Peptic Ulcers: Causes and Treatment
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Questions and Answers

What is one recognized cause of peptic ulcers?

  • Consuming dairy products
  • High carbohydrate diet
  • Use of NSAIDs (correct)
  • Excessive water intake

    • Which therapy is considered effective in treating peptic ulcer disease?

  • Surgical intervention only
  • Dietary adjustments alone
  • Triple therapy including antimicrobial agents (correct)
  • Single antibiotic treatment

    • What is the underlying mechanism of action for proton pump inhibitors?

  • Neutralizing stomach acids
  • Inhibiting histamine receptors
  • Blocking acid production in the stomach (correct)
  • Stimulating gastric motility

    • Which agent is used to counteract nausea and vomiting by targeting serotonin receptors?

    <p>Serotonin 5-HT3 antagonists</p> Signup and view all the answers

    Which of the following statements about gastro-oesophageal reflux disease (GERD) is correct?

    <p>It can be associated with lower esophageal sphincter dysfunction.</p> Signup and view all the answers

    What is the primary effect of chronic NSAID use on gastric function?

    <p>Increased gastric acid secretion</p> Signup and view all the answers

    Which of the following drugs is considered a non-steroidal anti-inflammatory drug (NSAID)?

    <p>Aspirin</p> Signup and view all the answers

    How do COX-1 and COX-2 differ in their roles in the body?

    <p>COX-1 is constitutively expressed, COX-2 is inducible</p> Signup and view all the answers

    What is a common complication associated with the chronic use of NSAIDs?

    <p>Peptic ulcers</p> Signup and view all the answers

    What treatment is often recommended alongside the withdrawal of NSAIDs for induced ulcers?

    <p>Proton pump inhibitors (PPIs)</p> Signup and view all the answers

    Which condition should patients with NSAID-induced ulcers be tested for?

    <p>Helicobacter pylori infection</p> Signup and view all the answers

    What is a significant consequence of NSAIDs inhibiting prostaglandin synthesis?

    <p>Reduced blood flow to the mucosa</p> Signup and view all the answers

    What factor should be considered when deciding to withdraw NSAIDs from a patient?

    <p>The risk profile of the NSAID being used</p> Signup and view all the answers

    What is the primary cause of inflammation and epithelial cell death in H pylori infection?

    <p>Acid and pepsin access to the mucosa</p> Signup and view all the answers

    Which of the following is NOT a common acid-suppressing drug used in the treatment of H pylori infection?

    <p>Tetracycline</p> Signup and view all the answers

    What is the recommended duration for the treatment of H pylori infection?

    <p>14 days</p> Signup and view all the answers

    Which antibiotic is preferred for first-line therapy if a patient is allergic to penicillin?

    <p>Metronidazole</p> Signup and view all the answers

    What is the approximate lifetime risk of developing an endoscopic ulcer in H pylori positive individuals?

    <p>10-20%</p> Signup and view all the answers

    Which option is true regarding resistance in H pylori treatment?

    <p>Resistance to metronidazole is common</p> Signup and view all the answers

    Which component of H pylori works to neutralize stomach acid?

    <p>Urease</p> Signup and view all the answers

    When should a repeat breath test be conducted after completing antibiotic treatment for H pylori?

    <p>2 weeks</p> Signup and view all the answers

    What triggers the vomiting center in the brain stem?

    <p>Both chemical and neural activation</p> Signup and view all the answers

    Which anti-emetic drug is a peripheral D2 dopamine antagonist?

    <p>Domperidone</p> Signup and view all the answers

    What is a primary side effect of Metoclopramide?

    <p>Dyskinesia</p> Signup and view all the answers

    Which condition can Metoclopramide be used to treat?

    <p>Chemotherapy-induced nausea and vomiting</p> Signup and view all the answers

    What is the mechanism of action for cannabinoids like nabilone in treating nausea?

    <p>They activate CB1 and CB2 receptors in the medulla oblongata.</p> Signup and view all the answers

    What are common side effects of H1 antagonists like diphenhydramine?

    <p>Drowsiness</p> Signup and view all the answers

    Which statement about Muscarinic antagonists is true?

    <p>They are used for motion sickness.</p> Signup and view all the answers

    What effect does dopamine have on the gastrointestinal tract?

    <p>Has a relaxant effect by activating D2 receptors.</p> Signup and view all the answers

    What is a common reason for non-adherence in patients undergoing H. pylori treatment?

    <p>Adverse effects such as abdominal pain</p> Signup and view all the answers

    What is the mainstay of treatment for gastro-oesophageal reflux disease (GERD)?

    <p>Proton pump inhibitors (PPIs)</p> Signup and view all the answers

    Which of the following is a likely side effect of using proton pump inhibitors?

    <p>Drug interactions with cytochrome P450</p> Signup and view all the answers

    What condition is characterized by chronic reflux of stomach acid into the esophagus?

    <p>Gastro-oesophageal reflux disease (GERD)</p> Signup and view all the answers

    In the treatment of peptic ulcer disease, what is the recommended duration for standard therapy?

    <p>14 days</p> Signup and view all the answers

    What is the primary method by which H2 receptor antagonists reduce gastric acid secretion?

