contains bicarbonate that buffers the residual gastric material on the
surface of esophagus. The production of saliva decreases with increasing age
making it more difficult to maintain a neutral intraesophageal pH. therefore
esophageal damage due to reflux occurs more often in the elderly

15. Mucosal Resistance
• Within the esophageal mucosa and submucosa there are mucus
secreting glands. The mucus secreted by these glands may contribute
to the protection of the esophagus. Bicarbonate moving from blood
to the lumen can neutralize acidic refluxate in the esophagus.
• When the mucosa is repeatedly exposed to the refluxate in GERD or if
there is any defect in the normal mucosal
defences, hydrogen ions diffuse in to the
mucosa, leading to the cellular acidification
and necrosis that ultimately cause esophagitis

16. Gastric Emptying
• Delayed gastric emptying contributes to gastro esophageal reflux. An
increase in gastric volume may increase both the frequency of reflux
and amount of gastric fluid available to be refluxed.
• Gastric volume is related to the volume of material ingested, rate of
gastric secretion, rate of gastric emptying & amount of frequency of
duodenal reflux to stomach
• Factors that increase gastric volume and decrease gastric emptying are
associated with gastro esophageal reflux
• Fatty foods may increase post prandial gastro esophageal reflux by
increasing gastric volume, delaying gastric emptying rate & decreasing
the LES pressure

17. Compositionof Refluxate
• The composition and volume of refluxate are the most important
aggressive factors on determining the consequences of gastro
esophageal reflux.
• Acids have two primary effects when it refluxes in to the esophagus:
- if the pH of the refluxate is <2, esophagitis may develop secondary
to protein denaturation
- in addition pepsin is activated at this pH and may also cause
esophagitis
• Alkaline esophagitis refers to esophagitis induced by the reflux of
bilious and pancreatic fluid

18. • An increase in gastric bile concentrations may be caused by
duodenogastric reflux because of a generalized motility disorder or
slower clearance of refluxate
• Bile acids have both a direct irritant effect on the esophageal mucosa
and an indirect effect of increasing hydrogen ion permeability of
mucosa, symptoms are more often related to acid reflux than to bile
reflux

19. ClinicalPresentation
• Typical symptoms
• Atypical symptoms
• Complicated symptoms

20. Typical Symptoms
May be aggrevated by activities that worsen gastro esophageal reflux
such as recumbent position, bending over, or eating a meal high in fat.
• Heartburn
• Water brash (hypersalivation)
• Belching
• regurgitation

21. Atypical Symptoms
In some cases these extra esophageal symptoms may be the only
symptoms present, making it more difficult to recognize GERD as the
cause, especially when endoscopic studies are normal
• Nonallergic asthma
• Chronic cough
• Hoarseness
• Pharyngitis
• Chest pain
• Dental erosions

23. ComplicatedSymptoms
These symptoms may be indicative of complications of GERD such as
Barrett’s esophagus, esophageal strictures or esophageal cancer.
• Continual pain
• Dysphagia (difficulty in swallowing)
• Odynophagia (painful swallowing)
• Bleeding
• Unexplained weight loss
• Choking (acid causing cough, shortness of breath)

24. COMPLICATIONS
•ESOPHAGITIS
•BARRETT’S ESOPHAGUS
•ESOPHAGEAL STRICTURE & ULCERS
•ESOPHAGEAL ADENOCARCINOMA
•ASPIRATION
•ANEMIA
•HAEMORRHAGE

25. ESOPHAGITIS
• It is the inflammation that damage tissue of esophagus
• It can cause painful ,difficult swallowing and chest pain
• Reflux esophagitis – occurs because of the recurrent backing up of
stomach acid in to the esophagus and which results in the tissue
damage.
• Diagnosis- barium X ray & Endoscopy

26. LOS ANGELES (LA) CLASSIFICATION
SYSTEM-
Grade A Reflux Esophagitis
Grade A : one or more mucosal break, no longer than 5mm that does
not extent between the tops of two mucosal folds.

27. LA ClassificationSystem-
Grade B RefluxEsophagitis
Grade B : one or more mucosal breaks more than 5mm long that does
not extend between the tops of two mucosal folds.

