‫بسم هللا الرحمن الرحيم‬

‫"و قل رب زدنى علما"‬

Gastro
Esophageal
Reflux
Disease
Presented by
Aya Elattar
 Difference between GER and GERD
• The passage of gastric contents into the esophagus
(gastroesophageal reflux) is a normal physiologic process.
Most episodes are brief and do not cause symptoms,
esophageal injury, or other complications.

• Gastroesophageal reflux becomes a disease when it

either causes macroscopic damage to the esophagus or
causes symptoms.
Difference between GER and GERD
 Pathophysiology
• Imbalance between aggressive and protective forces

Aggressive factors Protective factors

1- Acid 1- Lower esophageal sphincter

2- Pepsin (LES)
2- Esophageal clearance
3- Esophageal mucosal defense
4- Gastric emptying rate
5- Salivary buffering
 GERD Symptoms
Typical symptoms Extraesophageal or Alarm symptoms
atypical symptoms

1- Heartburn (it is the most 1- Noncardiac chest pain dysphagia, odynophagia,

common GERD symptom and is 2- laryngeal and pulmonary bleeding, vomiting, weight
described as substernal burning symptoms such as hoarseness, loss, choking, anemia.
sensation rising from the epigastrium throat clearing, chronic cough,
up toward the neck) and conditions such as laryngitis,
and pharyngitis.
2- Regurgitation (it is the 3- also GERD might exacerbate
effortless return of gastric contents asthma (asthma-like symptoms)
upward toward the mouth, often
accompanied by an acid or bitter
taste)

Refer for additional testing Immediate refer

 GERD Diagnosis
• There is no gold standard for the diagnosis of GERD.
• Thus, the diagnosis is based on a combination of:
1- symptom presentation
2- endoscopic evaluation of esophageal mucosa
3- reflux monitoring
4- response to therapeutic intervention

• Heartburn and regurgitation remain the most sensitive and specific

symptoms for GERD
• Atypical extraesophageal symptoms have poor sensitivity and specificity for
the diagnosis of GERD
Endoscopic evaluation of esophageal mucosa

For patients with GERD symptoms who also have alarm symptoms such as dysphagia,
weight loss, bleeding, vomiting, and/or anemia, endoscopy should be performed as soon
as feasible
Reflux monitoring
 GERD Complications
• Erosive esophagitis (EE)
• Esophageal stricture
• Barrett’s esophagus(replacement of squamous epithelial cells with
columnar epithelial cells within the lower esophagus, resulting in
increased risk of esophageal carcinoma)
• Esophageal cancer
GERD Risk factors
Risk factors (Drugs)
• Drugs reduce LES tone : • Drugs cause direct irritation:
✓ Calcium channel antagonists ✓NSAIDs
(verapamil, diltiazem, nifedipine,..)
✓Aspirin
✓ Nitrates (isosorbide dinitrate) ✓Corticosteroids
✓Iron
• Anticholinergic ✓Alendronare
[chlorphenamine1st gen antihistaminic
(brompheniramine, diphenhydramine, doxylamine,
Pheniramine, promethazine & triprolidine).
✓ and TCA : imipramine, nortriptyline,
amitriptyline]

✓ Oral contraceptives and estrogens (ethinyl

estradiol)
Risk factors (Food)
• food reduces LES tone :
✓Chocolate
✓Mint
✓High fat food
• Food irritates esophagus:
✓Tomato
✓Coffee
✓Citrus juice
Risk factors (Obesity)
Obesity increases the risk of GERD,
possibly because of a combination of:
1- eating a diet high in fat and other
foods that promote reflux.

2- increased intra-abdominal pressure

that promotes reflux because of
increased intra-abdominal fat.
Risk factors (Hiatal hernia)
 GERD management

Lifestyle Pharmacological surgery

modification therapy
Lifestyle modification
• Dietary modifications if symptoms are associated
with certain foods or drinks. Routine global
elimination of food triggers is not recommended.
• Avoid medications that can reduce LES pressure,
delay gastric emptying (opiates, tricyclic
antidepressants, calcium channel blockers,
progesterone), or cause direct irritation.
• Elevate the head of the bed 6 inches.
• Eat 3 hrs. before going to bed.
• Stop smoking.
• Reduce the size of the meal.
• Weight loss.
Pharmacological
therapy
• The backbone of pharmacologic
therapy for GERD are medications that
are directed at neutralization or
reduction of gastric acid.

