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Heartburn

Lecture 5

Dr Wejdan Shroukh
Slides prepared by MSc. Rasha Maraqa

Heartburn
Is a form of indigestion (dyspepsia) also more formally
known as gastro-esophageal reflux disease (GERD).

Symptoms of heartburn are caused when there is reflux of

gastric contents, particularly acid, into the esophagus,
which irritate the sensitive mucosal surface (esophagitis).

Patients will often describe the symptoms of heartburn –

typically a burning discomfort/pain felt in the stomach,
passing upwards behind the breastbone (retrosternal).

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Heartburn
• What is the difference between Heartburn (‫ )الحرقة‬and indigestion (‫?)عسر الهضم‬

Heartburn is another term for Gastro-esophageal acid reflux, which affects the esophagus lining.
When the acid made by your stomach escapes or regurgitates back into your esophagus, you receive
the burning sensation close to your heart widely known as heartburn.
Either your stomach makes too much acid, or the mechanism keeping the acid in your stomach after
you eat, a muscular valve called the lower esophageal sphincter, is not fully closing after a meal.

Indigestion is medically known as dyspepsia, which affects the stomach lining. It occurs in the upper
abdomen just under the breast bone. A number of things can cause indigestion and it usually causes
sensations of discomfort, low-grade pain or nausea.

Indigestion is typically chronic and occurs off and on for most individuals. While heartburn can cause
you to awaken at night with pain or discomfort, indigestion usually does not awaken you.

Heartburn
What you need to know/ 1. Age
The symptoms of reflux and esophagitis occur more commonly in patients aged over 55 years.

Heartburn is not a condition normally experienced in childhood, although symptoms can occur
in young adults and particularly in pregnant women.

Children with symptoms of heartburn should therefore be referred to their doctor.

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Heartburn
What you need to know/ 2. Symptoms
A burning discomfort is experienced in the upper part of the stomach in the midline (epigastrium),
and the burning feeling tends to move upwards behind the breastbone (retrosternal).
The pain may be felt only in the lower retrosternal area or on occasion right up to the throat,
sometimes associated with an acid taste in the mouth.

Heartburn
What you need to know/ 2. Symptoms- Severe Pain

Sometimes the pain can come on suddenly and severely and

even radiate to the back and arms.

In this situation differentiation of symptoms is difficult as the

pain can mimic a heart attack and urgent medical referral is
essential.

Sometimes patients who have been admitted to hospital

apparently suffering a heart attack are found to have
esophagitis instead.

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Heartburn
What you need to know/ 2. Symptoms- Difficulty Swallowing (Dysphagia)

Must always be regarded as a serious symptom. The difficulty may be

either discomfort as food or drink is swallowed or a sensation of food
or liquids sticking in the esophagus.

Both require referral.

It is possible that the swallowing discomfort may be secondary to

inflammation of the esophagus (esophagitis) due to acid reflux,
especially when it occurs while swallowing hot drinks or irritant fluids
(e.g. alcohol or fruit juice).
A history of a sensation that food sticks as it is swallowed or that it does
not seem to pass directly into the stomach is an indication for immediate
referral.
It may be due to obstruction of the esophagus, for example, by a tumor,
or can result from severe esophagitis with inflammation and narrowing.

Heartburn
What you need to know/ 2. Symptoms- Regurgitation

Happens when a mixture of gastric juices, and sometimes undigested food, rises back up the
esophagus and into the mouth.

Regurgitation can be associated with difficulty in swallowing.

It occurs when recently eaten food sticks in the esophagus and is regurgitated without passing into the
stomach.

This is due to a mechanical blockage in the esophagus (cancer as well as by less serious conditions
such as an esophageal stricture).

A stricture is caused by long-standing acid reflux with esophagitis. The continual inflammation of the
esophagus causes scarring.

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Heartburn
What you need to know/ 2. Symptoms- Regurgitation

Scars contract and can therefore cause narrowing of the esophagus.

This can be treated by dilatation using a fiber-optic endoscope.

However, medical examination and further investigations are

necessary to determine the cause of regurgitation.

Heartburn
What you need to know/ 3. Aggravating Factors

Heartburn is often brought on by bending or lying down.

It is more likely to occur in those who are overweight and can be aggravated by a recent
increase in weight.

It is also more likely to occur after a large meal.

Alcohol and smoking are known to cause or aggravate heartburn.

Stress is also a factor in the condition.

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Heartburn
What you need to know/ 3. Aggravating Factors
Certain medication may also worsen the heartburn: calcium
channel blockers, anticholinergics (particularly those with
more pronounced anticholinergic effects such as
amitriptyline), theophylline and nitrates.