28. LA ClassificationSystem-
Grade C RefluxEsophagitis
Grade C : one or more mucosal break that is continuos between the
tops of two or more mucosal folds, but which involves less than 75% of
the circumference

29. LA ClassificationSystem-
Grade D RefluxEsophagitis
Grade D : One or more mucosal break that involves at least 75% of the
esophageal circumference.

30. Barrett’s Esophagus
• Pre malignant glandular intestinalmetaplasia of the lower esophagus in
which the normal squamous lining is replaced by columnar epithelium.
• Occurs as an adaptive response to the Chronic GERD.
• Approximately 10-15%of patients with GERD will go on to develop
Barrett’s esophagus
• Identified endoscopically as salmon pink mucosa above the lower
esophageal sphincter.
• Major risk factor for esophageal adenocarcinoma with a life time cancer
risk of 10%, more closely related to the severity and duration of reflux
• The cancer incidence is estimated at 1 in 200 patients per year
• Prevalence is increased in men ( Caucasianmale) more than 50 yrs age

32. Barrett’s Esophagus to Esophageal
Adenocarcinoma : Degree of tissue change
• No Dysplasia – if barrett’s esophagus is present but no precancerous
changes are found in the cells
• Low grade dysplasia – if cells show small signs of precancerous
changes
• High grade dysplasia – if cells show many changes. High grade
dysplasia is thought to be the final step before cells change in to
esophageal cancer

34. Esophageal Srticture
• It is the narrowing of esophagus
• Develop as a consequence of long standing esophagitis
• Present with dysphagia which is worse for solid than liquid
• Diagnosis is made by endoscopy, barium X ray , esophageal
manometry with biopsies to exclude cancer
• Endoscopic balloon dilation is the treatment procedure
• Subsequently long term therapy with PPI at full dose should be started to reduce
the risk of recurrent esophagitis and stricture formation.

35. Esophageal Ulcer
• It is an open sore in the lining of the mucosa
• Characteristically produce severe and unrelenting
pain with the other common symptoms.
• Brisk haemorrhage may be caused by erosion of
an esophageal artery
• The ulcer usually is in columnar epithelium
• The presence of an ulcer can be suspected on a barium swallow and
confirmed endoscopically

36. DIAGNOSIS
• PATIENT HISTORY
• ENDOSCOPY
• BARIUM RADIOGRAPHY
• ESOPHAGEAL MANOMETRY
• AMBULATORY pH MONITORING
• OMEPRAZOLE TEST

37. ENDOSCOPY
• Endoscopy procedure involves inserting a long flexible tube in to the
esophagus and stomach. The camera attached to the endoscope
examines the esophagus, stomach and the duodenum
• It enables visualization and biopsy of the esophageal mucosa

38. Endoscopic Classification of ESOPHAGITIS
• Grade 0 – normal esophageal mucosa
• Grade 1 – erythema or diffusely red mucosaand
edema causing accentuated folds
• Grade 2 – isolated round or linear erosions
extending from the gastroesophageal junction
upwards, not involving the entire circumference
• Grade 3 – confluent erosions extending around the
entire circumference or superficial ulceration
without stenosis
• Grade 4 – complicatedcases ( barett’s esophagus,
stricture )

39. BariumRadiography
• The test involves drinking a barium solution and X-RAY imaging is
used to examine the upper digestive tract

40. Esophageal Manometry
• A multilumen tube is passed in to the stomach and the pressuresare measured
as the tube is pulled back across LES, esophagus and pharynx
• It is used to evaluate the peristaltic function and strength of the esophageal
muscles

41. AmbulatorypH Monitoring
• Continuos pH monitoring is performed by passing a small electrode
pH probe intranasally and placing it 5cm above the LES and monitors
esophageal acid exposure.

42. OmeprazoleTest
• The empiric use of standard dose or even double dose, omeprazole
has as a therapeutic trial for diagnosing the presence of GERD
• Sensitivity & specificity of omeprazole 60 mg daily for 7 days as the
initial diagnostic tool were similar to that obtained with ambulatory
pH monitoring.

