12/20/2016

Gastroesophageal Reflux Disease

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Pharmacotherapy of
Gastroesophageal Reflux
Disease (GERD)
By
Jastria Pusmarani, M. Sc., Apt
Jastria Pusmarani, M. Sc., Apt

20/12/2016

GERDkerusakan mukosa karena adanya aliran balik (reflux)

yang abnormal di esofagus perut
Esofagus yang abnormal lamanya material yang terekspos
di dalamnya, adanya inflamasi pada esofagus (reflux
esophagitis)
Faktor tersebut menyebabkan erosi pada epitel skuamosa
esofagus (erosive esophagitis)
Symptomp: Heartburn into the oesophagus,
causing heartburn, which occurs in about 75% of cases.
The oesophageal mucosa has little or no protection against the
acidity and proteolytic activity of the gastric juice.
Jastria Pusmarani, M. Sc., Apt

20/12/2016

Jastria Pusmarani, M. Sc., Apt

20/12/2016

Pathology of GERD
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Problems with other normal mucosal defense mechanisms, such as anatomic

factors esophageal clearance, mucosal resistance, gastric emptying,
epidermal growth factor, and salivary buffering, may also contribute to
the development of GERD.
In some cases, reflux is associated with defective lower esophageal
sphincter (LES) pressure or function.
Patients may have decreased LES pressure from spontaneous transient
LES relaxations, transient increases in intraabdominal pressure
Some foods and medications decrease LES pressure
Aggressive factors that may promote esophageal damage upon reflux
into the esophagus include gastric acid, pepsin, bile acids, and pancreatic
enzymes.
Jastria Pusmarani, M. Sc., Apt

20/12/2016

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Esophageal clearance
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In many patients with GERD, the problem is not that

they produce too much acid, but that the acid
produced spends too much time in contact with the
esophageal mucosa.
The esophagus is cleared by primary peristalsis in
response to swallowing, or by secondary peristalsis
in response to esophageal distension and
gravitational effects.
Swallowing contributes to esophageal clearance by
increasing salivary flow.
Jastria Pusmarani, M. Sc., Apt

Saliva contains bicarbonate that buffers the

residual gastric material on the surface of the
esophagus.
The production of saliva decreases with
increasing age, making it more difficult to
maintain a neutral intraesophageal pH.
Swallowing is also decreased during sleep,
making nocturnal GERD a problem in many
patients

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Jastria Pusmarani, M. Sc., Apt

20/12/2016

GASTRIC EMPTYING
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Delayed gastric emptying can contribute to

gastroesophageal reflux.
An increase in gastric volume may increase both the
frequency of reflux and the 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, and amount and frequency of duodenal
reflux into the stomach.
Jastria Pusmarani, M. Sc., Apt

20/12/2016

Factors that increase gastric volume and/or

decrease gastric emptying, such as smoking
and highfat meals, are often associated with
gastroesophageal reflux.
Fatty foods may increase postprandial
gastroesophageal reflux by increasing
gastric volume, delaying the gastric
emptying rate,

Jastria Pusmarani, M. Sc., Apt

20/12/2016

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20/12/2016

Jastria Pusmarani, M. Sc., Apt

MUCOSAL RESISTANCE
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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 the 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 a defect in the normal
mucosal defenses, hydrogen ions diffuse into the mucosa,
leading to the cellular acidification and necrosis that
ultimately cause esophagitis.

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In theory, mucosal resistance may be related not

only to esophageal mucus, but also to:
tight epithelial junctions,
epithelial cell turnover,
nitrogen balance,
mucosal blood flow,
tissue prostaglandins, and
the acidbase status of the tissue.
Saliva is also rich in epidermal growth factor,
Jastria Pusmarani, M. Sc., Apt 20/12/2016
stimulating cell renewal.

COMPOSITION OF REFLUXATE
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The composition, pH, and volume of the refluxate are

important aggressive factors in determining the
consequences of gastroesophageal reflux.
First, if the pH of the refluxate is less than 2,
esophagitis may develop secondary to protein
denaturation.
In addition, pepsinogen is activated to pepsin at this pH
and may also cause esophagitis.
Duodenogastric reflux esophagitis, or alkaline
esophagitis, refers to esophagitis induced by the reflux
Jastria Pusmarani, M. Sc., Apt 20/12/2016
of bilious and pancreatic fluid.