Caffeine in coffee, tea or soft drinks such as cola, and in some

analgesics and cold remedies.

The reason for this is that these types of drugs cause

relaxation of the lower end of the esophagus.

This normally acts as a sphincter, allowing food into the

stomach, but stopping the acid contents of the stomach going
up into the esophagus when the stomach contracts. The lining
of the stomach is resistant to the irritant effects of acid,
whereas the lining of the esophagus is readily irritated by acid.

Heartburn
What you need to know/ 3. Aggravating Factors
NSAIDs will make the inflammation in esophagitis worse. Aspirin or oral corticosteroids (e.g.
prednisolone) can also aggravate esophagitis.

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Heartburn
What you need to know/ 3. Aggravating Factors
Bisphosphonates (alendronate, for example), taken for osteoporosis, can cause severe esophagitis, and
this is the reason it is important that people drink water and stay upright after taking them.

The hydrophobic properties of the phospholipids prevent gastric acid from reaching the
epithelium. Bisphosphonates act as topical irritants to the GI lining resulting in chemical esophagitis.

Phosphatidylcholine (PC) is one of the phospholipids responsible for the hydrophobic properties of the
bilayer. PC has demonstrated an ability to create a protective environment on both inert and biological
surfaces and protect GI cells from irritating agents.

Both bisphosphonates and PC are similar in size and molecular structures - with a negatively charged
phosphate group and a positively charged nitrogen group connected by a 2-carbon chain. The
comparable molecular composition of bisphosphonates and zwitterionic phospholipids creates
competitive binding on the mucosal layer. When bisphosphonates bind, this prevents PC or other
protective phospholipids from binding and producing the hydrophobic barrier that protects the
epithelial lining from gastric acid.

Heartburn
What you need to know/ 4. Duration

If symptoms have not responded to treatment after 1 week, the patient should see a doctor.

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Heartburn
What you need to know/ 5. When to Refer
Failure to respond to medication within one week.

Related to prescribed medication

Pain radiating to arms

Difficulty in swallowing

Regurgitation

Long duration

Increasing severity

Children

Heartburn
What you need to know/ 6. Management

If the patient is overweight, weight reduction should be advised.

There is some evidence that weight loss reduces symptoms of heartburn.

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Heartburn
What you need to know/ 6. Management

Small meals, eaten frequently, are better than large

meals, as reducing the amount of food in the
stomach reduces gastric distension, which helps to
prevent reflux.

Gastric emptying is slowed when there is a large

volume of food in the stomach; this can also
aggravate symptoms.

High-fat meals delay gastric emptying.

The evening meal is best taken several hours before

going to bed.

Heartburn
What you need to know/ 6. Management

Certain postures can provoke symptoms.

It is better to squat rather than bend down.

Since the symptoms are often worse when the patient lies down, there is evidence that raising
the head of the bed can reduce both acid clearance and the number of reflux episodes. Using
extra pillows is often recommended.

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Heartburn
What you need to know/ 6. Management

d. Proton
c. H2
a. Antacids b. Alginates pump
antagonists
inhibitors

Heartburn
a. Antacids b. Alginates

An alginate is derived from seaweed.

A group of medicines which help to
Alginate-based products provide a physical barrier
neutralize the acid content of your
and work by forming a neutral floating gel or raft
stomach (a protective barrier) on top of the stomach to
prevent stomach contents, including pepsin, from
backing up into the esophagus and airways.

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Acid Reducers
a. Antacids b. Alginates

Acid Reducers
a. Antacids

Some alginate-based products contain Sodium Bicarbonate

In addition to its antacid action, causes the release of carbon dioxide in

the stomach, enabling the raft to float on top of the stomach contents.

Preparations that are high in sodium should be avoided by those who are
on a sodium-restricted diet (e.g. those with heart failure or kidney).

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Acid Reducers
a. Antacids

Calcium carbonate acts quickly, has a prolonged action and is a

potent neutralizer of acid.

If taken over long periods at high doses, can cause hypercalcaemia

and so should not be recommended for long-term use.

Calcium carbonate and sodium bicarbonate can, if taken in large

quantities with a high intake of milk, result in the milk-alkali
syndrome. This involves hypercalcaemia, metabolic alkalosis and
renal insufficiency; its symptoms are nausea, vomiting, anorexia,
headache and mental confusion.

Acid Reducers
a. Antacids

Aluminum-based antacids are effective, but they tend to be

constipating. The use of aluminum antacids is best avoided in anyone
who is constipated and in elderly patients who have a tendency to
constipation.