• Agents in this class include antacids,

H2RA, and PPIs.
Antacids
• Neutralizing acid and raising intragastric pH.
• Calcium-, aluminum-, and magnesium-based
products are available OTC.
• Rapid onset of action but short duration,
necessitating frequent dosing. (Onset within 5
min & Duration 1-3 hours)
• Adverse reactions: Constipation (aluminum,
calcium), diarrhea (magnesium).
• Combination of AL, Mg salts is the best
• Taken just after meals and at bed time
31
Patient information
❑Patients with renal failure should avoid the use of all
antacids.
❑Antacids can interfere with the absorption of many
drugs. In general, antacids should be spaced at least 2
hours apart from the administration of interacting
drugs. Important clinical interactions with antacids
may occur with the following drugs:
• Tetracycline antibiotics
• Quinolone antibiotics (e.g., Ciprofloxacin,
Levofloxacin)
• Iron suppléments
• Digoxin
Alginic acid
• React with Na bicarbonate and saliva to form a viscous solution of
sodium alginate.
• Floats on the surface of gastric contents
• When reflux occurs, sodium alginate is refluxed, and irritation is
minimized

33
Alginic acid
➢Patient information
• Chewed followed by a glass of water
• Work best when patients are in the upright position
• Shouldn’t be taken at bedtime

34
Alginic acid
• Some Antacids products also contain the anti-refluxant alginic acid,
which forms a viscous layer on top of gastric contents to act as a
barrier to reflux.
Histamine-2 Receptor Antagonists (H2RAs)
• Reversibly inhibit histamine-2 receptors on the parietal cell.
• Available as prescription and/or OTC products.
H2 blockers
• Cimetidine, famotidine, ranitidine and Nizatidine
• Onset after 1-2 hrs
• Duration up to 10 hrs
• Taken 1 hr before eating
• Cimitidine and ranitidine inhibit CYP450
• S.E : headache, D,N, dizziness

37
(H2RAs)
• Recent U.S. Food and Drug Administration (FDA) safety alerts have
resulted in withdrawal from the market of ranitidine products
because of the presence of N-nitrosodimethylamine (NDMA), a
carcinogen.
• Prolonged use is associated with the development of tolerance and
reduced efficacy (tachyphylaxis).
• Adverse effects: Most are well tolerated. Central nervous system
(CNS) effects such as headache, dizziness, fatigue, and confusion.
 Proton pump inhibitors (PPIs)
• Most effective agents for short- and long-term management of
GERD and for management of erosive disease .
• Irreversibly inhibit the final step in gastric acid secretion.
• greater degree of acid suppression achieved and typically longer duration
of action than H2RAs.
• superior heartburn and regurgitation relief, as well as improved healing
compared with H2RAs.
• Several PPIs are available (e.g., omeprazole, lansoprazole, pantoprazole,
dexlansoprazole).
• Omeprazole, lansoprazole, and esomeprazole available OTC.
• OTC drugs should be used for no more than 14 days every 4 months unless
directed by a physician.
PPI
• Onset 2-3 hrs
• Duration 12-24 hrs
• May be 3 days

43
PPIs
• PPIs can bind only to proton pumps that are actively secreting acid
(meals stimulate proton pump activity).
• Traditional PPIs (omeprazole, lansoprazole, pantoprazole,
rabeprazole, and esomeprazole) should be given 30–60 minutes
before meals
• Newer PPIs (omeprazole-sodium bicarbonate and dexlansoprazole)
offer dosing flexibility in relation to meals
• Initiate PPIs once daily before a.m. meal
• Twice-daily PPIs if partial response to once-daily PPIs or nighttime
symptoms
• Adverse reactions: Overall, well tolerated; possible adverse effects
include headache, dizziness, nausea, diarrhea, and constipation.
PPIs (OTC)
Vonoprazan

• The FDA has approved vonoprazan 10 mg and 20 mg tablets to treat

adults with all grades of erosive esophagitis, or erosive GERD

• The approval of vonoprazan for erosive GERD was based on results

from the phase 3 PHALCON-EE study.