An increase in gastric bile concentrations may be

caused by duodenogastric reflux as a result of a
generalized motility disorder, slower clearance of the
refluxate, or after surgery.
Although bile acids have both a direct irritant effect on
the esophageal mucosa and an indirect effect of
increasing hydrogen ion permeability of the mucosa,
symptoms are more often related to acid reflux than to
bile reflux.
Specifically, the percentage of time that the esophageal
pH is below 4 is greater for patients with severe disease
Jastria Pusmarani, M. Sc., Apt 20/12/2016
as compared to those with mild disease.

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TREATMENT
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Jastria Pusmarani, M. Sc., Apt

20/12/2016

Jastria Pusmarani, M. Sc., Apt

GENERAL APPROACH
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Therapy is directed toward decreasing

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

Jastria Pusmarani, M. Sc., Apt

Goals of Treatment:
The goals are to reduce or eliminate symptoms,
Decrease frequency and duration of
gastroesophageal reflux,
Promote healing of injured mucosa,
And prevent development of complications

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Treatment is determined by disease

severity and includes the following:

Lifestyle changes and patient-directed therapy

with antacids and/or nonprescription acid
suppression therapy (histamine 2receptor
antagonists [H2RAs] and/or proton pump
inhibitors [PPIs])
Pharmacologic treatment with prescriptionstrength acid suppression therapy
Antireflux surgery
Jastria Pusmarani, M. Sc., Apt

20/12/2016

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NONPHARMACOLOGIC THERAPY
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Potential lifestyle changes depending on the patient

situation:
Weight

reduction for overweight or obese patients.

foods that decrease LES pressure.
Include protein-rich meals to augment LES pressure.
Avoid foods with irritant effects on the esophageal mucosa.
eating immediately prior to
Eat small meals and avoid
sleeping (within 3 hours if possible).
Stop smoking.
Avoid alcohol.
Avoid tight-fitting clothes.
Avoid

Jastria Pusmarani, M. Sc., Apt

20/12/2016

Jastria Pusmarani, M. Sc., Apt

Antacids and Antacid-Alginic Acid

Products

PHARMACOLOGIC THERAPY
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Terapi antasida menekan asam lambung (mild

GERD)
antacid with alginic acid Gaviscon
Tidak potent untuk menetralisir asam lambung,
tidak dapat meningkatkan tekanan LES tetapi
membentuk cairan kental yang melindungi
permukaan lambung.
Sebagai barrier protektif esofagus terhadap
reflux di lambung dan menurunkan frekuensi
episode reflux.

NEXT..
Jastria Pusmarani, M. Sc., Apt

20/12/2016

Jastria Pusmarani, M. Sc., Apt

20/12/2016

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Proton Pump Inhibitors (PPI)

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Memblok asam lambung melalui penghambatan

hidrogen potasium adenosin trifosfat di dalam sel
parietal lambung dan sebagai agen antisekretori longlasting.
PPI diberikan pada pasien dengan moderate to severe
GERD
Pasien diberikan PPI setiap 15-30 menit sebelum makan,
karena PPI menghambat sekresi asam pada pompa
proton.
Jastria Pusmarani, M. Sc., Apt

Umumnya dosis diberikan 1x sehari, tetapi jika pasien

tidak responsif , maka dapat diberika 2x sehari.
Jika dosis diberikan 2x sehari, maka dosis kedua dapat
diberikan 10-12 jam setelah pemberian dosis yang
pertama.
exlansoprazole,
esomeprazole,
lansoprazole,
omeprazole,
pantoprazole,
And rabeprazole

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Jastria Pusmarani, M. Sc., Apt

Promotility Agents

Histamine 2Receptor Antagonists (H2RAS)

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cimetidine,
ranitidine,
famotidine,
Nizatidine
Terbagi menjadi dua dosis dan efektif untuk terapi
pasien mild to moderate GERD
Efek samping CimetidinGinekomastia (sebaiknya
tidak digunakan pada pasien laki-laki)
Jastria Pusmarani, M. Sc., Apt

20/12/2016

sebagai

terapi tambahan untuk menekan asam

lambung yang mempangaruhi motilitas pasien
(menurunkan klirens esofagus, menghambat
pengosongan lambung)
Metoclopramide
agen antagonis dopamin
meningkatkan tekanan LES, mempercepat
pengosongan lambung.
Tidak dapat memperbaiki klirens lambung.
Jastria Pusmarani, M. Sc., Apt

20/12/2016

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Mucosal Protectants
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Sucralfate
Garam aluminium non absorbable dari
sukrosa oktasulfat.
Efektivitas terhadap GERD, tetapi ampuh
digunakan untuk manajemen radiasi pada
esofagus dan empedu atau Reflux yang
non acid pad GERD
Jastria Pusmarani, M. Sc., Apt

20/12/2016