CPP 2 LECTURE PUD

peptic ulcer

describes a condition in which there is a discontinuity in the entire thickness of the gastric or duodenal mucosa that persists as a result of acid and pepsin in the gastric juice

Peptic ulcer disease

refers to a group of ulcerative disorders of the upper gastrointestinal (GI) tract that require acid and pepsin for their formation

dyspepsia

Peptic ulcer disease often presents to clinicians as ______ . However, not all patients with this have peptic ulcer disease

Dyspepsia

is defined as persistent or recurrent pain or discomfort centered in the upper abdomen.

functional dyspepsia, Gastroesophageal disease (GORD) and peptic ulcer.

The most common causes of dyspepsia are (3)

peptic ulcer

accounts for 10–15% of dyspepsia

20

esophagitis accounts for ___% of dyspepsia

endoscopy-negative GERD

60–70% of patients have no obvious abnormality and have functional dyspepsia or __________.

H. pylori and use of aspirin/NSAIDs

There are two common forms of peptic ulcer disease: those associated with (2)

Gastrinoma (Zollinger–Ellison) syndrome.

Less common is ulcer disease associated with massive hypersecretion of acid which occurs rare ______________

H.pylori

This organism is a Gram-negative microaerophilic bacterium found primarily in the gastric antrum of the human stomach. Ninety-five percent or more of duodenal ulcers and 80–85% of gastric ulcers are associated with this.

(a) direct mucosal damage

(b) alterations in host inflammatory responses

(c) hypergastrinemia and elevated acid secretion

H. pylori may cause gastroduodenal mucosal injury through (3)

CagA (cytotoxin associated gene A) and vac A (vacuolating cytotoxin),

The underlying pathophysiology associated with H. pylori infection involves the production of (2)

CagA status and one genotype of the vac A gene

predictors of the ulcerogenic capacity of a strain.

urease, hemolysins, neuraminidase, and fucosidase

a number of enzymes produced by H. pylori may be involved in causing tissue damage and include (4).

Gastrin

is the main hormone involved in stimulating gastric acid secretion, its homeostasis is also altered in H. pylori infection.

H. pylori-induced hypergastrinemia

The hyperacidity in duodenal ulcers may result from

somatostatin

The elevation of gastrin may be a consequence of the bacterially mediated decrease of antral D cells that secrete __________

parietal cell mass

Long-standing hypergastrinemia leads to an increased

metaplastic gastric-type mucosa

The high acid content in the proximal duodenum leads to ________________, which provides a niche for H. pylori infection followed by inflammation and ulcer formation.

superficial erosions

hemorrhages

silent ulcers and ulcers

Three patterns of mucosal damage caused by NSAIDs.

weak

_______NSAIDs, such as acetylsalicylic acid, are concentrated from the acidic gastric juice into mucosal cells and may produce acute superficial erosions via inhibition of COX and by mediating the adherence of leucocytes to mucosal endothelial cells.

prostaglandin production

The major systemic action of NSAIDs that contributes to the formation of ulcers is the reduction of mucosal _________. All NSAIDs share the ability to inhibit COX.

(1) direct irritation of the gastric epithelium, and (2) systemic inhibition of endogenous mucosal PG synthesis.

NSAIDs can cause gastric mucosal damage by two mechanisms:

• Age greater than 65 years

• Previous peptic ulceration/bleeding

• High hose of NSAID or more than 1 NSAID (including aspirin)

• Short-term history of NSAID use (less than 1 month)

• Concomitant corticosteroid or anticoagulant use

• Cardiovascular disease

Risk factors for NSAID ulcers include

selective COX-2 inhibitors

_________tend not to reduce the mucosal production of protective prostaglandins to the same extent as NSAIDs.

COX-2 inhibitors

considered to be safer than non-selective NSAIDs in patients at high risk of developing gastrointestinal mucosal damage.

NO-releasing NSAIDs

NSAIDs that are being investigated to see if the gastric mucosa protection associated with nitric oxide prevents ulceration when prostaglandins are inhibited by NSAIDs.

Abdominal pain

is the most frequent PUD symptom. Pain is often epigastric and described as burning but can present as vague discomfort, abdominal fullness, or cramping.

Nocturnal pain

may awaken patients from sleep, especially between 12 am and 3 am.

duodenal

Pain from ______ulcers often occurs 1 to 3 hours after meals and is usually relieved by food,

gastric

food may precipitate or accentuate ulcer pain in ____ ulcers

gastric ulcers

Heartburn, belching, and bloating often accompany pain. Nausea, vomiting, and anorexia are more common in ____ ulcers

bleeding

_______ is the most frequent and severe complication of peptic ulcer disease.

endoscopy

is generally the investigation of choice for diagnosing peptic ulcers, and the procedure is sensitive, specific, and safe. However, it is also invasive and expensive.

Double-contrast barium

radiography that should detect 80% of peptic ulcers. However, endoscopy is more accurate and almost always preferred.