• Oral potassium-competitive acid blocker (PCAB), provides more

potent inhibition of gastric acid than PPIs and is seen as a potential
alternative.
 Vonoprazan
• Indicated for healing of all grades of erosive esophagitis and relief of associated
heartburn (20 mg PO qDay x 8 weeks)

• Indicated to maintain healing of all grades of erosive esophagitis and relief of

associated heartburn (10 mg PO qDay for up to 6 months)

• Dosage Modifications
• Renal impairment & Hepatic impairment
• Healing of erosive esophagitis
• eGFR ≥30 mL/min &Mild hepatic impairment (Child-Pugh A): : No dosage adjustment is
required
• eGFR <30 mL/min & Moderate or severe (Child-Pugh B or C): : Reduce dose to 10 mg PO qDay
• Maintenance of healed erosive esophagitis
• All severities: No dosage adjustment required
Mechanism of action
• Potassium-competitive acid blocker (PCAB)
• Suppresses basal and stimulated gastric acid secretion at secretory surface of gastric
parietal cell through inhibition of the H+, K+-ATPase enzyme system in a potassium
competitive manner
• Because this enzyme is regarded as the acid (proton) pump within the parietal cell,
vonoprazan has been characterized as a type of gastric proton-pump inhibitor, as it
blocks the final step of acid production
• Does not require activation by acid; may selectively concentrate in parietal cells in
both resting and stimulated states
• Binds to active proton pumps in non-covalent and reversible manner
• Although both classes of drugs inhibit the H+, K+-ATPase, the mechanism of action of
PCABs differs from that of proton-pump inhibitors (PPIs). PPIs form a covalent
disulphide bond with a cysteine residue on the H+, K+-ATPase, which leads to the
inactivation of the enzyme, while PCABs interfere with the binding of K+ to the H+, K+-
ATPase.
Efficacy of Vonoprazan vs. PPI
Prokinetics
• Metoclopramide has been shown to increase LES
pressure, enhance esophageal peristalsis, and augment
gastric emptying.
• Moderate to severe GERD

• However, data on its efficacy in GERD are scant, and

significant adverse events have been reported with long-
term and high-dose metoclopramide use.

• We recommend against treatment with a prokinetic

agent of any kind for GERD therapy unless there is
objective evidence of gastroparesis.
Sucralfate
• Sucralfate is a mucosal protective agent,
but few data document its efficacy in GERD.

• There is little to recommend for this agent

in GERD outside of pregnancy.
 Pharmacological therapy
Initial treatment depends on the severity, frequency, and duration of symptoms.

Step down Step up

➢ Starting with maximal therapy, such as ➢ Starting with lower-dose over-the-counter

therapeutic doses of PPIs, is always (OTC) products for patients with less
appropriate as a first-line strategy in severe symptoms without evidence of
patients with documented esophageal esophageal erosion.
erosion. ➢ Advantages: avoids overtreatment, has
➢ Advantages: rapid symptom relief, lower initial cost.
avoidance of over-investigation. ➢ Disadvantages: potential undertreatment
➢ Disadvantages: potential overtreatment, (partial symptom relief; may take longer
higher cost, increased potential for adverse for symptom control; may lead to over-
effects. investigation).
Step up treatment

• Antacids: Used as first-line therapy for intermittent (less than twice weekly)
symptoms or as breakthrough therapy for those on PPI/histamine-2 receptor
antagonist (H2RA) therapy; not appropriate for healing established esophageal
erosions.

• H2RAs: OTC H2RAs can be used for on-demand therapy for intermittent mild-to-
moderate GERD symptoms; preventive dosing before meals or exercise is also possible.
Higher prescription doses are often necessary for more severe symptoms or for
maintenance dosing.