Magnesium salts are more potent acid neutralizers than aluminum

salts. They tend to cause osmotic diarrhea as a result of the
formation of insoluble magnesium salts and are useful in patients
who are constipated or prone to constipation.

Combination products containing aluminum and magnesium salts

may cause less bowel disturbance and are therefore valuable
preparations for recommendation by the pharmacist.

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Acid Reducers
- Sucralfate “ a complex of aluminium hydroxide and sucrose octasulfate. It dissociates
in the acid environment of the stomach to its anionic form, which binds to the ulcer
base. This creates a protective barrier to pepsin and bile and inhibits the diffusion of
gastric acid”.

-Indicated in the short-term (up to 8 weeks) treatment of active duodenal ulcer.

Acid Reducers
b. H2 antagonists

(Enterochromaffin-like cells)

•Selectively block H2 receptors located on

the parietal cells.

•Prevents the release of gastrin, a hormone

that causes local release of histamine (due
to stimulation of histamine receptors),
ultimately blocking the production of
hydrochloric acid.

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Acid Reducers
b. H2 antagonists

Indications:

• Duodenal ulcer
• Gastric ulcer
• GERD
• Esophagitis & accompanying symptoms due to GERD
• Eradication of H.pylori (off-label use)
• Stress ulcer prophylaxis ( ICU) (off-label use)

b. H2 antagonists

• H2 antagonists are especially effective at inhibiting nocturnal acid secretion (which depends
largely on histamine).

• But they have a modest impact on meal-stimulated acid secretion (which is stimulated by gastrin
and acetylcholine as well as histamine).

• Therefore, nocturnal and fasting intragastric pH is raised to 4–5 but the impact on the daytime,
meal-stimulated pH profile is less.

• Recommended prescription doses maintain greater than 50% acid inhibition for 10 hours; hence,
these drugs are commonly given twice daily.

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Acid Reducers
b. H2 antagonists

The treatment limit (not more than 2 weeks ”tolerance”) is intended to ensure that patients do not
continuously self-medicate for long periods.

Cimetidine is associated with considerably more side effects and drug interactions.

By increasing gastric pH, they can increase the risk of developing Clostridium difficile colitis (diarrhea
several times a day, fever, loss of appetite, feeling sick, tummy pain).

Side effects: HA, diarrhea, nausea and vomiting, gynecomastia*.

* Cimetidine inhibits binding of dihydrotestosterone to androgen receptors, inhibits metabolism of

estradiol, and increases serum prolactin levels.

3. H2 Antagonist
Examples: famotidine, ranitidine, cimetidine

10-20 mg every 12 hours; dose may 75 to 150 mg 30 to 60 minutes before eating
be taken 15-60 minutes before eating food or drinking beverages that cause
foods known to cause heartburn. heartburn (maximum: 2 doses/day).

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Acid Reducers
c. Proton pump inhibitors

(Enterochromaffin-like cells)
Forms a covalent disulfide bond with the
H+/K+-ATPase, irreversibly inactivating the
enzyme.

The drugs have a short serum half-life of

about 1.5 hours, but acid inhibition lasts up
to 24 hours owing to the irreversible
inactivation of the proton pump.

The most effective medicines for the relief of

heartburn.

Acid Reducers
c. Proton pump inhibitors

Indication :
• Active duodenal ulcer, Gastric ulcers: for 4 to 8 weeks.
• Symptomatic GERD (without esophageal lesions): up to 4 weeks.
• Erosive esophagitis: for up to 12 months total therapy (including treatment period of 4 to 8
weeks).
• Helicobacter pylori eradication: for 10-14 days.
• NSAID-induced ulcer treatment (off-label use): 4 to 8 weeks.
• NSAID-induced ulcer prophylaxis (off-label use) for up to 6 months.
• Stress ulcer prophylaxis, ICU patients (off-label use).
• Frequent heartburn (OTC labeling): for 14 days; treatment may be repeated after 4 months if
needed.

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Acid Reducers
c. Proton pump inhibitors

• Six PPIs are available for clinical use: omeprazole, esomeprazole (S-isomer of omeprazole),
lansoprazole, dexlansoprazole, rabeprazole, and pantoprazole.

• In contrast to H2 antagonists, PPIs inhibit both fasting and meal-stimulated secretion because they
block the final common pathway of acid secretion, the proton pump.

• The bioavailability of all agents is decreased approximately 50% by food; hence, the drugs should
be administered on an empty stomach.