    <p>Competitively inhibit H2 receptors</p> Signup and view all the answers

    Which of the following treatments is used for NSAID-induced ulcers?

    <p>Misoprostol</p> Signup and view all the answers

    What type of agent acts by forming a protective coating over ulcerated tissue?

    <p>Sucralfate</p> Signup and view all the answers

    What is a potential side effect of antacids that contain calcium salts?

    <p>Hypercalcemia</p> Signup and view all the answers

    Which side effect is associated with the use of H2 receptor antagonists?

    <p>Diarrhea</p> Signup and view all the answers

    What is one major aspect that affects the success of H. pylori treatment?

    <p>Patient adherence to the regimen</p> Signup and view all the answers

    Which of the following treatments provides immediate relief of mild acid-related symptoms?

    <p>Antacids</p> Signup and view all the answers

    Which of the following does not have a direct acid-neutralizing capacity?

    <p>Bismuth salts</p> Signup and view all the answers

    What is a significant effect of chronic NSAID use on gastric mucosa?

    <p>Decreased mucosal blood flow</p> Signup and view all the answers

    What role does COX-1 play in the gastrointestinal system?

    <p>Regulates mucus and bicarbonate secretion</p> Signup and view all the answers

    What is one potential consequence of withdrawing NSAIDs in patients with chronic pain?

    <p>Deterioration of the pain management strategy</p> Signup and view all the answers

    Which factor should be closely monitored when prescribing NSAIDs?

    <p>Patient's history of cardiovascular disease</p> Signup and view all the answers

    What is considered an effective approach to promoting healing of NSAID-induced ulcers?

    <p>Commencing proton pump inhibitors</p> Signup and view all the answers

    How do COX-2 inhibitors differ from COX-1 in terms of gastric effects?

    <p>COX-2 inhibitors generally cause fewer gastric ulcers</p> Signup and view all the answers

    Why should patients with NSAID-induced ulcers be tested for H.pylori?

    <p>H.pylori can complicate ulcer healing and increase risks</p> Signup and view all the answers

    What might be a consequence of increased gastric acid secretion due to chronic NSAID use?

    <p>Higher risk of ulcer formation</p> Signup and view all the answers

    At what age range are duodenal ulcers most likely to develop?

    <p>30 to 50 years</p> Signup and view all the answers

    Which symptom is primarily indicative of a serious peptic ulcer condition?

    <p>Dark blood in stools</p> Signup and view all the answers

    What role does histamine play in gastric acid secretion?

    <p>Acts on the parietal cell to increase cAMP levels</p> Signup and view all the answers

    What is the function of prostaglandins like PGE2 and PGI2 in the stomach?

    <p>Enhance mucus and bicarbonate secretion</p> Signup and view all the answers

    How do aggressive factors contribute to peptic ulcers?

    <p>Cause damage through high levels of gastric acid</p> Signup and view all the answers

    Which of the following is NOT an inhibitory factor in gastric acid secretion?

    <p>Gastrin</p> Signup and view all the answers

    What physiological function does increased mucosal blood flow serve in the stomach?

    <p>Promotes epithelial cell renewal</p> Signup and view all the answers

    Which hormone is primarily involved in increasing histamine release from enterochromaffin-like cells (ECLs)?

    <p>Gastrin</p> Signup and view all the answers

    In peptic ulcer pathophysiology, what does the balance between aggressive factors and mucosal defense indicate?

    <p>A healthy regulation of acids and defenses</p> Signup and view all the answers

    What is a common occurrence in gastric ulcers compared to duodenal ulcers regarding gender?

    <p>Women are more affected than men</p> Signup and view all the answers

    What mechanism allows H pylori to survive in the acidic environment of the stomach?

    <p>Expression of urease that neutralizes acid</p> Signup and view all the answers

    What is the preferred first-line treatment regimen for H pylori infection in patients not allergic to penicillin?

    <p>PPI, clarithromycin, amoxicillin</p> Signup and view all the answers

    What consequence is common if H pylori treatment fails?

    <p>Development of antibiotic resistance</p> Signup and view all the answers

    What is the typical risk of reinfection with H pylori within three years after successful eradication?

    <p>10%</p> Signup and view all the answers

    Which antibiotic is less likely to be associated with resistance in H pylori treatment?

    <p>Amoxicillin</p> Signup and view all the answers

    If a patient has a history of treatment with metronidazole for another infection, which first-line combination should be administered for H pylori?

    <p>PPI, clarithromycin, amoxicillin</p> Signup and view all the answers

    What is the most common reason for treatment failure in H pylori eradication therapies?

    <p>Development of resistance to clarithromycin</p> Signup and view all the answers

    If a patient is allergic to penicillin and has a history of treatment with clarithromycin, which therapy is suggested?

    <p>Quadruple therapy with PPI, metronidazole, tetracycline, bismuth</p> Signup and view all the answers

    What is the primary reason contributing to the failure of H. pylori treatment?

    <p>Patient non-adherence</p> Signup and view all the answers

    What is a key consideration when planning therapy for H. pylori eradication?

