CLINICAL PHARMACY & Chapter 12: Peptic ulcer disease

PHARMCOTHERAPY 1 Ms. Neri Margaret Fabillo

AY 2022-2023 MM/DD/YYYY
2nd Semester

I. PATHOPHYSIOLOGY
OUTLINE
1 Epidemiology 5. Investigation ● Peptic ulcer
2. Pathogenesis 6. Treatment → a condition in which there is a discontinuity in the entire
3. Clinical Manifestation 7. Ulcer-healing drugs thickness of the gastric or duodenal mucosa that persists as
a result of acid and pepsin in the gastric juice
4. Patient Assessment 8. Patient Care
→ Infection by H. pylori, a spiral bacterium of the stomach,
Note: For long outlines, use two columns to save space for main
remains an important epidemiological factor in causing peptic
content. For short outlines, just merge the two columns.
ulcer
LEARNING OBJECTIVES A. PATHOGENESIS
• The two main types of peptic ulcer disease are those
associated with Helicobacter pylori and those associated with ● Two common forms of peptic ulcer disease
non-steroidal anti-inflammatory drugs (NSAIDs) and aspirin. → Helicobacter pylori
• Ulcer-like dyspepsia does not correlate with diagnosis of ▪ Ninety-five percent or more of duodenal ulcers and
peptic ulcer. 80–85% of gastric ulcers are associated with H. pylori.
• Uninvestigated dyspepsia without alarm symptoms may be ▪ The underlying pathophysiology associated with H. pylori
treated empirically without an endoscopic diagnosis. infection involves the production of cytotoxin-associated
• An H. pylori test and treat strategy means it is unknown if the gene A (CagA) proteins and vacuolating cytotoxins, such
patient has an ulcer. as vac A, which activate the inflammatory cascade.
• Triple therapy with a proton pump inhibitor (PPI), ▪ High acid content in the proximal duodenum leads to
clarithromycin and amoxicillin twice daily for 7 days is metaplastic gastric-type mucosa, which provides a niche
currently the recommended first-line H. pylori eradication for H. pylori infection followed by inflammation and ulcer
regimen. formation.
• Patient adherence influences the success of H. pylori → Non-steroidal anti-inflammatory drugs
eradication therapy. ▪ Three patterns of mucosal damage are caused by
• H. pylori eradication therapy does not have a role in the NSAIDs
management of gastro-oesophageal reflux disease (GORD). − Superficial erosions and haemorrhages
Its benefit in the management of functional dyspepsia is o Weak acid NSAIDs, such as acetylsalicylic acid, are
small. concentrated from the acidic gastric juice into
• Associated risks of Clostridium difficile infection, pneumonia mucosal cells, and may produce acute superficial
and osteoporosis have led to judicious use of PPIs. erosions via inhibition of COX and by mediating the
• Patients who need to continue NSAID therapy are the only adherence of leucocytes to mucosal endothelial
patients with peptic ulcer disease in whom continued cells.
ulcer-healing therapy is necessary after the ulcer has healed o Enteric coating may prevent this superficial damage
and H. pylori has been eradicated. but does not demonstrate any clinical benefit in
• Upper gastro-intestinal symptoms in NSAID users do not terms of reduction of gastro-intestinal bleeding or
correlate well with presence or absence of peptic ulcers. ulceration
• The risk of ulcers associated with NSAID use is common to − Silent ulcers detected at endoscopy
all non-specific NSAIDs and is dose dependent. The risk is o All NSAIDs share the ability to inhibit COX.
maintained during treatment and decreases once treatment is o The presence of NSAID-induced ulcers does not
stopped. correlate with abdominal pain and NSAIDs
• Risk factors for NSAID-induced gastro-intestinal complications themselves often mask ulcer pain.
include previous history of peptic ulcer or gastro-intestinal o Approximately 20% of patients taking NSAIDs
bleeding, age >65, concomitant use of aspirin, anticoagulants experience symptoms of dyspepsia but symptoms
or corticosteroids. correlate poorly with the presence of mucosal
• Adding a PPI to non-specific NSAIDs provides a similar damage
reduction in risk of gastro-intestinal toxicity to that offered by − Ulcers causing clinical symptoms complications
cyclo-oxygenase-2 (COX-2) inhibitors alone. o Ulcers and ulcer complications occur in
• Enteric coating or taking them with food does not reduce approximately 4% of NSAID users every year.
the risk of upper gastro-intestinal bleeding associated with o Patients taking NSAIDs have a four-fold increase in
NSAIDs and low-dose aspirin. risk of ulcer complications compared with non-users.
• Adding a PPI to aspirin is associated with lower risk of B. CLINICAL MANIFESTATION
recurrent gastro-intestinal bleeding than clopidogrel alone. ● Upper abdominal pain occurring 1–3 h after meals and relieved
• Concomitant PPI therapy may decrease clopidogrel activity by food or antacids is the classic symptom of peptic ulcer
through competitive hepatic metabolism; the combination disease.
is not recomm ● Anorexia, weight loss, nausea and vomiting, heartburn and
eructation can all occur with peptic ulcer disease.
● Patients with predominant symptoms of heartburn are likely to
have GERD.
● Complications of peptic ulcer disease may occur with or without
previous dyspeptic symptoms.