43. TREATMENT

44. THERAPEUTIC GOALS :
• Eliminate the patients symptoms
• Decrease the frequency or recurrence and duration of gastroesophageal reflux
• Promote healing of the injured mucosa
• Prevent the development of complications
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
• Protecting the esophageal mucosa

45. Non Pharmacological Treatment
• Elevate the head of the bed (increases esophageal clearance).
• Avoid foods that may decrease LES pressure (fats, chocolate, alcohol, peppermint,spearmint)
• Avoid foods that have a direct irritant effect on the esophageal mucosa (spicy foods, orange
juice, tomato juice, coffee)
• Include protein rich meals in diet ( augments LES pressure )
• Eat small meals and avoid eating 2 hours prior to sleeping ( decreases the gastric volume).
• Weight reduction ( reduces symptoms)
• Smoking cessation (decreases spontaneous esophageal sphincter relaxation)
• Avoid alcohol( increases amplitude of LES, peristaltic waves & frequency of contraction )
• Avoid tight fitting clothing
• Discontinue, if possible, drugs that may promote reflux (CCB, Beta blockers, nitrates,
theophylline)
• Take drugs that have direct irritant effect on the esophageal mucosa with plenty of liquid if they
cannot be avoided ( tetracyclines, quinidine, iron salts, aspirin, NSAIDs)

46. SurgicalIntervention
The goal of antireflux surgery is to re-establishthe anti reflux barrier to
position the LES within the abdomen where it is under positive(intra
abdominal )pressure, and to close any associated hiatal effect.
It should be considered in patients
a) Who fail to respond to pharmacological treatment
b) Who opt for surgery despite successfultreatment because of lifestyle
considerations including age, time or expense of medication
c) Who have complications of GERD
Surgical procedures include Nissen,Belsey,Toupetand hill fundoplication

48. EndoluminalTherapies
ENTERYX

50. Endoscopic
stapling

52. PHARMACOLOGICAL
TREATMENT

53. ANTACIDS & ANTACID-ALGINIC ACID PRODUCTS
• Antacids increases LES pressure by neutralization of gastric acid
• An antacid product combined with alginic acid form a highly viscous
solution that floats on the surface of gastric contents
• This viscous solution serves as a protective barrier for the esophagus
against reflux of gastric contents
• It also reduces the frequency of reflux episodes
• Eg: GAVISCON
• ADR : Diarrhoea or constipation ,alterations in mineral metabolism, acid
base disturbances
• Typical doses – two tablets after meals and at bedtime
syrup-one tablespoon fourtimes daily

54. ACID SUPPRESSION WITH H2 RECEPTOR BLOCKERS
• Competitively block the histamine (H2) receptor of acid producing parietal calls
• Mainstay of treatment for the mild to moderate GERD.
• For symptomatic relief of mild GERD,low-dose, non prescription H2 receptor
antagonists may be beneficial
• For non erosive disease H2 receptorantagonists are given at standard doses twice
daily
• For non responding patients and for erosive disease higher doses or dosing four
times daily provide better acid control especially after mealtime acid surges.
cimetidine 800mg twice daily
famotidine 40 mg twice daily
nizatidine 150 mg four times daily
ranitidine 150 mg four times daily
• ADR: head ache , diarrhoea, fatigue, dizziness

55. ACID SUPPRESSION WITH PROTON PUMP
INHIBITORS
• Proton pump inhibitors block gastric acid secretion by inhibiting gastric
H+/K+ adenosine triphosphatase in gastric parietal cells
• This produces profound, long lasting anti secretory effect capable of
maintaining the gastric pH.
• DOSING:
• Omeprazole 20 mg
• Esomeprazole 20 mg
• Lansoprazole 30mg
• Rabeprazole 20 mg
• Pantoprazole 40 mg per day
• Timing : best is before 30 mins of food

56. PROKINETIC AGENTS
• Given to the patients who have failed high dose PPI therapy
• Have also been used as adjunctive therapy with an H2 receptor antagonist
• Enhances motility of smooth muscle from esophagus through the proximal small bowel
• Accelerate gastric emptying and transit of intestinal contents from duodenum to ileocecal
valve.
• Results of therapy:
- improved gastric emptying
- enhanced tone of the LES
- stimulated esophageal peristalsis (cisapride)
Dose :
Cisapride 5-20 mg
Metoclopramide 5-10mg
bethanechol 50 mg

57. Cisapride
• No longer available for routine use because of life threatening
arrhythmias when it is combined with certain medications and other
disease states.
• Available only through an investigational limited access program for
patients who have failed all other treatment options.

