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Pharmaco-therapeutics
2
GastroEsophageal Reflux
Disease (GERD)
Mohammad Ruhal Ain
R Ph, PGDPRA, M Pharm (Clin. Pharm)
Department of Clinical Pharmacy
E-mal: [email protected]
Case Study
• A .W 75-year-old man with a 3-year history of
severe GERD symptoms and Parkinson disease has
been taking lansoprazole 30 mg 2 times/day for 5
months.
• He has initiated proper nonpharmacologic
measures, including elevating the head of his bed,
reducing fat intake and portion size, avoiding tightfitting clothes, and losing weight.
•Because he continues to have daily heartburn
symptoms, he is referred for endoscopy, which
reveals normal-appearing mucosa and no structural
abnormalities.
Define GERD !
A condition which develops when reflux of
stomach contents causes troublesome
symptoms and/or complications
What are the symptoms of GERD ?
Symptoms of GERD
Typical symptoms
Heartburn (pyrosis)
Regurgitation Acidic taste
in the mouth
Extraesophageal symptoms
(formerly referred to as atypical)
Chronic cough, asthma-like Symptoms
recurrent sore throat, laryngitis/hoarseness,
dental enamel loss Non cardiac chest pain;
sinusitis/pneumonia/bronchitis/otitis media
are less common atypical symptoms.
Alarm symptoms
troublesome dysphagia, odynophagia, bleeding,
weight loss, choking, chest pain, and epigastric
mass
Odynophagia:
a dysphagia in which
swallowing causes pain.
Questions: Fill in the blank
• Pyrosis is ……………….
• Regurgitation and Acidic taste in the mouth are
………. Symptoms of GERD ( typical /atypical
/alarm )
•GERD stands for ………………………………….
•Recurrent sore throat, laryngitis/hoarseness, dental
enamel loss are ……………. Symptoms of GERD (
typical /atypical /alarm )
•Troublesome dysphagia odynophagia, bleeding are
………….. Symptoms of GERD ( typical /atypical
/alarm )
Questions: Fill in the blank
• Pyrosis is Heartburn
• Regurgitation and Acidic taste in the mouth are
Typical Symptoms of GERD ( typical /atypical
/alarm )
•GERD stands for Gastro-Esophageal Reflux Disease
•Recurrent sore throat, laryngitis/hoarseness, dental
enamel loss are atypical Symptoms of GERD (
typical /atypical /alarm )
•Troublesome dysphagia odynophagia, bleeding are
alarm Symptoms of GERD ( typical /atypical
/alarm )
What can aggravate M.W condition ?
Aggravating factors in GERD
I. Recumbency (gravity)
II. Increased intra-abdominal pressure
III. Reduced gastric motility
IV. Decreased lower esophageal sphincter
(LES) tone
V. Direct mucosal irritation
Question: Mention 3 aggravating factors in GERD?
True or false Questions
•(gravity) is considered to be an aggravating factor for GERD
?
[T]
[F]
• Increased lower esophageal sphincter (LES) tone is an
aggravating factor for GERD ?
[T]
[F]
•Increased intra-abdominal pressure is a complication for
GERD ?
[T]
[F]
Question: Mention 3 aggravating factors in GERD?
True or false Questions
•(gravity) is considered to be an aggravating factor for GERD
?
[T]
[F]
• Increased lower esophageal sphincter (LES) tone is an
aggravating factor for GERD ?
[T]
[F]
•Increased intra-abdominal pressure is a complication for
GERD ?
[T]
[F]
Long-term complications of GERD are ?
I. Esophageal erosion
II. strictures/obstruction
III. Barrett esophagus,
IV. and reduction in patient’s quality of life
lining of the esophagus is damaged by stomach
acid
Case Study
• A .W 75-year-old man with a 3-year history of
severe GERD symptoms and Parkinson disease has
been taking lansoprazole 30 mg 2 times/day for 5
months.
• He has initiated proper nonpharmacologic
measures, including elevating the head of his bed,
reducing fat intake and portion size, avoiding tightfitting clothes, and losing weight.
•Because he continues to have daily heartburn
symptoms, he is referred for endoscopy????????,
which reveals normal-appearing mucosa and no
structural abnormalities.
Diagnosis
I.Based on Symptoms ? ….in uncomplicated cases
- it is reasonable to assume a diagnosis of GERD in patient who
respond to initial acid-suppressive therapy, particularly proton
pump inhibitors (PPIs).
-Symptoms do not predict the degree of esophagitis or
complications secondary to GERD, if present.
-Patients presenting with extraesophageal symptoms should be
assessed on a case-by-case basis to consider the need for referral
or alternative/invasive testing.