    <p>Patient's previous exposures to antibiotics</p> Signup and view all the answers

    Which of the following is NOT a component often found in the treatment regimen for H. pylori?

    <p>Non-steroidal anti-inflammatory drugs</p> Signup and view all the answers

    What is the mechanism of action for H2 receptor antagonists in reducing gastric acid secretion?

    <p>Blocking the histamine H2 receptors on parietal cells</p> Signup and view all the answers

    What is a common side effect specifically associated with the use of proton pump inhibitors?

    <p>Headache</p> Signup and view all the answers

    Which type of mediation promotes mucosal blood flow and decreases acid secretion?

    <p>Cytoprotective agents</p> Signup and view all the answers

    What condition can arise from chronic gastro-oesophageal reflux disease (GERD)?

    <p>Barrett's esophagus</p> Signup and view all the answers

    What determines the effectiveness of proton pump inhibitors?

    <p>Patient adherence to dosage schedule</p> Signup and view all the answers

    What is a likely consequence of discontinuing proton pump inhibitor therapy abruptly?

    <p>Rebound acid secretion</p> Signup and view all the answers

    Which substances can directly neutralize stomach acid in a quick manner?

    <p>Antacids</p> Signup and view all the answers

    What side effect is specifically caused by magnesium-containing antacids?

    <p>Diarrhea</p> Signup and view all the answers

    What is the main action of bismuth salts in ulcer treatment?

    <p>Mucosal protection</p> Signup and view all the answers

    What is a prominent drug interaction concern with H2 receptor antagonists like cimetidine?

    <p>Altered metabolism of other drugs</p> Signup and view all the answers

    What type of agents form a viscous solution that can help prevent acid reflux?

    <p>Raft-forming agents</p> Signup and view all the answers

    What role does the chemoreceptor trigger zone (CTZ) play in the vomiting process?

    <p>It mediates chemical activation sensitive to toxins in the bloodstream.</p> Signup and view all the answers

    Which of the following prokinetic agents does not cross the blood-brain barrier?

    <p>Domperidone</p> Signup and view all the answers

    What are the primary side effects associated with the use of high-dose Metoclopramide?

    <p>Drowsiness, fatigue, and dyskinesia</p> Signup and view all the answers

    In which scenario are 5-HT3 antagonists like ondansetron most effectively used?

    <p>Chemotherapy-induced nausea and vomiting</p> Signup and view all the answers

    Which of the following statements about cannabinoid anti-emetics is incorrect?

    <p>They are effective for motion sickness.</p> Signup and view all the answers

    For what specific condition should Metoclopramide not be used due to its side effects?

    <p>Patients with Parkinson's disease</p> Signup and view all the answers

    What mechanism do muscarinic antagonists use to alleviate motion sickness?

    <p>Blocking receptors in the vestibular nucleus and vomiting center.</p> Signup and view all the answers

    What is the primary effect of dopamine on the gastrointestinal tract?

    <p>It causes relaxation of the stomach muscle.</p> Signup and view all the answers

    How do NK1 antagonists function in managing CINV?

    <p>By blocking substance P signaling in the brain.</p> Signup and view all the answers

    What is a common adverse effect of H1 antagonists like diphenhydramine when used for motion sickness?

    <p>Drowsiness</p> Signup and view all the answers

    Study Notes

    Peptic Ulcers

    • Peptic ulcers are open sores that develop on the inner lining of the stomach or upper small intestine.
    • Acid-induced damage to the mucosa.
    • Causes include NSAID use and Helicobacter pylori (H. pylori) infection.
    • Other factors that can contribute to ulcer development include genetics, stress, spicy foods, and smoking.

    Drug-Induced Ulceration

    • Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to relieve pain, reduce inflammation, and lower fever.
    • Examples of NSAIDs include aspirin, ibuprofen, diclofenac, and naproxen.
    • Chronic NSAID use can lead to increased gastric acid secretion, decreased mucus and bicarbonate secretion, decreased mucosal blood flow, and impaired epithelial restitution.
    • This combination of effects can promote ulcer development.

    Treatment of NSAID-Induced Ulcers

    • NSAID-induced ulcers typically heal after discontinuing the NSAID.
    • Additional treatment with a proton pump inhibitor (PPI) may be recommended to promote healing.
    • When deciding to withdraw an NSAID, consider the risk-benefit profile for the patient, taking into account factors such as the:
      • The risk profile of the specific NSAID (e.g., naproxen vs. ibuprofen)
      • The type of COX enzyme targeted (COX-1 vs. COX-2)
      • The dose and duration of NSAID use
      • Concomitant medications (e.g., low-dose aspirin, steroids)
    • Consider starting a PPI like omeprazole.
    • Test for H. pylori infection in patients experiencing NSAID-induced gastrointestinal events and treat if present.
    • Managing chronic pain in patients with peptic ulcers can be a challenge if NSAIDs need to be discontinued.

