Chapter 3

Heartburn and Dyspepsia

Lebanese International University
School of Pharmacy
Non-Prescription Drugs
Fall 2013 - 2014

Katia Iskandar, PharmD, MHM (Course coordinator)

Samar Younes , PharmD
Fouad Sakr, PharmD
Introduction

 Heartburn is a Burning sensation that usually arises from the

substernal area (lower chest) and moves up toward the neck or throat.

 Postprandial heartburn usually occurs within 2 hours after eating: A

large meal
◦ Trigger foods (e.g., spicy, citrus, or fatty)
◦ Beverages (e.g., alcohol)
◦ And when bending over or lying down

 Nocturnal heartburn awakens individuals and interferes with restful

sleep.
Introduction

Simple Heartburn
 Mild, infrequent, episodic, and associated with diet or lifestyle

Frequent Heartburn
 Occurs 2 or more days a week

Frequent and Persistent

 Lasting 3 or more months

 Typical symptom of GERD

Introduction

Dyspepsia (bad digestion)

 Consistent or recurrent discomfort located primarily in the

upper abdomen (epigastrium)

 Characterized by one or more symptoms of epigastric:

◦ Pain
◦ Burning
◦ Belching
◦ Postprandial fullness
◦ Early satiety
Introduction

 Heartburn may occur alone or be associated with acid-related disorders

such as dyspepsia, GERD, and PUD.

 In clinical practice, it is not always possible to determine the cause of

heartburn or dyspepsia on the basis of symptom assessment alone
because of the lack of specific symptoms.

 In addition, there is considerable overlap of symptoms among these

disorders.

 However, empiric treatment with nonprescription medications is

appropriate and reasonable for most patients who have symptoms
suggestive of heartburn and/or dyspepsia.
Pathophysiology

 Imbalance between aggressive and protective factors affecting

the esophageal mucosa

Protective Factors Aggressive Factors

Lower esophageal sphincter Gastric acid
(LES) Pepsin
Esophageal acid clearance Bile salts
Gastric emptying
Mucosal resistance
Factors That May Contribute to Heartburn
Dietary Medications Quinidine
Alcohol (ethanol) Alpha-adrenergic antagonists TCAs
Caffeinated beverages Anticholinergic agents Tetracycline
Carbonated beverages Aspirin/NSAIDs Theophylline
Chocolate Barbiturates Zidovudine
Citrus fruit or juices Benzodiazepines Diseases
Fatty foods Beta2-adrenergic agonists Motility disorders (e.g., gastroparesis)
Garlic or onions Bisphosphonates PUD
Mint (e.g., spearmint, peppermint) Calcium channel blockers Scleroderma
Salt and salt substitutes Chemotherapy Zollinger-Ellison syndrome
Spicy foods Clindamycin Other
Tomatoes/tomato juice Dopamine Genetics
Lifestyle Doxycycline Pregnancy
Exercise Estrogen
Obesity Iron
Smoking (tobacco) Narcotic analgesics
Stress Nitrates
Supine body position Progesterone
Tight-fitting clothing Prostaglandins
Alarm Symptoms

Result from complications associated with GERD:

 Dysphagia (difficulty in swallowing)

 Odynophagia (painful swallowing)

 Signs of upper GI bleeding

 Chest pain (could be ischemic heart disease)

 Nausea and vomiting

 Other atypical manifestations (e.g., asthma) result from the aspiration of refluxate
into the upper airways and lungs.
Alarm symptoms
 GERD-related chest pain is usually substernal, but it may mimic ischemic
cardiac pain by radiating to the back, neck, jaw, or arms.

 It often worsens after meals and during periods of emotional stress and
may awaken the patient from sleep.

 Severe, crushing chest pain—especially if accompanied by nausea,

vomiting, sweating, and shortness of breath—suggests ischemic pain and
possibly myocardial infarction and should be considered a medical
emergency.

 However, the "typical" crushing chest pain usually associated with a

myocardial infarction is more common in men than in women.
Goals of Therapy

 Relief symptoms

 Prevent meal- or exercise-related symptoms

 Improve quality of life

 Relief abdominal discomfort

◦ The primary goal of self-treatment of dyspepsia
Exclusions for Self Treatment

 Frequent heartburn > 3  Heartburn and dyspepsia

months that occur when taking a
prescription H2RA or PPI
 Heartburn while taking
recommended dosages of  Severe heartburn and
OTC H2RA or PPI dyspepsia

 Heartburn that continues  Nocturnal heartburn

after 2 weeks of treatment
with an OTC H2RA or PPI
 Difficulty or pain on
swallowing solid foods
Exclusions for Self Treatment
 Vomiting up blood or black
material or passing black
stool
 Chronic hoarseness,
wheezing, coughing, or
choking
 Unexplained weight loss
 Continuous N/V, or diarrhea
 Chest pain accompanied by
sweating, pain radiating to
shoulder, arm, neck, or jaw,
and shortness of breath
 Pregnancy
 Nursing mothers
 Children < 2 yrs (for
antacids), or< 12 yrs (for
H2RA),or < 18 yrs (for
PPIs)
General Treatment Approach

 Antacids and nonprescription H2RAs should be recommended

for individuals with mild infrequent heartburn and dyspepsia.