58. Metoclopromide
• Dopamine antagonist
• Increases LES pressure in a dose related manner and accelerates
gastric emptying in GERD patients.
• ADR: Diarrhoea,drowsiness,restlessness,depression,dystonia
• Side effects and the incidence of tachyphylaxiswith continued use
limits its usefulness
• Risk of adverse effects is more in patients with renal dysfunction

59. MUCOSAL PROTECTANTS
SUCRALFATE :
• It is a non absorbable aluminium salt of sucrose octasulfate, has very
limited value in the treatment of GERD
• Sucralfate has a similar healing rates as H2 receptor antagonists for
patients with mild esophagitis. Less effective than H2RAs in refractory
esophagitis
• Dose : 1g/10ml
• ADR: constipation, nausea,dry mouth , dizziness

60. MAINTENANCE THERAPY
• Patients who have symptomaticrelapse following discontinuation of
therapy or lowering of dose, including patients with complications such as
BE,strictures should be considered for long term maintenance therapy to
prevent complications or worsen esophageal functions.
• H2 receptor antagonists may be effectivemaintenance therapy for patients
with mild disease
• Proton pump inhibitors are the drug of choice for maintenance treatment
of moderate to severe esophagitis
• Lower doses of PPI or alternate day dosing may be effectivein patients
with less severe disease.
• Antireflux surgery and other endoluminal procedures may also be
considered a viable alternativeto long term drug therapy for maintenance
of healing in patients who are candidates.

61. SPECIAL POPULATION : PEDIATRIC PATIENTS
• Developmental immaturity of the LES is a cause for GERD in infants
• Uncomplicated gastro esophageal reflux usually resolves without incident
by 12-18 months
• Treatment :
-supportive therapy :
diet adjustments- smaller,more frequent thickened feedings
postural management
- ranitidine 2mg/kg twice daily is effective
- lansoprazole a dose of 15 mg once daily is recommended for children
weighing < 30 kg and a dose of 30 mg once daily is recommended for those
weighing > 30 kg .

62. SPECIAL POPULATION : PREGNANCY
• Common due to decreased LES pressure and increased intra
abdominal pressure
• Antacids other than sodium bicarbonate is generally considered safe
but high doses should be avoided

63. SPECIAL POPULATION : ELDERLY PATIENTS
Many elderly patients have decreased host defence mechanism such as
saliva production.
Often these patients do not seek medical attention because they feel
it’s a part of normal aging process
They may present with atypical symptoms such as chest pain, asthma,
hoarseness, coughing, wheezing, poor dentition
PPIs are medications of choice for acute episodes and prevention of
recurrence due to efficacy, safety and tolerability

64. EVALUATION OF THERAPEUTIC OUTCOME
• Successful outcomes are generally measured in terms of three points:
(a) Relieving symptoms
(b) Healing the injured mucosa
(c) Preventing complications

65. DIAGNOSTIC ADVANCES
MUCOSAL
IMPEDANCE SALIVARY
PEPSIN TEST
HIGH
RESOLUTION
MANOMETRY

66. NARROW BAND
IMAGING
BRAVO CAPSULE
TEST

67. THERAPEUTIC ADVANCES
• Immediate release omeprazole/
sodium bicarbonate
• 5HT4 Receptor Antagonist
• Baclofen
• Dexlansoprazole
• Potassium competitive acid blockers (P-CABs)

68. REFERENCES:
• Text book of Clinical Pharmacy and Therapeutics- Roger and Walker
• Pharmacotherapy Handbook- Barbara G wells
• www.webmd.com
• https://my.clevelandclinic.org
• www.niddk.nih.gov
• www.ncbi.nlm.nih.gov
• www.modahealth.com
• www.researchgate.net
• www.mdpi.com