    H. Pylori and Peptic Ulcer Disease

    • Helicobacter pylori (H. pylori) is a motile, gram-negative, spiral bacillus.
    • Infection is common and usually occurs during childhood.
    • Around 50% of people over 40 have H. pylori in their stomachs. This percentage is even higher in developing countries.
    • The lifetime risk of developing an endoscopic ulcer is 10-20% for H. pylori positive individuals.
    • H. pylori can survive in stomach acid because it expresses urease, which converts urea into ammonia and bicarbonate, neutralizing the acid.
    • H. pylori infects gastric epithelial cells and causes inflammation and cell death, leading to a loss of barrier function and increased exposure of the mucosa to acid and pepsin, contributing to ulceration.

    Treatment of H. Pylori Infection

    • Triple therapy is the most effective treatment for H. pylori infection. It involves the use of two different antibiotics to prevent resistance and an acid-suppressing drug to promote healing.
    • Common antibiotic choices include amoxicillin, clarithromycin, metronidazole, or tetracycline.
    • Proton pump inhibitors (PPIs) like omeprazole, pantoprazole, or esomeprazole are commonly used to reduce acid production.
    • Treatment typically lasts 14 days.
    • Repeat breath tests are recommended at least two weeks after completing PPI treatment and four weeks after finishing antibiotic therapy.
    • If breath test results show the infection is gone, chances of re-infection within three years are around 10%.
    • If the infection persists, progress to a second-line therapy regimen.

    HSE Recommendations for H. Pylori Treatment

    • First-line therapy: Clarithromycin triple therapy is commonly used:
      • PPI
      • Clarithromycin
      • Amoxicillin or metronidazole (consider metronidazole for penicillin allergy)
    • Alternative therapies:
      • Penicillin allergy: Use metronidazole and clarithromycin.
      • Previous metronidazole use: Use clarithromycin and amoxicillin.
      • Previous clarithromycin use: Use amoxicillin and metronidazole.
      • Penicillin allergy and previous clarithromycin use: Consider quadruple therapy — PPI, metronidazole, tetracycline, and bismuth.

    Treatment Failure

    • Treatment failure for H. pylori infection is usually due to:
      • Antibiotic resistance: This is more common with clarithromycin and metronidazole and can develop during treatment. Resistance to amoxicillin is rare.
      • Poor adherence: This can occur in up to 20% of patients, often due to adverse effects such as abdominal pain, diarrhea, altered taste, headache, or vomiting.

    Second-Line Therapy

    • If first-line therapy fails, initiate a second-line therapy regimen.
    • Second-line regimens should use different antibiotics than those used in the first-line regimen.

    Gastro-Oesophageal Reflux Disease (GORD/GERD)

    • Heartburn: This is a common symptom of acid reflux, occurring when the lower oesophageal sphincter (LOS) doesn't close completely, allowing stomach acid to reflux into the oesophagus.
    • Symptoms: Burning, coughing, and hoarseness.
    • Chronic reflux: When reflux is chronic and frequent, it is known as gastro-oesophageal reflux disease (GORD/GERD).
    • Complications: GORD can cause oesophageal inflammation (oesophagitis), ulcers, and ultimately, Barrett's oesophagus – a precancerous condition.
    • Diagnosis: Upper GI endoscopy.
    • Treatment:
      • Lifestyle changes: Diet modifications, changes in eating habits, and weight management.
      • Oral medications: Antacids, histamine H2 antagonists, and PPIs like esomeprazole.

    Proton Pump Inhibitors (PPIs)

    • PPIs are the most potent class of acid-suppressing drugs. They act as the mainstay treatment for acid suppression in conditions such as peptic ulcer disease, GORD, and for the prophylaxis of ulcer development (e.g., in patients taking NSAIDs).
    • PPIs irreversibly inhibit the H+-K+-ATPase, the enzyme responsible for pumping protons into the stomach lumen to acidify the stomach.
    • Mechanism of action:
      • PPIs are weak bases and are readily absorbed in the small intestine.
      • They accumulate in the canaliculi of parietal cells, concentrating up to 1000 times higher than in the blood.
      • Activation occurs in the acidic environment of the stomach, triggering the conversion of the PPI prodrug into a sulfenamide compound, which covalently binds to the proton pump, inhibiting its activity.
    • Examples of PPIs include omeprazole, esomeprazole, and lansoprazole.

    Administration and Pharmacokinetics of PPIs

    • Oral administration: Take 30 minutes before food.
    • Bioavailability: High, ranging from 80% to 90%.
    • Half-life: Short, typically 1-2 hours.
    • Duration of action: Long, lasting 48-72 hours due to irreversible inhibition of the proton pump.

    Side effects of PPIs

    • Generally well tolerated.
    • Potential side effects include headache, nausea, dizziness, and rash.
    • Drug interactions:
      • Altered drug absorption: PPIs increase gastric pH, which can affect the absorption of some drugs.
        • Increased absorption of digoxin.
        • Decreased absorption of ketoconazole.
      • Cytochrome P450 system interaction: PPIs can alter the metabolism of other drugs.

    Histamine H2 Receptor Antagonists

    • Histamine is released from enterochromaffin-like (ECL) cells in the stomach.
    • It acts locally on H2 receptors on parietal cells.
    • Histamine binding to H2 receptors increases cyclic adenosine monophosphate (cAMP) levels, activating protein kinase A (PKA) and ultimately leading to increased acid secretion.
    • Histamine H2 receptor antagonists competitively inhibit H2 receptors, reducing both histamine-stimulated and basal acid secretion.
    • Mechanism of action: They reduce gastric acid secretion by up to 90%.
    • Examples include cimetidine, ranitidine, and famotidine.