• PPIs: The OTC products are considered safe and effective for intermittent short-term (2
weeks) use in patients with typical heartburn symptoms. Long-term use of OTC
products should be discussed with prescriber to prevent loss of follow-up or to assess
for potential over or undertreatment.
Step down treatment

• For patients with classic GERD symptoms of heartburn and regurgitation who have no
alarm symptoms, we recommend an 8-week trial of empiric PPIs once daily before a
meal
• We recommend attempting to discontinue the PPIs in patients whose classic GERD
symptoms respond to an 8-week empiric trial of PPIs
• For patients who have both extraesophageal and typical GERD symptoms, we suggest
considering a trial of twice-daily PPI therapy for 8–12 weeks before additional testing
• For patients with GERD who do not have EE or Barrett’s esophagus, and whose
symptoms have resolved with PPI therapy, an attempt should be made to discontinue
PPIs
Step down treatment

• We recommend treatment with PPIs over treatment with H2RA for healing EE.
• We recommend treatment with PPIs over H2RA for maintenance of healing for
EE.
• Maintenance PPI therapy should be administered for patients with GERD
complications including severe EE (LA gradeC or D) and Barrett’s esophagus
• For patients with GERD who require maintenance therapy with PPIs, the PPIs
should be administered in the lowest dose that effectively controls GERD
symptoms and maintains healing of reflux esophagitis.
Step down treatment

• For patients without EE or Barrett’s esophagus who continue to have symptoms

when PPI therapy is discontinued, consideration can be given to on-demand
therapy in which PPIs are taken only when symptoms occur and discontinued
when they are relieved.
• Step-down therapy to H2RAs is another acceptable option for management,
particularly in patients with NERD
The safety of long-term PPI usage for GERD
• PPIs are the most effective medical treatment for GERD.
• Some medical studies have identified an association between the long-
term use of PPIs and the development of numerous adverse conditions
including intestinal infections, pneumonia, stomach cancer, osteoporosis-
related bone fractures, chronic kidney disease, deficiencies of certain
vitamins and minerals, and heart attacks.
• Those studies have flaws, not considered definitive.
• High-quality studies have found that PPIs do not significantly increase the
risk of any of these conditions except intestinal infections.
• Nevertheless, we cannot exclude the possibility that PPIs might confer a
small increase in the risk of developing these adverse conditions.
• For the treatment of GERD, gastroenterologists generally agree that the
well-established benefits of PPIs far outweigh their theoretical risks.
Surgery
Diagnosis of GERD
in pregnancy
• Approximately two-thirds of pregnant
women experience heartburn, which
can begin in any trimester.
• Pregnancy and the amount of weight
gain during pregnancy are risk factors for
frequent GERD symptoms 1 year after
delivery .
• Heartburn is the only GERD symptom
that has been studied in pregnancy, and
the diagnosis of GERD is almost always
symptom-based.
 Treatment of GERD in pregnancy

treatment of GERD during pregnancy should start with

lifestyle modifications.

When lifestyle modifications fail, antacids (aluminum-, calcium-, or

magnesium-containing), alginates, and sucralfate are the first-line
Refer

therapeutic agents.