 Antacids are advantageous because they provide rapid relief of

symptoms
◦ But relief is brief when taken on an empty stomach.

 A nonprescription H2RA is preferred to an antacid when

individuals require more prolonged relief of symptoms.
General Treatment Approach

 H2RAs may also be used to prevent heartburn when given 30

minutes to 1 hour prior to exercise or a heavy or spicy meal known
to cause symptoms

 When rapid relief and longer duration are desirable  taking an

antacid initially followed by an H2RA or taking a combination
antacid/H2RA product may be recommended

 Nonprescription PPIs are the drugs of choice for treating frequent

heartburn or when patients do not respond to nonprescription H 2RAs

 Patients should not exceed 14 days of self-treatment

Nonpharmacologic Therapy

 Avoid foods and beverages  Eat smaller meals

that precipitate heartburn  Smoking cessation
 Caffeine and alcohol
 Weight loss (for overweight limitation
patients)  Stress reduction

 Elevate the head of the bed  Wear loose fitting clothing

 Refrain from eating at least

 Avoid bending over
3 hours before going to bed
or lying down
Pharmacologic Therapy

Antacids
 Relieve heartburn and dyspepsia by neutralizing gastric acid

 Nonprescription antacid products contain at least one of the

following salts:

◦ Magnesium (hydroxide, carbonate, or trisilicate)

◦ Aluminum (hydroxide or phosphate)
◦ Calcium carbonate
◦ Sodium bicarbonate
Pharmacologic Therapy

Antacids
 Minimally absorbed into the systemic circulation

 Individuals should be instructed to take product-specific

recommended dosages at the onset of symptoms

 Dosing may be repeated in 1 to 2 hours, if needed, but should not

exceed the maximum daily dosage for a particular product .

 Antacids provide a rapid onset of symptom relief (5 minutes) but

they have shorter duration of action when taken on empty stomach
(20-30 minutes) .
Pharmacologic Therapy

Antacids
 The duration may be prolonged several hours by taking

antacids after a meal.

 When used in recommended dosages , the available antacids

are interchangeable despite differences in salts and potency.

 Frequent antacid users may need to be switched to a longer-

acting product such as an H2RA, an H2RA plus an antacid, or a
PPI.
Pharmacologic Therapy

Antacids
Side Effects
 Diarrhea
◦ Magnesium salt
 Constipation
◦ Aluminum salt
 Belching and flatulence
◦ Sodium bicarbonate
◦ Calcium carbonate
Drug Interactions
 Decrease absorption of:
 Tetracyclines
 Fluoroquinolones
 Azithromycin
 Digoxin
 Azole antifungals
 Iron
 separate by at least
2 hours
Pharmacologic Therapy

Gaviscon®
 Mixture of:
Alginic Acid
◦ Calcium carbonate  Reacts with sodium bicarbonate
◦ Sodium bicarbonate To form a viscous layer of
◦ Magnesium carbonate sodium alginate that floats on
◦ Aluminium hydroxide the surface of gastric contents
◦ Alginic acid
 forming a protective barrier
against esophageal irritation
Pharmacologic Therapy

Histamine2-Receptor Antagonists (H2RAs)

 Cimetidine
Mechanism of Action
 Inhibit histamine on histamine2
 Ranitidine
receptor of the parietal cell
 Famotidine   decrease fasting and food-
stimulated gastric acid secretion and
 Nizatidine gastric volume

 H2RAs are effective in relieving

fasting and nocturnal symptoms
 Pharmacologic Therapy

Histamine2-Receptor Antagonists (H2RAs)

Trade
Primary Ingredients Adult Dosage (maximum daily dosage)
Name
H2RA Products (Adults/Children ≥ 12 Years)
Tagamet® Cimetidine 200 mg 1 tablet with a glass of water (2
tablets)
Axid® Nizatidine 75 mg Same as above
Pepcid® Famotidine 10 mg Same as above
Pepcid® Famotidine 20 mg Same as above
Zantac® Ranitidine 75 mg Same as above
Zantac® Ranitidine 150 mg Same as above
Pharmacologic Therapy

Histamine2-Receptor Antagonists (H2RAs)

 May be used at the onset of symptoms or 30 minutes to 1 hour
prior to an event (e.g., meal or exercise) in which heartburn is
anticipated

 When rapid relief of episodic heartburn and longer duration of

action is desirable , patients should be advised to take antacids
initially followed by H2RAs or use a combination of
antacid/H2RA product.
Pharmacologic Therapy

 When used in recommended doses and comparative dosages ,

H2RAs are considered interchangeable despite differences in
onset, side effects and Dx/Dx interaction

 Tolerance to the gastric antisecretory effect may develop when

H2RAs are taken daily (versus as needed)
◦  diminished efficacy

  it is preferable to take an H2RA on an as-needed basis

rather than continuously every day
Pharmacologic Therapy

Histamine2-Receptor Antagonists (H2RAs)

