Peptic Ulcer Disease [P]

Peptic ulcer

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

Peptic ulcer disease (PUD)

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

1. H. pylori

2. NSAID

2 causes of PUD

dyspepsia

Peptic ulcer disease often presents to clinicians as ______________

dyspepsia

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

• non-ulcer or functional dyspepsia

• GORD

• peptic ulcer

The most common causes of dyspepsia are? [3]

Gastrinoma (Zollinger-Ellison) syndrome

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

Helicobacter pylori

This organism is a GRAM-NEGATIVE microaerophilic bacterium found primarily in the gastric antrum of the human stomach

Cytotoxin-associated gene A (Cag A)

Vacuolating cytotoxins (Vac A)

The underlying pathophysiology associated with H. pylori infection involves the production of ___[2]

Gastrin

is the main hormone involved in stimulating gastric acid secretion

Gastrin

This hormone is also altered in H. pylori infection

Somatostatin

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

Hypergastrinemia

___leads to an increased parietal cell mass

► Superficial erosions and hemorrhages,

► Silent ulcers detected at endoscopy,

► ulcers causing clinical symptoms and complications

3 patterns of mucosal damage are caused by NSAIDS. These include:

reduction of mucosal prostaglandin production

The major systemic action of NSAIDs that contributed to the formation of ulcers is the ______________________ ?

Nabumetone

All NSAIDS are weak acids except? (Non acidic NSAID)

- Age greater than 65 yrs

- Previous peptic ulceration/bleeding

- High hose of NSAID or more than 1 NSAID

- Short term history of NSAID use

- Concomitant corticosteroid or anticoagulant use

- Cardiovascular disease

Risk factors for NSAID ulcers include: [6]

Selective COX-2 inhibitors

This TYPE OF DRUG tend not to reduce the mucosal production of protective prostaglandins to the same extent as NSAIDs

COX-2 inhibitors

This TYPE OF DRUG considered to be safer than non-selective NSAIDS in patients at high risk of developing gastrointestinal mucosal damage

Nitric oxide (NO)-releasing NSAIDs

This DRUG 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

1 to 3 hrs

Pain from duodenal ulcers often occurs ___ to ____ hrs after meals and is relieved by food

Antacids

This TYPE OF DRUG provide rapid pain relief in most ulcer patients

• Nausea

• Vomiting

• anorexia

____ [3] are more common in gastric than duodenal ulcers

Peptic ulcer bleeding

This 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

Endoscopy

_____ is invasive and expensive

Double-contrast barium radiography

______ should detect 80% of peptic ulcer

Endoscopy

who is more accurate and almost always preferred (endoscopy or radiology) ?

Gastrograffin meal

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

• Serological tests,

• Urea breath tests,

• Stool antigen tests

Non invasive tests for H. pylori detection [3]

Urea breath tests and Stool antigen test

____ [2] test have a sensitivity and specificity of over 90% and are accurate for both INITIAL DIAGNOSIS and CONFIRMATION of eradication

ammonia and carbon dioxide

The urea breath test is based on the principle that urease activity in the stomach of infected individuals hydrolyses urea to form ____________ and _____________?

Stool antigen test

This test uses an enzyme immunoassay to detect H. pylori

Serological test

This test are based on the detection of anti H.pylori IgG antibodies

Serological test

This test that are not able to distinguish between active or previous exposure to infection

• urease tests

• histology

• culture

Invasive tests requiring gastric antral biopsies include __________, __________, ___________

biopsy urease test

a test that is widely used

• acetaminophen

• nonacetylated salicylate (eg. salsalate)

Alternative agents should be used for pain relief [2]

• spicy foods

• caffeine

• alcohol

Peptic Ulcer patients should avoid this types of foods and beverages like____[3]

PPI inhibitor 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

• PPI

if a second treatment course is required, the regimen should contain ___[4]