CLINPHARM Group 2 - 2A : Andres, Balando, Bucane, Canillas, Galangue,Gonzales, Llarenas, Mengote, Muncada, Pabia, Pazon, Rosales, Samante, Severino, Vierras, Yee 1 of 5
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● In the elderly, the presentation is more likely to be silent and
gastrointestinal bleeding may be the first clinical sign of disease.
● Peptic ulcer bleeding is the most frequent and severe
complication of peptic ulcer disease.
C. DIFFERENTIAL ANALYSIS
● The following conditions can present with symptoms similar to
peptic ulcer disease:
→ Gastritis
▪ an inflammatory process of the gastric mucosa from
immune-mediated or infectious etiology presenting with
upper abdominal pain and nausea.
▪ Clinical presentation is very similar to that of peptic ulcer
disease
→ Gastroesophageal reflux disease (GERD)
▪ patients usually describe a burning sensation in the
epigastrium and lower retrosternal area, excessive
salivation, or intermittent regurgitation of food material.
→ Gastric cancer
▪ apart from abdominal pain, patients usually describe
alarm symptoms like weight loss, melena, recurrent
vomiting, or evidence of malignancy elsewhere in case of
metastasis.
→ Pancreatitis
▪ epigastric or right upper quadrant pain that is more
persistent and severe, worse in the supine position, and
patients usually have a history of alcoholism or gallstones.
▪ Elevated serum amylase and lipase are useful in the
diagnosis
→ Biliary colic
▪ intermittent, severe deep pain in the right upper quadrant
or epigastrium precipitated by fatty meals.
→ Cholecystitis
▪ right upper quadrant or epigastric pain that usually lasts
for hours and is exacerbated by fatty meals and is
associated with nausea and vomiting.
▪ Fever, tachycardia, positive Murphy sign, leukocytosis,
and abnormal liver functions help further distinguish this
from biliary colic.
D. LABORATORY TESTS
ENDOSCOPY
● the investigation of choice for diagnosing peptic ulcer.
● The procedure is sensitive, specific, and safe.
● invasive and expensive
● more accurate and almost always preferred.
● Endoscopic investigation should be undertaken in patients
with alarm features and in those patients over 55 years who
present with unexplained or persistent symptoms of dyspepsia.
● Wireless capsule endoscopy
→available to investigate NSAID-induced ulceration of the
small intestine causing gastro-intestinal haemorrhage
→preferable to radiological imaging.
RADIOLOGY
● Double-contrast barium radiography- should detect 80% of
peptic ulcers.
● Gastrograffin® meal is used to diagnose peptic perforation in
patients presenting with an acute abdomen, if a plain abdominal
X-ray is not diagnostic.
H. PYLORI DETECTION (NON-INVASIVE TESTS)
● Serological tests
→ to detect antibodies
→ not recommended as they are inaccurate
CLINPHARM Title of Lecture
