Gastro (anki)

• Dyspepsia → non-specific term, group of upper abdominal symptoms

  • Gastro-oesophageal reflux disease (GORD): heartburn & regurgitation
  • Heartburn Gastritis – inflammation of stomach lining (NSAIDs, alcohol)
  • Duodenal ulcers
  • Gastric Ulcers/Peptic Ulcer
  • Functional dyspepsia
• Outline groups of drugs-effects which may lead to dyspepsia:

  • Decreased lower oesophageal sphincter tone
  • Gastric irritations
  • Affect oesophageal sensitivity
• List drugs which may cause dyspepsia via decreased oesophageal sphincter tone:

  • Nitroglycerines (e.g., glyceryl nitrate, isosorbide dinitrate)
  • Anticholinergics (e.g., atropine)
  • Theophylline
  • Beta2 agonists (e.g., salbutamol, terbutaline)
  • Benzodiazepines (e.g., diazepam, nitrazepam, oxazepam)
• List drugs which may cause dyspepsia via gastric irritation

  • Doxycycline
  • Bisphosphonates
  • NSAIDs
  • Iron (ferrous sulphate)
  • Ascorbic acid
  • Steroids
• List drugs which may cause dyspepsia via affecting oesophageal sensitivity

  • Calcium channel blockers
  • phosphodiesterase-5 inhibitors
  • Selective Serotonin Reuptake Inhibitors
  • Tricyclic Antidepressants
• Outline the common aetiologies of dyspepsia:

  • overeating, medicines, pregnancy
  • H.pylori infection
  • delayed gastric emptying
  • function dyspepsia
• Outline the aetiology of dyspepsia associated with overating, medicines and pregnancy;

  
  

  impaired function of the lower oesophageal sphincter pressure
• Outline the aetiology of dyspepsia associated with H.pylori infection:

  
  

  increased acid production > inflammation of the stomach
• Outline the aetiology of dyspepsia associated with delayed gastric emptying increase post-prandial dullness
• Outline the aetiology of dyspepsia associated with functional dyspepsia no specific underlying causes, multifactorial
• Identify alarm symptoms and triggers for referral in relation to the presentation of dyspepsia

  Alarm features include:

  • Unintentional weight loss (>10%)
  • Dysphagia (difficulty swallowing)
  • Odynophagia
  • Melaena (dark sticky stools)
  • Haematemesis (blood in vomit)
  • Unexplained iron deficiency anemia
  • Persistent vomiting
  • Palpable mass or lymphadenopathy
  • Family history of upper gastrointestinal cancer
  • Referred pain
  • Anorexia
• Give non-pharmacological recommendations for dyspepsia Adjusting or stopping drugs that cause symptoms Avoid alcohol, coffee and smoking (or any other triggers) Reducing weight if overweight/obese Reducing meal size (small frequent meals) Drinking fluids between meals rather than with meals Avoid eating 2 to 3 hours before bedtime or vigorous exercise Elevate the head of the bed (night symptoms)
• List medications which may be used in management of dyspepsia