All histamine H2- blockers are FDA category B, and

all PPIs are FDA category B except omeprazole,
which is FDA category C.
Pediatric patients
• GER occurs commonly in infants and children.
• Signs and symptoms in pediatric patients include vomiting, chest
pain, irritability, feeding refusal, belching, and apnea. Serious
complications (e.g., failure to thrive, esophageal strictures) can occur
in infants and children.
• Antacids, with or without alginic acid, have been widely used in
infants and children, but their safety has not been established.
• H2RAs have been used safely in children under the supervision of
health-care providers. However, the nonprescription H2RAs are not
approved for use in children younger than 12 years of age unless
directed by the physician
Elderly patients
• Antacids and nonprescription H2RAs may be safely used in elderly
patients without any dosage adjustments.
• Dosage reduction of prescription H2 RAs may be necessary in elderly
patients with reduced renal function.
• Elderly patients are more likely to be taking drugs that interact with
antacids, H2RAs, omeprazole, and/or cisapride.
• Elderly patients are more likely to have symptoms or conditions that
require referral to a physician before beginning nonprescription
therapy
Case study
• A 42 years old man in moderate distress passed by a
community pharmacist complaining of heartburn or burning
sensation located in the lower chest. These discomfortable
sensations usually occur soon after meals, when lying down,
at bedtime and after fatty or ketchup containing meal. He also
suffers from sensation of bitter taste in mouth after meals. He
also noted that he defecates three times a week. Up on
discussion, the man stated that he is a smoker, fond of eating
chocolate, drinking coffee. His medical history includes
diltiazem one year ago to control his hypertension. Levodopa
for his parkinsonian disease
Questions
1- The most assumptive diagnosis is:
A. GERD
B. Hyperacidity
C. Peptic ulcer
D. All of the above
E. None of the above
Questions
2- What are the symptoms of this disease ?
• Heartburn
• Discomfortable sensations soon after meals and when
lying down at bedtime and after fatty or ketchup
containing meal
• Sensation of bitter taste in mouth after meals
Questions
3. The cause of this patient condition is:
Lower esophageal muscle sphincter pressure
Questions
4-What are the causes of this disease (generally)?

• Imbalance between aggressive & protective factors

Questions
5- Drugs and food that reduce LES tone include:
• Drugs reduce LES tone :
1) Calcium channel antagonists
2) Nitrates
3) Anticholinergic
4) Oral contraceptives and estrogen
• Food reduce LES tone :
1) Chocolate
2) Mint
3) Fatty food
Questions
6- What are the non pharmacological treatments for
this disease?
• Elevate the head of the bed 6 inches
• Eat 3 hrs before going to bed
• Avoid foods reduce LES tone
(Chocolate, Mint, Fatty foods )
• Avoid foods irritate the esophagus
(Ketchup, Coffee, Citrus juice )
Questions
6- What are the non pharmacological treatments for this
disease?
• Reduce the size of the meal
• Avoid lying down after meals
• Stop smoking
• Limit caffeine containing beverages
• Limit alcohol intake
• Lose weight
• Avoid wearing tight clothes
Questions
7- Information and advises required for this
patient concern all the following Except:
A. Elevate the head of the bed about 6 inches with Blocks
B. Avoid Chocolate, High-fat foods Tomato-based products, Coffee,
and stop smoking
C. Reduce meal size and take evening meal 3 hr. before bedtime
D. Continue his antihypertensive medication
E. Increase dietary fiber and vegetables and make exercise
Questions
8- Select the most suitable antacid for relieving the
man heart burn
A. Sodium bicarbonate antacid
B. Calcium carbonate antacid
C. Aluminum containing antacid
D. Aluminum and magnesium containing antacid
E. None of the above
Questions
• 9- Contraindication of Sodium bicarbonate antacid
and why ?
• Edema
• Congestive heart failure
• Renal failure
• Cirrhosis
• Pregnancy
Questions
10- If the patient require proton pump inhibitors the
only OTC drug which is available is:
A. Pantoprazole
B. Dexlansoprazole
C. Omeprazole
D. Famotidine
E. Ranitidine
Questions
11- As this patient is poly-pharmacy, the less
interacting H2 blocker given safely to this patient
for managing his heart burn is:
A. Cimitidine
B. Omeprazole
C. Famotidine
D. Both a and c
E. Both b and c
Questions
• 12-what are side effects of selected one ?
• Nausea
• Headache
• Fatigue
• Dizziness
Questions
• 13- What is the mechanism of alginic acid and what
is the patient information you should know about it?
• forms a viscous layer on top of gastric contents to act as
a barrier to reflux
Questions
• 13- What is the mechanism of alginic acid and what
is the patient information you should know about it?
Patient information:
• Chewed followed by glass of water
• Work best when patients are in upright position
• Shouldn’t be taken at bedtime