    Administration and Pharmacokinetics of H2 Receptor Antagonists

    • Oral absorption: Rapid from the small intestine.
    • Peak concentrations: Achieved 1-3 hours after administration.
    • Elimination: Primarily through glomerular filtration and tubular secretion.

    Side Effects of H2 Receptor Antagonists

    • Generally very safe.
    • Potential side effects include diarrhea, dizziness, and muscle pain.
    • Drug interactions:
      • Cytochrome P450 inhibition: Cimetidine can inhibit CYP450 enzymes, leading to altered metabolism of other drugs (e.g., phenytoin, theophylline, warfarin).
      • Altered drug absorption: H2 receptor antagonists increase stomach pH, reducing the absorption of drugs that require an acidic environment for absorption (e.g., ketoconazole, aspirin).
    • Rare adverse effects: Nephrotoxicity and hepatotoxicity.
    • Contraindications: Contraindicated in patients with hepatic failure or renal insufficiency due to potential for toxicity.

    Cytoprotective Agents

    • Misoprostol:
      • A stable analogue of prostaglandin E2.
      • Administered orally.
      • Mechanisms of action:
        • Decreases acid secretion from parietal cells.
        • Increases mucus and bicarbonate secretion.
        • Inhibits histamine release from ECL cells.
      • Efficacy: Particularly useful in treating NSAID-induced ulcers because it bypasses COX-2 inhibition to act directly at PG receptors.
      • Side effects: Diarrhea, abdominal cramps, uterine contractions.
    • Sucralfate:
      • A complex of aluminium hydroxide and sulfated sucrose.
      • Given orally.
      • Activation: Activated in the acidic environment of the stomach, forming a paste.
      • Mechanism of action:
        • Binds to proteins in the ulcerated mucosa, forming a viscous cytoprotective gel.
        • Protects the ulcerated mucosa from acid, pepsin, and bile salts.
        • Induces an increase in mucosal prostaglandins.
        • Maintains mucosal blood flow.
        • Increases bicarbonate and mucus secretion.
      • Side Effects: Generally well tolerated as it is not absorbed from the GI tract. Potential side effects include constipation, nausea, and hypophosphatemia.
      • Drug interactions: Can affect the bioavailability of some drugs (e.g., tetracyclines, digoxin).

    Bismuth Salts

    • Administration: Given orally in a salt form, such as bismuth subsalicylate.
    • Mechanism of action:
      • Not a significant acid-neutralizing agent.
      • Binds to and protects mucosal lesions.
      • Inhibits the proteolytic action of pepsin.
      • Increases mucus secretion.
      • Toxic to Helicobacter pylori (used in quadruple therapy).
    • Side Effects: Nausea and vomiting. Causes reversible blackening of the tongue and faeces.

    Antacids

    • Use: Relieving mild and infrequent symptoms associated with acid-related disease.
    • Ingredients: Calcium, magnesium, aluminium, or sodium salts.
    • Mechanism of action: Direct neutralization of acid, leading to an increase in gastric pH.
    • Speed of action: Rapid, within minutes.
    • Duration of action: Short, typically 30 minutes on an empty stomach and 3 hours when given with or within 1 hour of a meal.
    • Additional Effects:
      • Increased pH can also inhibit the activity of peptic enzymes.
    • Limitations: Should not be used for more than 14 days without consulting a doctor.
    • Tolerability: Generally well tolerated.

    Side effects of Antacids

    • Magnesium salts: Can cause diarrhoea.
    • Aluminium salts: Can cause constipation.
      • Combining magnesium and aluminium salts can help maintain normal bowel function.
    • Systemic absorption: Aluminium and magnesium can be absorbed systemically but typically do not cause problems. However, toxicity can arise in patients with renal insufficiency.
    • Calcium salts (e.g., calcium carbonate):
      • Can cause hypercalcaemia, kidney stones, and milk-alkali syndrome.
    • Phosphate binding: All antacids can bind phosphate in the gut, leading to hypophosphatemia and potential for bone demineralisation (rickets).
    • Sodium salts (e.g., sodium bicarbonate):
      • Causes sodium retention, which can be problematic in patients with hypertension.
      • Can induce systemic alkalosis, leading to nausea, muscle spasms, tremors, confusion, and difficulty breathing.

    Drug Interactions of Antacids

    • Decreased absorption of acidic drugs: Antacids decrease the absorption of some acidic drugs (e.g., digoxin and ketoconazole).
    • Chelation with divalent ions: Antacids can chelate divalent ions, hindering the absorption of certain drugs (e.g., tetracyclines and fluoroquinolones).
    • Altered dissolution of enteric coatings: Antacids can affect the dissolution of pH-sensitive enteric coatings.
    • Urinary alkalisation: Antacids can cause urinary alkalisation, altering the elimination of many drugs (e.g., salicylates).
    • Important note: Separate antacid administration from interacting drugs by at least two hours to minimize potential interactions!