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→ based on the detection of anti-H. pylori IgG antibodies
● Urea breath tests
→ preferable and more convenient
→ have a sensitivity and specificity over 90%
→ accurate for both initial diagnosis and confirmation of
eradication.
→ based on the principle that urease activity in the stomach of
infected individuals hydrolyses urea to form ammonia and
carbon dioxide.
→ contains carbon-labelled urea
● Stool antigen tests
→ uses an enzyme immunoassay to detect H. pylori antigen in
stool.
→ also has a sensitivity and specificity over 90%
→ can be used in the initial diagnosis and also to confirm
eradication.
E. DRUG OF CHOICE
PROTON PUMP INHIBITORS (PPIs)
● PPIs are inactive prodrugs that are carried in the bloodstream to
the parietal cells in the gastric mucosa.
● weak bases and therefore have a high affinity for acidic
environments.
● PPIs require an enteric coating to protect them from
degradation in the acidic environment of the stomach.
Examples: Omeprazole, Esomeprazole, Lansoprazole,
Pantoprazole and rabeprazole
MOA: Control gastric acid secretion by inhibition of gastric H+, K+-
ATPase
ADR: Diarrhea, Headaches, Abdominal pain, Nausea, fatigue, and
dizziness, and ↓ bone density and ↑ risk of hip fractures (long term
use)
H2-RECEPTOR ANTAGONISTS
● PPIs are less effective than PPIs in eradication regimens, in
treating ulcers when NSAIDs are continued, and in prophylaxis
of NSAID-induced ulcers.
● effectively heal ulcers in patients who discontinue their NSAID
● Their main role is in the empirical management of dyspepsia
symptoms.
● second-line treatment of heartburn in pregnancy
Examples: Cimetidine, Ranitidine, famotidine, Nizatidine
MOA: Competitively block the histamine receptors in gastric
parietal cells.
ADR: Diarrhea, Headaches, Abdominal pain, and Confusion
F. ALTERNATIVE DRUG TREATMENT
SUCRALFATE
→ is the aluminium salt of sucrose octasulphate.
→ weak antacid
→ Has mucosal protective effects
→ It is capable of adsorbing bile salts.
→ not effective in the treatment and prevention of
NSAID-related gastric ulcers.
→ prophylaxis of stress ulceration
MOA: Forms a sticky viscid gel that adheres to ulcer surface
providing physical protection
ADR: Constipation, aluminium toxicity
G. OTHER DRUG THERAPIES & MODE OF ACTION
BISMUTH CHELATE
● Has been included in antacid mixtures for many decades but fell
from favour because of its neurotoxicity.
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● Bismuth chelate is a relatively safe form of bismuth that has
ulcer-healing properties comparable to those of H2 PHYSICAL
-antagonists. ● Epigastric pain
● Duodenal ulcer pain
● Bismuth is toxic to H. pylori and was one of the first agents to be ● Chest discomfort
used to eradicate the organism and reduce ulcer recurrence. ● Dyspepsia