• For patients with dysphagia or enteral feeding tubes, capsule formulations (but not tablets) may
be opened and the microgranules mixed with apple or orange juice or mixed with soft foods (eg,
applesauce).

Acid Reducers
c. Proton pump inhibitors

• Esomeprazole, omeprazole, and pantoprazole are also available as oral suspensions.

• Dose reduction is not needed for patients with renal insufficiency or mild to moderate
liver disease BUT should be considered in patients with severe liver impairment.

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Acid Reducers
c. Proton pump inhibitors

• Gastric acid is an important barrier to colonization and infection of the stomach and intestine
from ingested bacteria.

• Increases in gastric bacterial concentrations are detected in patients taking PPIs, which is of
unknown clinical significance.

• Some studies have reported an increased risk of both community-acquired respiratory infections
and nosocomial pneumonia among patients taking PPIs. There is a two- to threefold increased
risk for hospital- and community-acquired Clostridium difficile infection in patients taking PPIs.

• There also is a small increased risk of other enteric infections (eg, Salmonella, Shigella,
Escherichia coli, Campylobacter), which should be considered particularly when traveling in
underdeveloped countries.

Acid Reducers
c. Proton pump inhibitors

• Long-term maintenance therapy with proton-pump inhibitors (PPIs) was shown to be associated
with an increased risk for esophageal cancer.

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4. Proton Pump Inhibitors

Pregnancy Risk Factor:

• Pantoprazole : B
• Lansoprazole : B
• Rabeprazole : B
• Omeprazole and Esomeprazole : C

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4. Proton Pump Inhibitors

Acid Reducers
c. Proton pump inhibitors

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Case Study 1
Mrs. Amy Beston is a woman aged about 50 years who wants some advice about a stomach
problem.

On questioning, you find out that sometimes she gets a burning sensation just above the
breastbone and feels the burning in her throat, often with a bitter taste, as if some food has
been brought back up.

The discomfort is worse when in bed at night and when bending over while gardening.

She has been having the problem for 1 or 2 weeks and has not yet tried to treat it. Mrs.
Beston is not taking any medicines from the doctor.

To your experienced eye, this lady is at least 7–8 kg overweight. You ask Mrs.

Beston if the symptoms are worse at any particular time, and she says they are worst shortly
after going to bed at night.

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Case Study 1/ answer

This woman has many of the classic symptoms of heartburn: pain in the retrosternal region and reflux.
The problem is worse at night after going to bed, as is common in heartburn.

Mrs Beston has been experiencing the symptoms for about 2 weeks and is not taking any medicines
from the doctor.
It would be reasonable to advise the use of an alginate/antacid product about 1 h after meals, and
before going to bed an H2 antagonist or a PPI.

Practical advice could include the tactful suggestion that Mrs Beston’s symptoms would be improved if
she lost weight. If your pharmacy provides a weight management service, you could ask if Mrs Beston
is interested in participating. Alternatively, advice on healthy eating and contact with a local weight
management group could be given. Mrs Beston could also try cutting down on tea, coffee, alcohol and,
if she smokes, stopping. This is a long list of potential lifestyle changes. It might be a good idea to
explain the contributory factors to Mrs Beston and negotiate with her as to which one she will begin
with. Success is more likely to be achieved and sustained if changes are introduced one at a time.
Women going through the menopause are more prone to heartburn, and weight gain at the time of
menopause will exacerbate the problem.

Case Study 2
You have been asked to recommend a ‘strong’ mixture for heartburn for Harry Groves, a local man in
his late 50s who works in a nearby warehouse.
Mr. Groves tells you that he has been getting terrible heartburn for which his doctor prescribed some
mixture about 1 week ago.

You remember dispensing a prescription for a liquid alginate preparation. The bottle is now empty,
and the problem is no better.

When asked if he can point to where the pain is, Mr. Groves gestures across his chest and clenches his
fist when describing the pain, which he says feels heavy.

You ask whether the pain ever moves, and Mr. Groves tells you that sometimes it goes to his neck and
jaw. Mr. Groves is a smoker and is not taking any other medicines. When asked if the pain worsens
when bending or lying down,

Mr. Groves says it does not, but he tells you he usually gets the pain when he is at work, especially on
busy days

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Case Study 2/ answer

This man should see his doctor immediately. The symptoms he has described are not those
that would be typical of heartburn.

In addition, he has been taking an alginate preparation, which has been ineffective.

Mr Groves’ symptoms give cause for concern; the heartburn is associated with effort at work,
and its location and radiation suggest a more serious cause, possibly cardiac.

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