Bismuth-based quadruple therapy
► PPI or H2RA
► Bismuth subsalicylate
► Metronidazole
► Tetracyline

is recommended as an alternative for patients allergic to penicillin

PPI

All medications except the ____ should be taken with meals and at bedtime

Sequential therapy
► PPI

► Amoxicillin

► Metronidazole
►Clarithromycin

The antibiotic are administered in a sequence rather than all together

Sequential therapy
► PPI

► Amoxicillin

► Metronidazole
►Clarithromycin

The rationale is to treat initially with antibiotics that rarely promote resistance to bacterial load and preexisting resistant organisms and then to follow with different antibiotics to kill remaining organisms

Second-line (salvage) treatment
►PPI or H2RA

►Bismuth subsalicylate

►Metronidazole

►Tetracyclin

►Amoxicillin

►Levofloxacin

If initial therapy fails to eradicate HP use___ ?

1. Use antibiotics that were not included in the initial regimen

2. Use antibiotics that are not associated with resitance

3. Use a drug that has a topical effect

4. Extend treatment duration to 14 days

If initial treatmen fails to eradicate HP, second-line (salvage) treatment should:

PPI-based three-drug regimen
►PPI
►Clarithromycin

►Amoxicillin/Metronidazole

If HP positive, start treatment with a ___ ?

• NSAID

• PPI, H2RA, or sucralfate
  

If HP negative: discontinue ____ and treat with either a ______[3]

PPI

This TYPE OF DRUG relieve SYMPTOMS and HEAL peptic ulcers faster then H2-receptor antagonists

PPI

___are all benzimadazole derivatives that control gastric acid secretion by inhibition of gastric H+, K+- ATPase,

H+/K+ ATPase

___the enzyme responsible for the final step in gastric acid secetion from the parietal cell

enteric coating

PPIs requre an ________________ to protect them from degradation in the acidic environment of the stomach

30min before a meal

All PPIs are most effective if taken about _________________ as they inhibit only actively secreting proton pumps

Meals

___are the main stimulus to proton pump activity

30-60 min

The optimal dosing time of PPI is _____ min before the first meal of the day

H2-receptor antagonists [H2RA]

___heal ulcers in patients who discontinue their NSAID
______they also have a role in continuing ACID SUPPRESSION for symptomatic treatment following eradication therapy

H2 receptor antagonists

This TYPE OF DRUG main role is in the empirical management of dyspepsia symptoms

H2 receptor antagonists

___are preferred over PPIs in the second-line treatment of heartburn in pregnancy

Bismuth

___has been included in antacid mixtures for many decades but fell from favor because of its neurotoxicity

Bismuth chelate

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

Bismuth chelate

Its mode of action is not clearly understood but it is thought to have cytoprotective properties

Bismuth

___is toxic to H. pylori
___was one of the first agents to be used to eraticate the organism and reduce ulcer recurrence

Tripotrassium dicitratobismuthate in combination with tetracycline metronidazole and a PPI

is used in quadruple therapy regimens in patients resistant to triple therapy

Sucralfate

___is the aluminum salt of sucros octasulphate

Sucralfate

weak antacid, this is not its principal mode of action in peptic ulcer disease

Sucralfate

It has mucosal protective effects including stimulation of bicarbonate and mucosal prostanoids and mucus secretion

4.0

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

Sucralfate

This drug has no acid-suppressing activity

Suralfate

This drug is is effective in the treatment of NSAID-induced duodenal ulcers, if the NSAID is stopped

Sucralfate

___ has also been used in the prophylaxis of stress ulceration

Antacids

___have a place in symptomatic relief of dyspepsia, particular symptoms associated with GERD

aluminum basd and magnesium based

The choice of antacid lies between ______________ and ______________ products, although many propietary products combine both

acid secretion

Calcium-based products are unsuitable as calcium stimulates ____ secretion?

sodium bicarbonate

Antacids containing _______________ are unsuitable for regular use because they deliver a high sodium load and generate large quantities of carbon dioxide