● MOA: Pain Management Strategies

→ Its mode of action is not clearly understood but it is thought ● Dietary Modifications (Avoid spicy food , eat smaller meals, and
to have cytoprotective properties. avoid caffeine)
● Relaxation Techniques (Yoga and deep breathing)
● ADVERSE DRUG REACTIONS ● Medications (PPIs and antibiotics)
→ The most commonly reported events are:
▪ Nause PSYCHOLOGICAL
▪ Vomiting ● Anxiety
▪ Blackened tongue ● Depression
▪ Dark feces ● Fear
→ Bismuth may accumulate in patients with impaired renal
function. Counseling & Support
● For patient and family
ANTACIDS
● Used in the symptomatic relief of dyspepsia, in particular Cognitive Behavioral Therapy
symptoms associated with GORD. ● Identify and modify unhelpful thoughts

● They have a role in the management of symptoms which SOCIAL

sometimes remain for a short time after H. pylori eradication of ● Financial Burden
uncomplicated duodenal ulcer. ● Caregiver Burden
● Relationships
● Provide immediate symptom relief and a more rapid response is
achieved with liquid preparations. Lifestyle Changes
● Reduce stress
● They have a limited duration of action and need to be taken ● Quit smoking
several times a day, usually after meals and at bedtime. ● Avoid alcohol
● Administration should be separate from drugs with potential for Provide Education & Management
chelation and also pH-dependent controlled-release products. ● Reduce the burden of caregivers
● The choice of antacid:
SPIRITUAL
→ Aluminium-based products
▪ Adverse Effect: Constipation ● Hope
→ Magnesium-based products ● Suffering
▪ Adverse Effect: Diarhhea ● Religiosity

Note: Although these are termed ‘non-absorbable’, a proportion Spiritual Activities

of aluminium and magnesium is absorbed and the potential for ● Prayer
toxicity exists, particularly with coexistent renal failure. ● Meditation

● Calcium-based products are unsuitable as calcium Practice Self-Care & Self-Compassion

stimulates acid secretion. Antacids containing sodium
bicarbonate are unsuitable for regular use because they J. GOAL OF THERAPY
deliver a high sodium load and generate large quantities of
carbon dioxide. ● Relieve Symptoms
● Accelerate Healing
● Products containing sodium alginate with a mixture of ● Improve Pain
antacids are effective in relief of symptoms in GORD but are ● Avoid Side Effects
not particularly effectual antacids. ● Reduce Cost
● Prevent Recurrence
H. ALTERNATIVE TREATMENT STRATEGIES
K. POSSIBLE DRUG INTERACTIONS
● High-fiber food:
→ Apple DRUG INTERACTIONS FOR PROTON PUMP
→ Pears INHIBITORS
→ Oatmeal ● Omeprazole inhibits CYP2C9 and 2C19
→ Effect: Omeprazole 40mg daily can decrease the
I. PALLIATIVE CARE clearance of phenytoin

● Palliative care is the prevention and relief of suffering of any ● Lansoprazole is a weak inducer of CYP1A2 and concurrent
kind - experienced by adults and children living with life-limiting administration results in increased theophylline clearance
health problems.

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DRUG INTERACTIONS FOR H2-RECEPTOR
ANTAGONISTS
● Cimetidine inhibits the activity of cytochrome P450 and
consequently retards oxidative metabolism of some drugs. This
interaction is potentially important for drugs with a narrow
therapeutic index.
→ Effect:
▪ The clearance of theophylline is reduced to about 40%
of normal, and raised plasma levels occur as a result.
▪ The metabolism of a number of benzodiazepines,
including diazepam, flurazepam and triazolam, is
impaired and levels are raised.
▪ The metabolism of (R)-warfarin is affected to a greater
degree than that of (S)-warfarin.
− As the (S) enantiomer is the more potent, the
pharmacodynamic effects of the interaction may be
modest, although the plasma warfarin concentrations
may be increased.
− Other H2 -antagonists should be used in patients who
are difficult to stabilise on warfarin or for whom
frequent monitoring is not feasible.
● Misoprostol should not be used in pregnant women, and
women of childbearing age should be warned appropriately
● Patients with diagnosed peptic ulcer disease need to be
educated about the current principles of therapeutic
management determined by the diagnosis and, if appropriate,
the balanced risks associated with continued aspirin or NSAID
therapy.
● Uncomplicated disease requires a short course of
treatment which may or may not include eradication of H.
pylori. Patients need to know the importance of adherence to
eradication therapy for successful treatment and to avoid
development of resistance to antibiotics.
● Previous adverse reactions should be established; for
example, patients who are sensitive to penicillin need an
eradication regimen which does not include amoxicillin.
● Patients should be warned of the specific side effects to be
expected and advised what to do should they experience any
of these effects.