    Raft-Forming agents

    • These are not acid-neutralizing agents.
    • They form viscous solutions that float on top of gastric contents, preventing acid reflux.
    • Examples include guar gum, xanthan gum, carrageenan, pectin, locust bean gum, and alginates (alginic acid).

    Nausea and Vomiting

    • Nausea: Feeling of stomach distress, with distaste for food and urge to vomit.
    • Vomiting: Disgorging stomach (and sometimes small intestinal) contents through the mouth.
    • Physiological function: Vomiting serves as a natural defense mechanism to prevent poisoning and infection.
    • Symptom: Vomiting can be a symptom of a underlying illness.

    Control of Vomiting

    • CNS control: Vomiting is a reflex controlled by the central nervous system (CNS).
    • Medulla oblongata: Structures involved in vomiting control are found in the medulla oblongata, the most primitive area of the brain responsible for regulating essential involuntary functions and basic instincts.

    Vomiting Centre

    • Located in the brainstem
    • Activated by:
      • Chemical activation via the chemoreceptor trigger zone (CTZ)
        • Sensitive to toxins and poisons in the bloodstream
      • Neural activation:
        • Information from the frontal lobes, digestive tract, and inner ear
    • Causes hypo-motility and reverse-motility of the digestive tract
    • This forces stomach contents up through the esophagus

    Anti-Emetics

    • Act by restoring normal gastrointestinal motility (prokinetic agents) or by preventing signaling through the vomiting center

    Prokinetic Agents

    • Dopamine antagonists act directly on D2 receptors in the gut, which relax the lower esophageal sphincter and stomach
    • Domperidone
      • Peripheral D2 dopamine antagonist, does not cross the blood-brain barrier
      • Enhances stomach contractions, stimulates gastric emptying, increases lower esophageal sphincter tone
      • Side effects: headache, dry mouth, abdominal cramps, diarrhea
    • Metoclopramide
      • D2 dopamine antagonist and 5-HT4 receptor agonist, crosses the blood-brain barrier
      • Stimulates gastric emptying, enhances stomach contractions, increases lower esophageal sphincter tone
      • Used for chemotherapy-induced nausea and vomiting (CINV) and morning sickness
      • Side effects: fatigue, diarrhea, depression, dyskinesia, contraindicated in patients with Parkinson's disease

    Other Anti-Emetic Drugs

    • 5-HT3 antagonists (e.g., ondansetron)
      • Act in the CTZ, used for CINV and gastroenteritis
      • Can be given orally or intravenously
      • Side effects: constipation, headache, flushing, drowsiness
    • Cannabinoids (e.g., nabilone)
      • Synthetic form of delta-9-tetrahydrocannabinol, acts on CB1 and CB2 receptors in the medulla oblongata
      • Used for CINV, oral administration 1-3 hours before chemotherapy
      • Side effects: vertigo, drowsiness, dry mouth, euphoria
    • Muscarinic antagonists (e.g., hyoscine, scopolamine)
      • Act in the vestibular nucleus and vomit center, used for motion sickness
      • Available as tablets (30 mins before travel) or transdermal patches (5-6 hours before travel)
      • Side effects: blurred vision, dry mouth, tachycardia, constipation, drowsiness
    • H1 antagonists (e.g., diphenhydramine, cyclizine)
      • Act in the vestibular nucleus, used for motion sickness
      • Available as tablets (30-60 minutes before travel)
      • Side effects: drowsiness
    • Corticosteroids (e.g., dexamethasone)
      • Used for CINV
    • NK1 antagonists (e.g., aprepitant)
      • Used for CINV

    Peptic Ulcers

    • 1 in 10 individuals develop a peptic ulcer at some point in their lives.
    • Duodenal ulcers commonly occur between ages 30 and 50, with men being more affected than women.
    • Gastric ulcers occur later in life, typically after age 60, and women experience them more frequently than men.

    Symptoms

    • Mild:
      • Pain is the most common symptom, occurring in the abdomen.
      • Pain can vary in severity, being described as burning or gnawing.
      • Pain is particularly noticeable between meals or at night.
      • Pain episodes can last for minutes to hours.
      • Pain tends to ease with eating or antacid use.
      • Other symptoms include feelings of fullness, bloating, belching, intolerance to fatty foods, heartburn, and nausea.
    • Serious:
      • Dark blood in stools.
      • Vomiting or vomiting blood.
      • Trouble breathing.
      • Feeling faint.
      • Unexplained weight loss.

    Gastric Acid Secretion

    • The parietal cell is responsible for producing gastric acid.
    • The parietal cell has canaliculi which are invaginations of the cell membrane that increase the surface area for acid secretion.

    Regulation of Gastric Acid Secretion

    • Stimulatory Factors:
      • Gastrin: Released from G cells into portal blood, acting on CCK2R in parietal cells to increase calcium levels.
      • Acetylcholine: Released by mucosal nerves, acting on M3 receptors on parietal cells to increase calcium levels.
      • Histamine: Released from ECL cells, acting locally on H2 receptors of parietal cells to increase cyclic AMP.
    • Inhibitory Factors:
      • Somatostatin: Released from D cells, inhibiting the release of gastrin, histamine, and ultimately reducing acid production.
      • Prostaglandins (PGE2/PGI2):
        • Inhibit acid secretion from parietal cells.
        • Stimulate mucus and bicarbonate secretion from surface cells.
        • Increase mucosal blood flow.
        • Increase epithelial repair (restitution).