- Cardiac etiologies (ischemic) should be considered and
explored before arriving at a diagnosis of reflux chest pain
syndrome.
-When to use endoscopy ?
Diagnosis
II. Endoscopy ……….
- Choice to identify Barrett esophagus (with
biopsy) or complications of GERD.
- 97% specific for the diagnosis of GERD
-Most patients with typical/atypical symptoms
will have normal-appearing esophageal mucosa
on endoscopy
I. Age > 45 years,
II. Patient with alarm symptoms (particularly
troublesome dysphagia
III. Refractory to initial treatment, as well as in
those with a preoperative assessment or possibly
when extraesophageal symptoms are present
Diagnosis
III. Manometry ……….
Used to evaluate peristaltic function of the
esophagus in patients with normal endoscopic
findings
Diagnosis
IV. pH testing ……….
The main outcome measure of esophageal pH monitoring is the
percentage of time the pH value is less than 4 in a 24-hour period.
Ambulatory pH testing is useful in the following clinical
situations:
i. Patients with no mucosal changes on endoscopy and
normal manometry who have continued symptoms
(both typical and atypical)
ii. Patients who are refractory to therapeutic doses of
appropriate pharmacologic agents
iii. Monitoring of reflux control in patients with continued
symptoms on drug therapy
- Sensitivity/specificity of 96% reported
- The PPIs should be withheld for 7 days before pH
testing, if possible, for the most accurate results.
True or false Questions
- It is reasonable to assume a diagnosis of GERD in patient
who respond to initial acid-suppressive therapy, particularly
proton pump inhibitors (PPI) ?
[T]
[F]
• Symptoms predict the degree of esophagitis or complications
secondary to GERD, if present. ?
[T]
[F]
•Most patients with typical/atypical symptoms of GERD will
have abnormal-appearing esophageal mucosa on endoscopy
[T]
[F]
True or false Questions
- It is reasonable to assume a diagnosis of GERD in patient
who respond to initial acid-suppressive therapy, particularly
proton pump inhibitors (PPI) ?
[T]
[F]
• Symptoms predict the degree of esophagitis or complications
secondary to GERD, if present. ?
[T]
[F]
•Most patients with typical/atypical symptoms of GERD will
have abnormal-appearing esophageal mucosa on endoscopy
[T]
[F]
Complete the following
•Endoscopy is the choice to identify ………………………… GERD
•most patients with typical/atypical symptoms of GERD will
have …………………………..on endoscopy
•Endoscopy is ……….. (specific /not specific ) for diagnosis
GERD
Complete the following
•Endoscopy is the choice to identify Barrett esophagus (with
biopsy) or complications of GERD
•Most patients with typical/atypical symptoms of GERD will
have normal-appearing esophageal mucosa on endoscopy
•Endoscopy is specific (specific /not specific ) for diagnosis
GERD
Case Study
• A .W 75-year-old man with a 3-year history of
severe GERD symptoms and Parkinson disease has
been taking lansoprazole 30 mg 2 times/day for 5
months.
• He has initiated proper nonpharmacologic
measures??????????, including elevating the head of
his bed, reducing fat intake and portion size, avoiding
tight-fitting clothes, and losing weight.
•Because he continues to have daily heartburn
symptoms, he is referred for endoscopy, which
reveals normal-appearing mucosa and no structural
abnormalities.
Treatment
•Treatment options for GERD
Nonpharmacologic
interventions/lifestyle modifications
Pharmacologic therapies
Nonpharmacologic
interventions/lifestyle modifications
A. Dietary modifications in patients whose symptoms are
associated with certain foods or drinks
i. Avoid aggravating foods/beverages; some may reduce
LES pressure (alcohol, caffeine, chocolate, citrus
juices, garlic, onions, peppermint/spearmint) or cause
direct irritation (spicy foods, tomato juice, coffee).
ii. Reduce fat intake (high-fat meals slow gastric
emptying) and portion size.
iii. Avoid eating 2–3 hours before bedtime.
iv. Remain upright after meal
Nonpharmacologic
interventions/lifestyle modifications
B. Weight loss for overweight or obese patients
C. Reduce/discontinue nicotine use in patients who use
tobacco products (affects LES).
D. Elevate the head of the bed (6–8 in.) if reflux is associated
with recumbency E. Avoid tight-fitting clothing (decreases
intra-abdominal pressure).