● All acid-suppressing drugs potentially decrease the
absorption of drugs such as ketoconazole and other
pH-dependent controlled-release products by increasing gastric
pH.
DRUG INTERACTIONS FOR SUCRALFATE
● Sucralfate may bind to other agents in the gastro-intestinal tract
and reduce the absorption of other drugs
→ Should be taken at least 2h following other medicines.
● Patients taking metronidazole must avoid alcohol as they
might have a disulfiram-like reaction with sickness and
headache.
● Patients need to know how their therapy will be followed
up. In most patients, a single treatment course is required and
there is no need for maintenance therapy unless they require
prophylaxis treatment to reduce risks associated with continued
NSAID or low-dose aspirin therapy.

DRUG INTERACTIONS FOR ANTACID M. PATIENT ASSESSMENT

● Toxicity due to increased absorption when taken with
pseudoephedrine and levodopa. DYSPEPSIA
● In functional dyspepsia, symptom control is poor but a small
L. PATIENT EDUCATION and significant benefit of eradication treatment has been shown.
Acid suppression is only of benefit in a small proportion of
● Patients who present with symptoms of dyspepsia should be patients with functional dyspepsia.
assessed in terms of risk of serious disease.
● Symptom subgroups such as ulcer, reflux and dysmotility type
● Patients with predominant reflux-like symptoms are likely to may be useful in identifying the predominant symptom subgroup
respond to antacid/alginate medicines. In those with to which a patient belongs.
reflux-like symptoms, lifestyle should be assessed as weight
loss is known to improve reflux symptoms in obese patients and
raising the head of the bed may improve nocturnal symptoms of
heartburn.

● Symptoms of dyspepsia are associated with many medicines

including aspirin, NSAIDs and corticosteroids. Other agents are
associated with gastrooesophageal reflux and include those
with antimuscarinic effects.

● Patients should be advised to seek the pharmacist's advice

when purchasing over-the-counter analgesic preparations.

● Patients with risk factors for peptic ulcer disease should be

advised to avoid over-the-counter aspirin and NSAIDs and to
use paracetamol-based products.
→ Taking aspirin or NSAIDs with or after food may decrease the
risk of dyspepsia symptoms but does not decrease the risk
of ulcer complications.

● Before prescribing NSAID or aspirin therapy, patients should be ● In some cases, medications may be the cause of dyspepsia
assessed in terms of both cardiovascular and gastro-intestinal and should be reviewed.
risk.

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 ● Patients with iron-deficiency anaemia following a bleeding
ulcer may be prescribed oral iron therapy.
→ Iron preparations are best absorbed from an empty stomach
but if gastric discomfort is felt, the preparation should be
taken with food.

● Common therapeutic problems in the treatment of peptic ulcer

disease are summarised in Table 12.4 of page 179 to 180 in
book.

● Patients at any age who present with alarm features should be

referred for endoscopic investigation. These groups of patients
are at a higher risk of underlying serious disease such as
cancer, ulcers or severe oesophagitis.

● Referral is also recommended for patients over the age of 55 if

symptoms are unexplained or persistent despite initial
management.

● Malignant disease is rare in young people and in those without

alarm features.

● Patients with predominant reflux-like symptoms are likely to

respond to acid-suppressing therapy and one month's
treatment of standard dose of PPI should be given in patients
whose symptoms persist despite antacid and lifestyle
adjustment.

● Eradication of H. pylori is not beneficial in GORD.

● In those patients who do not have reflux-like dyspepsia, testing

for the presence of H. pylori is recommended.

● Eradication treatment should be prescribed for those who test

positive and empirical acid suppression for those who test
negative. The small proportion of patients with symptoms due to
ulcers should be cured.

N. PATIENT MONITORING

● Patients with complicated ulcers or those who continue to

have symptoms will receive a urea breath test and/or an
endoscopy to confirm successful eradication of H. pylori.

● Following eradication therapy, some patients continue to

experience symptoms of abdominal pain. Patients should be
reassured that these symptoms will resolve spontaneously, but
if necessary an antacid preparation can be recommended to
relieve symptoms until review.

● Patients receiving treatment for NSAID-induced ulceration

should continue their ulcer-healing therapy for 4 weeks.

CLINPHARM Title of Lecture 5 of 5

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