    Pathophysiology of Peptic Ulcers

    • There's a balance between gastric acid secretion and gastroduodenal mucosal defense in healthy individuals.
      • Mucosal Defense: Mucosal blood flow, mucus secretion, mucosal bicarbonate secretion, mucosal cell restitution, and epithelial cell renewal.
      • Aggressive Factors: Gastric acid, pepsin, bile salts, Helicobacter pylori, and NSAIDs.
    • An imbalance between these factors can lead to ulceration.

    Drug-Induced Ulceration

    • NSAIDs are a common cause of peptic ulcers.
    • NSAIDs inhibit COX-1 and COX-2 enzymes, which are responsible for prostaglandin synthesis.
      • COX-1: Constitutively expressed, involved in the regulation of acid and mucus secretion in the stomach.
      • COX-2: Inducible, responsible for mediating inflammation and pain.
    • By inhibiting COX enzymes, NSAIDs:
      • Increase gastric acid secretion.
      • Decrease mucus and bicarbonate secretion.
      • Decrease mucosal blood flow.
      • Decrease epithelial restitution.

    Treatment of NSAID-Induced Ulcers

    • Discontinuation of NSAID use usually leads to ulcer healing.
    • PPIs (proton pump inhibitors) can be used to promote healing.
    • If NSAID use must continue, consider:
      • Risk profile of NSAID, including type, dose, and duration.
      • Concomitant medication (e.g., low-dose aspirin, steroids).
    • H. pylori testing is recommended for NSAID-induced ulcers.
    • Treat H. pylori infection if present.

    H. pylori and Peptic Ulcer Disease

    • H. pylori is a common bacteria found in the stomach.
    • Over 50% of individuals over 40 years old have H. pylori infection.
    • H. pylori can survive in stomach acid by producing urease, which neutralizes acid.
    • Infection with H. pylori is a major risk factor for developing peptic ulcers.
    • H. pylori infects gastric epithelial cells, causing inflammation and damage, leading to ulcer formation.

    Treatment of H. pylori Infection

    • Triple Therapy:
      • Two antibiotics (e.g., amoxicillin, clarithromycin, metronidazole, tetracycline).
      • One acid-suppressing drug (e.g., omeprazole, pantoprazole, esomeprazole).
    • Treatment is typically given for 14 days.
    • A breath test is recommended at least two weeks after PPI treatment and four weeks after completing antibiotic treatment to confirm eradication.
    • If the infection persists, second-line therapy is initiated using different antibiotics.

    Treatment of H pylori Infection: HSE Recommendations

    • First-line therapy: Clarithromycin triple therapy is preferred:
      • PPI
      • Clarithromycin
      • Amoxicillin or metronidazole.
    • Alternative therapies:
      • Metronidazole and clarithromycin for penicillin allergy.
      • Clarithromycin and amoxicillin for previous metronidazole treatment.
      • Amoxicillin and metronidazole for previous clarithromycin treatment.
      • Quadruple therapy (PPI, metronidazole, tetracycline, and bismuth) for penicillin allergy and prior clarithromycin treatment.

    Treatment of H pylori Infection: Treatment Failure

    • Treatment failure usually indicates:
      • Antibiotic resistance: Resistance to amoxicillin is rare, while resistance to clarithromycin and metronidazole is more common.
      • Poor adherence: Up to 20% of patients are non-adherent, often due to side effects like abdominal pain, diarrhoea, altered taste, headache, or vomiting.

    Gastroesophageal Reflux Disease (GORD or GERD)

    • GORD occurs when stomach acid frequently refluxes into the esophagus due to an incompletely closed lower esophageal sphincter.
    • Symptoms include heartburn, burning sensation, cough, and hoarseness.
    • GORD leads to inflammation (esophagitis), ulcers, and potentially Barrett’s esophagus.
    • Diagnosis is made through upper GI endoscopy.
    • Treatment involves lifestyle changes, dietary modifications, weight management, and medications like antacids, H2 antagonists, and PPIs.

    Proton Pump Inhibitors (PPIs)

    • Most potent class of acid-suppressing drugs.
    • Used for treating acid-related disorders like peptic ulcer disease, GORD, and ulcer prophylaxis.
    • Irreversibly inhibit the H+-K+-ATPase, the pump responsible for acid secretion.
    • Well-tolerated, but some side effects include headache, nausea, dizziness, and rash.
    • Drug interactions are possible due to altered gastric pH and interactions with cytochrome P450 system.

    H2 Receptor Antagonists

    • Block histamine receptors on parietal cells, reducing histamine-stimulated acid secretion.
    • Examples include cimetidine, ranitidine, and famotidine.
    • Generally safe, but potential side effects include diarrhoea, dizziness, and muscle pain.
    • Drug interactions can occur due to cytochrome P450 inhibition and alterations in gastric pH.