Gastrograffin®

A _________meal is used to diagnose peptic perforation in patients presenting with an acute abdomen if a plain abdominal X-ray is not diagnostic.

serologic test to detect antibodies

urea breath tests

stool antigen tests

H.pylori detection (non invasive)

Urea breath tests

have a sensitivity and specificity of over 90% and are accurate for both initial diagnosis and confirmation of eradication. The test is based on the principle that urease activity in the stomach of infected individuals hydrolyses urea to form ammonia and carbon dioxide.

stool antigen test

uses an enzyme immunoassay to detect H. pylori antigen in stool. This test also has a sensitivity and specificity of over 90% and can be used in the initial diagnosis and also to confirm eradication.

Serological tests

are based on the detection of anti-H. pylori IgG antibodies but are not able to distinguish between exposure to infection

urease tests, histology, and culture.

Invasive tests for detecting H.pylori requiring gastric antral biopsies include (3)

biopsu urease test

among the invasive test for detecting H.pylori which is the most widely used

spicy foods, caffeine, alcohol

patients should avoid foods and beverages that cause dyspepsia or exacerbate ulcer symptoms examples

Elective surgery

a non-pharmacological treatment that is is rarely performed because of highly effective medical management. Emergency surgery may be required for bleeding, perforation, or obstruction.

proton pump inhibitor (PPI)–based, three-drug regimen for 10 to 14 days.

First-line therapy to eradicate HP infection is usually initiated with a

bismuth salt, metronidazole, tetracycline, and a PPI

If a second treatment course is required in the eradication of H.pylori, the regimen should contain different antibiotics, or a four-drug regimen with a (4) should be used.

Bismuth based quadruple therapy

drug regimen that is recommended as an alternative for patients allergic to penicillin. All medications except the PPI should be taken with meals and at bedtime.

Sequential therapy

the antibiotics are administered in a sequence rather than all together. The rationale is to treat initially with antibiotics that rarely promote resistance (eg, amoxicillin) to reduce bacterial load and preexisting resistant organisms and then to follow with different antibiotics (eg, clarithromycin and remaining organisms. metronidazole) to kill the

A 14-day course of the PPI-based quadruple regimen i

is the most commonly used second-line therapy after failure of a PPI–amoxicillin–clarithromycin regimen.

PPI-based three drug regimen

If a patient was HP positive, start treatment with a

discontinue the NSAID and treat with either a PPI, H2RA, or sucralfate.

if a patient is If HP negative, you should

PPI, PPI based three-drug regimen

If the NSAID must be continued despite ulceration, initiate treatment with a____ (if HP negative) or a ________ (if HP positive).

cyclooxygenase-2 (COX-2) inhibitor

Cotherapy with a PPI or misoprostol or switching to a selective __________is recommended for patients at risk of developing an ulcer-related complication.

PPIs

relieve symptoms and heal peptic ulcers faster than H2-receptor antagonists. They also heal ulcers that are refractory to H2-receptor antagonists.

recommended dose

All PPIs provide similar H. pylori eradication rates and ulcer healing when used at their _________

H+, K+, ATPase, the enzyme

The PPIs are all benzimidazole derivatives that control gastric acid secretion by inhibition of gastric (4) responsible for the final step in gastric acid secretion from the parietal cell.

enteric coating

PPIs require an ________ to protect them from degradation in the acidic environment of the stomach. This delays absorption and a maximum plasma concentration is reached after 2–3 h.

30 min before

All PPIs are most effective if taken about _______ a meal as they inhibit only actively secreting proton pumps. Meals are the main stimulus to proton pump activity.

30–60 min before the first meal of the day.

optimal dosing time of PPI

Omeprazole

Lansoprazole

Pantoprazole

Rabeprazole

Esomeprazole

examples of PPIs (5)

H2-receptor antagonistsm

are less effective than PPIs in eradication regimens, in treating ulcers when NSAIDs are continued, and in prophylaxis of NSAID-induced ulcers.

empirical management of dyspepsia symptoms, if patient with mild symptoms gain adequate relief.

main role of H2-receptor antaganists

heartburn

H2-receptor antagonists are preferred over PPIs in the second-line treatment of ________ in pregnancy,

Bismuth chelate

is a relatively safe form of bismuth that has ulcer-healing properties comparable to those of H2-antagonists.

Bismuth

one of the first agents to be used to eradicate the organism and reduce ulcer recurrence.

Tripotassium dicitratobismuthate in combination with tetracycline, metronidazole and a PPI

bismuth based, used in quadruple therapy regimens in patients resistant to triple therapy.

Sucralfate

is the aluminum salt of sucrose. It has mucosal protective effects including stimulation of bicarbonate and mucus secretion and stimulation of mucosal prostanoids.

4.0

Sucralfate at the pH less than ___ it forms a sticky viscid gel that adheres to the ulcer surface and may afford some physical protection.

bile salts

Sucralfate is capable of adsorbing _____

acid-suppressing

Sucralfate has no _______activity.

2 g twice daily

sucralfate is effective in the treatment of NSAID-induced duodenal ulcers, if the NSAID is stopped in what dose?.

it is not effective in the treatment and prevention of NSAID-related gastric ulcers. It has also been used in the prophylaxis of stress ulceration.

aluminium based and magnesium-based

The choice of antacid lies between _____ and ______ products, although many proprietary products combine both.

acid secretion

Calcium-based products are unsuitable for PUD as calcium stimulates what?

high sodium load and generate large quantities of carbon dioxide.

Antacids containing sodium bicarbonate are unsuitable for regular use because they deliver and generate what?