Peptic Ulcers

Question 1

Ulcer Outline

Answer 1

Open sores develop on stomach lining and upper portion of intestines. Occurs due to tissue contact with acid (mucosal damage). 2 types: gastric and duodenal

Question 2

Ulcer Causes

Answer 2

NSAIDs, Heliobacter pylori, genetics and lifestyle factors (stress, spicy food, smoking)

Question 3

Most common presentation of duodenal ulcers

Answer 3

Ages 30-50. Likelihood = Men > women

Question 4

Most common presentation of gastric ulcers

Answer 4

Age 60+. Likelihood women > men

Question 5

Mild Ulcer Symptoms

Answer 5

Varying stomach pain (burning/gnawing ) between meals/at night for mins-hrs, fulness without eating, fat intolerance, heartburn and nausea

Question 6

Serious Ulcer Symptoms

Answer 6

Blood in stool, vomiting blood, shortness of breath and unexplained weight loss

Question 7

Progression of Ulcer Symptoms if Untreated

Answer 7

Internal bleeding (slow-anemia, fast - need for transfusion), stomach wall perforations (stomach infection), GIT obstruction (food can’t reach stomach) and gastric cancer

Question 8

Mediators of Gastric acid secretion

Answer 8

Histamine (paracrine hormone, enterochromatin like cells), Acetylcholine (NT, mucosal nerves) and gastrin (endocrine hormone, G cell into portal blood) stimulate parietal cells.

Question 9

Inhibitors of Gastric Acid Secretion

Answer 9

Somatostatin (hormone, D cells) and prostaglandins E2 and I2

Question 10

How Somatostatin acts as an inhibitor

Answer 10

increased stomatoststin = decreased gastrin = decreased histamine. Decreased gastrin + decreased histamine = significantly decreased HCl

Question 11

Prostaglandins Outline

Answer 11

Lipid mediators. Regulate inflammatory response in body. Synthesised from arachidonic acid from epithelial, endothelial and immune cells in mucosa. Synthesis is enzyme dependent (eg COX1 and COX2)

Question 12

PGE2 and PGI2 Function

Answer 12

Inhibition of parietal cell secretions, stimulant of bicarbonate and mucus secretion, increase mucosal blood flow and epithelial restitution (repair)

Question 13

During normal physiological function is mucosal defence or aggressive factors (digestion components) favoured

Answer 13

Mucosal defence

Question 14

What would increase the effect of aggressive factors in stomach

Answer 14

NSAIDs and H pylori

Question 15

NSAIDs Outline

Answer 15

Inhibit COX1 and COX2 enzymes = inhibit prostiglandin production = reduces inflammation response. Reduce pain and fever temperature. Eg aspirin. Most target COX2 but they can interact with COX 1 aswell

Question 16

COX 1 Function

Answer 16

Synthesises PGs that regulate acid and mucus secretion in stomach. Constantly (constituently) expressed

Question 17

COX 2 Function

Answer 17

Synthesises PGs for inflammation and pain response. Induced response

Question 18

Helicobacter pylori

Answer 18

Spiral-bacillus, gram negative bacteria. Transmitted fecal-oral (eg contaminated drinking water). Infection may be asymptomatic or dyspepsia symptoms. produces urease. Travels to stomach epithelium through mucus layer and attaches with adhesions

Question 19

Urease Function

Answer 19

Urea broken down to ammonium and bicarbonate. Ammonium and bicarbonate neutralises stomach acid forming pH gradient in stomach (more neutral near stomach tissue)

Question 20

H. Pylori Toxins

Answer 20

Cytotoxin associated gene A (CagA) and Vacuolating Cytotoxic Protein (VacA). Disrupting epithelia and removing bicarbonate umbrella. Allows pepsin and acid to come into contact with mucosa

Question 21

Cag A Effects

Answer 21

Disrupts cell integrity and tight junctions. Increase cytokine secretion and influx of neutrophils

Question 22

Vac A Effects

Answer 22

Epithelial Apoptosis

Question 23

H pylori Detection

Answer 23

C13-urea breath test, stool antigen test, serology and endoscopy

Question 24

Triple Therapy Outline

Answer 24

1st line of treatment. The use of at least 2 antibiotics (prevention of H pylori developing ressistance) and an acid supressing drug (healing of lining). Treated for 14 days and retested for H pylori

Question 25

Triple Therapy antibiotics

Answer 25

Clarithromycin (main), amoxicillin and metronidazole. Antibiotics chosen based on patient's histories: allergies, previous doses (try not to perscribe same one - prevent ressistance development) and

Question 26

Triple Therapy Acid Suppressing Drugs

Answer 26

PPIs

Question 27

Differences between triple and quadruple therapies

Answer 27

triple = 1st line and quadruple = 2nd (make sure to not use antibiotics in triple for quadruple). Quadruple therapy uses bismuth

Question 28

Failure to treat H Pylori Causes

Answer 28

antibiotic resistance and poor patient compliance (due to adverse effects)

Question 29

Medications for Upper GI disorders

Answer 29

antiacids, alginate gels, H2 receptor antagonists, PPIs and cytoprotective agents

Question 30

Antacids Outline

Answer 30

Treat mild and infrequent symptoms. Ca, Mg, Al or Na salts. Neutralises (increases) pH of stomach contents. Quick acting and unsustained release. Can possibly prevent the absorption of acidic drugs in stomach and can chelate with divalent ions

Question 31

Side effects of Mg antacids

Answer 31

Diahorrea and toxicity in people with damaged kidneys,

Question 32

Side effects of Al antacids

Answer 32

Constipation and toxicity in people with damaged kidneys

Question 33

Side effects of Ca antacids

Answer 33

Hypercalcemia, renal damage and kidney stones

Question 34

Side effects of Na antacids

Answer 34

Increased risk of hypertension

Question 35

Alginate Gels Outline

Answer 35

Anionic polysaccharide. Forms a high viscosity gel when interacting with acid in stomach. Neutralises stomach contents that enter esophagus.

Question 36

H2 antagonists outline

Answer 36

Competitively binds to H2 receptors prevening binding of histamine to parietal cells reducing HCl production.

Question 37

H2 antagonists side effects

Answer 37

Diahorrea, diziness and muscle pain. Cytocheome P450 inhibition. Relatively safe

Question 38

PPIs Outline

Answer 38

Inhibit K+-H+ ATPase pumps. Weak bases absorbed by small intestine. Gets activated (prodrug -> drug) in the canaliculi of parietal cells by acidic conditions.

Question 39

PPIs Side Effects

Answer 39

Rash, nausea, dizziness. Decreases in acidic drug absorption in stomach. Interactions with cytochrome P450 systems

Question 40

Cytoprotective Agents Outline

Answer 40

Stimulates gastric mucus production and mucosal blood flow. Can also coat ulcerated tissue

Question 41

Examples of H2 Receptor anatgonists

Answer 41

Cimetidine, Ranitidine and Famotidine

Question 42

Examples of PPIs

Answer 42

Omeprazole, esomeprazole and lansoprazole

Question 43

Examples of cytoprotective agents

Answer 43

misoprostol (oral PGE2 analogue, increased mucus + bicarbonate secretion. Abdominal cramps + uterine contractions), sucralfate (Al hydroxide and sulfated sucrose, forms paste over ulcerated mucosa, not absorbed in GIT) and bismuth (increases mucus secretion (doesn't neutralise pH), toxic for H pylori. Nausea and vomiting)