Side Effects Drug Interactions
 Headache
Decrease absorption of drugs
 Diarrhea
that requires acidic medium
 Constipation
e.g., iron, azole antifungals
 Dizziness

 Drowsiness
Cimetidine is a potent inhibitor
of several CYP450 isoenzymes
 a lot of drug-drug
interactions
Pharmacologic Therapy

Histamine2-Receptor Antagonists (H2RAs)

 Lower doses (e.g., famotidine 10 mg bid) should be

recommended for mild infrequent heartburn

 Higher nonprescription doses (e.g., famotidine 20 mg bid)

should be reserved for moderate symptoms

 Consideration should be given to reducing the daily H2RA

dose in patients with renal failure and patients of advanced
age
Pharmacologic Therapy
 Omeprazole
 Lansoprazole
Proton Pump Inhibitors (PPIs)
 Potent antisecretory drugs

 Relieve heartburn and dyspepsia by decreasing gastric acid secretion.

 The onset of symptomatic relief following a PPI is slower than that of

an H2RA , and complete relief of symptoms may take several days

after initiation of therapy.

 However, PPIs provide superior symptomatic relief and a prolonged

duration of action compared with the H2RAs.

 When used to self-treat, the PPI should be limited to a duration of 14

days and re-treatment to every 4 months.
 Pharmacologic Therapy

Proton Pump Inhibitors (PPIs)

Primary Ingredients Adult Dosage (maximum daily dosage)

PPI Products (Adults ≥18 Years)
Omeprazole 1 tablet 30 minutes before morning meal;
magnesium 20.6 mg take daily for 14 days (1 tablet)
Omeprazole 20 mg 1 capsule 1 hour before morning meal; take
Sodium bicarbonate daily for 14 days (1 capsule)
1100 mg
Lansoprazole 15 mg 1 capsule 30 minutes before morning meal;
take daily for 14 days (1 capsule)
Pharmacologic Therapy

Proton Pump Inhibitors (PPIs)

 Not intended for immediate relief of occasional or acute
episodes of heartburn and dyspepsia

 Most effective when taken 30 to 60 minutes before breakfast

Side Effects
 Similar to H RAs
2
 Increased risk of bone fracture
 Clostridium difficile gastroenteritis
with long-term use
Pharmacologic Therapy

Proton Pump Inhibitors (PPIs)

Drug Interactions
 Diazepam, Phenytoin, Warfarin and Digoxin (Increased

bioavailability)

 Decrease methotrexate clearance and increase toxicity

Pharmacologic Therapy

Onset and Duration of Symptomatic Relief with

Nonprescription ­Medications in Relieving Heartburn

Medication Onset of Relief Duration of Relief

Antacids < 5 minutes 20 – 30 minutes
H2RAs 30 – 45 minutes 4 – 10 hours
H2RA + antacid < 5 minutes 8 – 10 hours
PPIs 2 – 3 hours 12 – 24 hours
Pharmacologic Therapy

Bismuth Subsalicylate (BSS)

 Indicated for:

◦ Heartburn Turns stool and tongue

 Uncertain how BSS black
relieves heartburn
Dark-colored stools may
◦ Upset stomach
◦ Indigestion be interpreted as an upper
GI bleed
◦ Nausea
 prompting needless
◦ Diarrhea
medical procedures
Special population

Breast-feeding

 Magnesium hydroxide and aluminum hydroxide are not

secreted in breast milk in substantial amounts:
→Recommended.

 Ranitidine and Famotidine are less concentrated in breast milk

→Recommended.

 Omeprazole: Insufficient data

Special population

 Patients with renal impairment: caution when prescribing

H2RAs and Antacids.

 Pediatric population < 12 years should be referred to a

primary care years of age.
 Nonprescription PPI should be used for patient ≥

 Pregnant women with frequent and moderate to severe

heartburn should be referred to a primary care for evaluation
although calcium and magnesium antacids as well as H2RAs
are listed as category B.
Key Points for Heartburn and Dyspepsia

 Limit the self-treatment of heartburn and dyspepsia to mild or moderate

symptoms

 Refer patients with alarm symptoms for further evaluation

 GERD-related chest pain may mimic ischemic cardiac pain radiating to

the back , neck, jaw or arms. Because it is not possible clinically to
differentiate cardiac pain from non cardiac pain , patients who complain
from chest pain should be referred to the emergency department.

 Advise individuals with self-treatable symptoms that if symptoms

worsen or recur after 14 days of effective self-treatment  they should
contact their PCP
Key Points for Heartburn and Dyspepsia

 H2RAs are indicated for mild and infrequent heartburn or

dyspepsia

 Combining an antacid with an H2RA provides immediate

relief of heartburn and a longer duration of action

 PPIs are indicated for the treatment of frequent heartburn and

are not intended for immediate relief of infrequent symptoms

 Antacids provide temporary relief for mild and infrequent

heartburn and dyspepsia