    Cytoprotective Agents

    • Misoprostol:
      • Analogue of prostaglandin E2.
      • Decreases acid secretion, increases mucus and bicarbonate secretion, and inhibits histamine release.
      • Used for NSAID-induced ulcers.
      • Side effects include diarrhoea, abdominal cramps, and uterine contractions.
    • Sucralfate:
      • Forms a protective gel over ulcerated mucosa.
      • Protects from acid, pepsin, and bile salts.
      • Increases mucosal PG concentration.
      • Well-tolerated, but potential side effects include constipation, nausea, and hypophosphatemia.

    Bismuth Salts

    • Oral medication like bismuth subsalicylate.
    • MOA unclear, but known effects include:
      • Binding and protection of mucosal lesions.
      • Inhibition of pepsin proteolytic action.
      • Increased mucus secretion.
      • Toxicity to H. pylori.
    • Used in quadruple therapy for H. pylori infection.
    • Side effects include nausea, vomiting, and reversible blackening of the tongue and faeces.

    Antacids

    • Relieve mild and infrequent symptoms of acid-related disease.
    • Directly neutralize acid, increasing gastric pH.
    • Rapid onset but short duration of action.
    • Can inhibit pepsin activity.
    • Should not be used for more than 14 days without consulting a doctor.
    • Well tolerated but potential side effects depend on the salt used (calcium, magnesium, aluminum, or sodium).

    Antacids: Side Effects

    • Magnesium salts: May cause diarrhoea.
    • Aluminum salts: May cause constipation. Combination products can balance these effects.
    • Calcium salts: Can lead to hypercalcemia, kidney stones, and milk-alkali syndrome.
    • All antacids: Can bind phosphate in the gut, leading to hypophosphatemia and bone demineralization.
    • Sodium bicarbonate: Can cause sodium retention, systemic alkalosis, and allergic reactions.

    Antacids: Drug interactions

    • Decreased absorption of acidic drugs.
    • Chelation with divalent ions, inhibiting the absorption of certain drugs.
    • Alteration in dissolution of pH-sensitive enteric coatings.
    • Urinary alkalinization altering the elimination of many drugs.

    Raft-Forming Agents

    • Non-acid neutralizing.
    • Form a viscous floating layer on gastric contents, preventing acid reflux.
    • Examples include guar gum, xanthan gum, carrageenan, pectin, locust bean gum, and alginates.

    Nausea and Vomiting

    • Nausea: Stomach distress, with distaste for food and an urge to vomit.
    • Vomiting: Disgorging the contents of the stomach, sometimes the small intestine, through the mouth.
    • Vomiting is a natural defense mechanism against poisoning and infection, but can also be a symptom of illness.

    Control of Vomiting

    • Vomiting is a reflex regulated by the central nervous system.
    • The medulla oblongata, the most primitive area of the brain, is responsible for controlling vomiting.

    Control of Vomiting

    • The vomiting center is located in the brain stem and can be activated in two ways: chemical and neural activation.
    • Chemoreceptor trigger zone (CTZ) is located outside the blood brain barrier and is sensitive to toxins and poisons in the bloodstream.
    • Neural activation receives information from the frontal lobes of the brain, digestive tract and balancing mechanism of the inner ear.

    Anti-Emetics

    • Anti-emetic drugs act by restoring normal gastrointestinal motility (prokinetic agents) or preventing signal transmission through the vomiting center.
    • Prokinetic agents include dopamine antagonists such as domperidone and metoclopramide.
    • Dopamine antagonists promote motility by acting on muscular D2 receptors in the lower esophageal sphincter and stomach.
    • Dopamine antagonists can enhance gastric contractions, stimulate gastric emptying, and increase lower esophageal sphincter tone.

    Dopamine Antagonists

    • Domperidone is a peripheral D2 dopamine antagonist that does not cross the blood brain barrier.
    • Metoclopramide is a D2 dopamine antagonist that crosses the blood brain barrier and acts on DA receptors in the CTZ.
    • Metoclopramide also acts as a 5-HT4 receptor agonist, promoting GI motility.

    5-HT3 Antagonists

    • 5-HT3 antagonists, like ondansetron, act in the CTZ and are used for Chemotherapy-induced Nausea and Vomiting (CINV) and gastroenteritis.

    Cannabinoids

    • Cannabinoids, like nabilone, act on CB1 and CB2 receptors in the medulla oblongata and are used for CINV.

    Muscarinic Antagonists

    • Muscarinic antagonists, like hyoscine and scopolamine, act in the vestibular nucleus and vomit center and are used for motion sickness.

    H1 Antagonists

    • H1 antagonists, like diphenhydramine and cyclizine, act in the vestibular nucleus and are used for motion sickness.

    Corticosteroids

    • Corticosteroids, like dexamethasone, can be used for CINV.

    NK1 Antagonists

    • NK1 antagonists, like aprepitant, can be used for CINV.

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    Description

    Test your knowledge on peptic ulcers with this quiz. Discover the recognized causes of peptic ulcers and explore effective therapies for treating peptic ulcer disease. Enhance your understanding of this common gastrointestinal issue.

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