F. Avoid medications that may reduce LES pressure, delay
gastric emptying, or cause direct irritation:
α-Adrenergic antagonists, anticholinergics,
benzodiazepines, calcium channel blockers,
estrogen, nitrates, opiates, tricyclic antidepressants,
theophylline, NSAIDs, and aspirin
Answer the given questions:
•Generally , Nonpharmacologic treatment such as dietary
modifications of GERD options include …………………
•………… fat intake as dietary modification for GERD patient
( reduce /increase)
•………… eating 2–3 hours before bedtime ( avoid/ encourage)
as dietary modification for GERD patient
•Remain………….after meal as dietery modification for
GERD patient (upright /lay down )
• Reduce/discontinue nicotine use in patients who use
tobacco products (affects LES). ( T/F)
•In GERD patient Elevate the head of the bed (6–8 in.) if
reflux is associated with recumbency (T/F)
Pharmacologic therapies
Initial treatment will depend on severity, frequency, and duration of symptoms.
Strategies
“Step-down” treatment
“Step-up” 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
Starting with lower-dose OTC products.
Advantages: Rapid symptom relief,
avoidance of overinvestigation.
Advantages: Avoids overtreatment, has
lower initial drug cost.
Disadvantages: Potential overtreatment,
higher drug cost, increased potential of
adverse effects
Disadvantages: Potential undertreatment
(partial symptom relief), may take longer
for symptom control, may lead to
overinvestigation
Contain the anti-refluxant alginic acid,
which forms a viscous layer on top of
gastric contents to act as a barrier to
reflux
Aluminum hydroxide, magnesium hydroxide
and simethicone.
2. Symptomatic relief of GERD
3. Healing of erosive esophagitis or treatment of patients presenting with moderate to
severe symptoms or complications
True or false Questions
-PPIs are more effective than histamine2-receptor antagonists
(H2RA) ?
[T]
[F]
• All PPIs are similar in efficacy when used for patients with
esophageal GERD symptoms.
[T]
[F]
•Maintenance therapy is appropriate for patients with
esophagitis in whom PPIs have been effective Titration to the
lowest effective dose is recommended.
[T]
[F]
Drugs
Antacids
•Calcium-, aluminum-, and magnesium-based products are available
OTC in a wide variety of formulations (capsules, tablets, chewable
tablets, and suspensions).
•Side effects
Constipation (aluminum),
(magnesium), diarrhea
Accumulation of aluminum/magnesium in renal disease with
repeated dosing
Drug interactions: Chelation (fluoroquinolones, tetracyclines),
reduced absorption because of increases in pH (ketoconazole,
itraconazole, iron, atazanavir, delavirdine, indinavir, nelfinavir) or
increases in absorption leading to potential toxicity (raltegravir,
saquinavir)
Drugs
H2RAs ( (cimetidine, ranitidine, famotidine, nizatidine))
Side effects:
–Headache
–Somnolence
–Fatigue
–Dizziness
–Either constipation or diarrhea
•Cimetidine may inhibit metabolism of some drugs (e.g.,
theophylline, warfarin, phenytoin).
•They are equally effective; selection of agent based on
differences in pharmacokinetics, safety profile, and cost
•Elderly patients and those with reduced renal function are
more at risk.
•Prolonged cimetidine use is associated with rare development
of gynecomastia.
Drugs
•PPIs (dexlansoprazole, esomeprazole, lansoprazole,
omeprazole, pantoprazole,
–Side effects:
•Headache
•Dizziness
•Somnolence
•Diarrhea
•Constipation
•Nausea
•Vitamin B12 deficiency
–May facilitate Clostridium difficile infection during acid
suppression.
–Lansoprazole, esomeprazole, and pantoprazole available
in IV formulations, but are not more effective than oral
preparations and are more expensive.
•New FDA labeling for PPIs as of May 2010 stating
that PPIs may increase the risk of hip and spine
fracture
•Patients should take oral PPIs in morning 15–30
minutes before breakfast; dexlansoprazole can be taken
without regard to meals.
•If dosed twice daily, second dose should be taken 10–
12 hours after morning dose and prior to meal or snack
not bed time
Case Study
• A .W 75-year-old man with a 3-year history of
severe GERD symptoms and Parkinson disease has
been taking lansoprazole 30 mg 2 times/day for 5
months.
• He has initiated proper nonpharmacologic
measures, including elevating the head of his bed,
reducing fat intake and portion size, avoiding tightfitting clothes, and losing weight.
•Because he continues to have daily heartburn
symptoms, he is referred for endoscopy, which
reveals normal-appearing mucosa and no structural
abnormalities.
Q- Which one of the following is the best course of
action for this patient?
A. Add metoclopramide 10 mg 4 times/day and reassess
in 3 months.
B. Educate about the proper use of lansoprazole and
refer for manometry.
C. Add metoclopramide 10 mg 4 times/day and refer for
surgical intervention.
D. Add famotidine 20 mg/day at bedtime and reassess
in 4 months.