Peptic Ulcers Flashcards
Ulcer Outline
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
Ulcer Causes
NSAIDs, Heliobacter pylori, genetics and lifestyle factors (stress, spicy food, smoking)
Most common presentation of duodenal ulcers
Ages 30-50. Likelihood = Men > women
Most common presentation of gastric ulcers
Age 60+. Likelihood women > men
Mild Ulcer Symptoms
Varying stomach pain (burning/gnawing ) between meals/at night for mins-hrs, fulness without eating, fat intolerance, heartburn and nausea
Serious Ulcer Symptoms
Blood in stool, vomiting blood, shortness of breath and unexplained weight loss
Progression of Ulcer Symptoms if Untreated
Internal bleeding (slow-anemia, fast - need for transfusion), stomach wall perforations (stomach infection), GIT obstruction (food can’t reach stomach) and gastric cancer
Mediators of Gastric acid secretion
Histamine (paracrine hormone, enterochromatin like cells), Acetylcholine (NT, mucosal nerves) and gastrin (endocrine hormone, G cell into portal blood) stimulate parietal cells.
Inhibitors of Gastric Acid Secretion
Somatostatin (hormone, D cells) and prostaglandins E2 and I2
How Somatostatin acts as an inhibitor
increased stomatoststin = decreased gastrin = decreased histamine. Decreased gastrin + decreased histamine = significantly decreased HCl
Prostaglandins Outline
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)
PGE2 and PGI2 Function
Inhibition of parietal cell secretions, stimulant of bicarbonate and mucus secretion, increase mucosal blood flow and epithelial restitution (repair)
During normal physiological function is mucosal defence or aggressive factors (digestion components) favoured
Mucosal defence
What would increase the effect of aggressive factors in stomach
NSAIDs and H pylori
NSAIDs Outline
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
COX 1 Function
Synthesises PGs that regulate acid and mucus secretion in stomach. Constantly (constituently) expressed
COX 2 Function
Synthesises PGs for inflammation and pain response. Induced response
Helicobacter pylori
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
Urease Function
Urea broken down to ammonium and bicarbonate. Ammonium and bicarbonate neutralises stomach acid forming pH gradient in stomach (more neutral near stomach tissue)
H. Pylori Toxins
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
Cag A Effects
Disrupts cell integrity and tight junctions. Increase cytokine secretion and influx of neutrophils
Vac A Effects
Epithelial Apoptosis
H pylori Detection
C13-urea breath test, stool antigen test, serology and endoscopy
Triple Therapy Outline
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
Triple Therapy antibiotics
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
Triple Therapy Acid Suppressing Drugs
PPIs
Differences between triple and quadruple therapies
triple = 1st line and quadruple = 2nd (make sure to not use antibiotics in triple for quadruple). Quadruple therapy uses bismuth
Failure to treat H Pylori Causes
antibiotic resistance and poor patient compliance (due to adverse effects)
Medications for Upper GI disorders
antiacids, alginate gels, H2 receptor antagonists, PPIs and cytoprotective agents
Antacids Outline
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
Side effects of Mg antacids
Diahorrea and toxicity in people with damaged kidneys,
Side effects of Al antacids
Constipation and toxicity in people with damaged kidneys
Side effects of Ca antacids
Hypercalcemia, renal damage and kidney stones
Side effects of Na antacids
Increased risk of hypertension
Alginate Gels Outline
Anionic polysaccharide. Forms a high viscosity gel when interacting with acid in stomach. Neutralises stomach contents that enter esophagus.
H2 antagonists outline
Competitively binds to H2 receptors prevening binding of histamine to parietal cells reducing HCl production.
H2 antagonists side effects
Diahorrea, diziness and muscle pain. Cytocheome P450 inhibition. Relatively safe
PPIs Outline
Inhibit K+-H+ ATPase pumps. Weak bases absorbed by small intestine. Gets activated (prodrug -> drug) in the canaliculi of parietal cells by acidic conditions.
PPIs Side Effects
Rash, nausea, dizziness. Decreases in acidic drug absorption in stomach. Interactions with cytochrome P450 systems
Cytoprotective Agents Outline
Stimulates gastric mucus production and mucosal blood flow. Can also coat ulcerated tissue
Examples of H2 Receptor anatgonists
Cimetidine, Ranitidine and Famotidine
Examples of PPIs
Omeprazole, esomeprazole and lansoprazole
Examples of cytoprotective agents
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)