  • Antacids (i.e., aluminum hydroxide, calcium carbonate)
  • Gas-reducing agents, such as those containing simethicone H 2 -receptor antagonists (i.e., cimetidine, nizatidine)
  • PPIs (omeprazole)
  • prokinetic agents ( metoclopramide, domperidone)
  • Antidepressants (i.e., selective serotonin receptor inhibitors, tricyclics)
  • H. pylori therapy/antibiotic therapy (various antibiotic regimens, usually 1 PPI) if H. pylori present
• Describe MOA of combination antacids MOA: neutralize hydrochloric acid secreted by parietal cells
• Describe precautions of combination antacids Renal Impairment CrCl < 10mL/min (risk of accumulation) Phenylketonuria—all Gaviscon® chewable tablets contain aspartame. Heart failure, oedema: sodium-containing antacids causes fluid retention
• Describe common side effects of combination antacids Constipation: aluminum and calcium containing antacids Diarrhoea: Magnesium containing antacids
• Describe practice points of combination antacids Safe to use in pregnancy at usual doses Short duration of action but useful for intermittent or breakthrough symptoms Take between meals ( 1-3 hours after meals)
• Describe MOA of H2 antagonists MOA: Competitively block H2 receptors on parietal cells, reducing gastric acid secretion
• Describe precautions of H2 antagonists Precautions: drug accumulation in renal impairment
• Describe common side effects of H2 antagonists generally well-tolerated Rare: confusion, rash, thrombocytopenia, agranulocytosis, leucopenia, hepatitis, hypersensitivity reactions
• Describe dosage of H2 antagonists GORD: 20 mg twice daily Dyspepsia: 20 mg once or twice daily for 4-8 weeks
• Describe practice points of H2 antagonists Larger doses (up to double) in PUD and GORD is sometimes used by specialists Limited evidence, cost advantages over PPIs may be lost
• Describe MOA of PPIs MOA: irreversibly block gastric H+/K+ATPase (proton pump) in gastric parietal cells. (Acid suppression 24-48 h vs. t½ ~0.5-3 h)
• Describe precautions of PPIs Precautions: PPIs can mask symptoms and delay diagnosis of more serious symptoms Hepatic impairment: risk of accumulation with higher doses Elderly: risk of electrolyte disturbances
• Describe common side effects of PPIs headaches, nausea, vomiting, abdominal pain, constipation, flatulence
• Describe dosage of PPIs GORD/Dyspepsia: 20 mg once daily for 4 to 8 weeks up to twice daily if inadequate response As part of H . Pylori eradication : 20 mg twice daily
• Describe practice points of PPIs Best taken 30 – 60 minutes before a meal (acid pH needed for drug activation) Disperse tablets in water, juice or yoghurt Assess ongoing use regularly after 4-8 weeks of Tx/uncomplicated cases, consider: Stopping treatment Intermittent treatment Step down to lowest effective dose Possible association between long-term PPI use and : decreased serum vitamin B12 concentration, pneumonia, fracture, iron deficiency and chronic kidney disease
• Describe MOA of TCAs in dyspepsia Manipulates pain perception Tx comorbid psychological diseases Enhance gastric accommodation → gastric relaxation
• Describe rationale of TCAs in dyspepsia Psychosocial and psychiatric factors may play an important role in the pathogenesis of functional dyspepsia.
• Describe dosage of TCAs in dyspepsia Amitriptyline 50 mg daily over 10 weeks (Talley et al., 2015) Imipramine 25 mg first 2 weeks, increase to 50 mg thereafter for 12 weeks (Cheong et al. 2018)
• Describe rationale and MOA of Prokinetic therapy in dyspepsia Functional dyspepsia patients often have disorders of gastric motility. Prokinetic therapy improves gastric emptying (enhance esophageal peristalsis) → less time for acid reflux to occur; reduces epigastric discomfort
• Describe dosage regimen of Prokinetic therapy in dyspepsia Domperidone 10 mg orally, up to three times daily before meals as needed
• Describe side effects of Prokinetic therapy in dyspepsia Potential Risk of side effects: prolong QT intervals and risk of arrhythmias in those with CV comorbidities
• Describe evidence of Prokinetic therapy in dyspepsia lack of high-quality data (cisapride and mosapride evaluated in RCTs but not available in Australia) Evidence: TCA > Prokinetic therapy
• describe H. Pylori eradication regimens Triple therapy – 85-90% success rate Non-adherence is an issue H. Pylori resistance to clarithromycin (6-8%) Prior clarithromycin Tx Susceptibility affected with repeated use Resistance to metronidazole much higher (50%) Resistance to amoxicillin is rare
• Outline the Extent of Acid Secretion Inhibition by H2 antagonists reversible inhibitors of H2 receptor. Provide a reversible blockade of H2 receptors. Block 1 of 3 pathways which lead to acid production at pump Inhibit acid secretion by 50-70% maximally. Have a shorter duration of action (typically 6-12 hours).
• Outline the Extent of Acid Secretion Inhibition by PPIs PPI → irreversible inhibitors of proton pump. PPI inhibit both stimulated and basal acid secretion Irreversibly inactivate the proton pump. Achieve a more profound and sustained inhibition of acid secretion (up to 90-95%). Offer longer-lasting effects (typically 12-24 hours).
• Define tau (NtH) tautomer tautomer = structural isomers of chemical compounds that readily interconvert, existing in equilibrium NtH = H on the t position
• Describe how the functional groups attached to the imidazole ring of cimetidine promote the NtH tautomer Cimetidine side chain contains thioamide group (acts as an electron donor → pushing electrons towards the imidazole ring's nitrogen atoms) Promotes the NtH tautomer by: Electron Donation: The thioamide group's electron-donating nature pushes electrons towards the N1 nitrogen of the imidazole ring. Increased N1 Electron Density: This surge in electron density around N1 weakens its attraction to the proton, making the N-H bond (in the N1H tautomer) less stable. N4's Affinity for Protons: C...
• Describe how the NtH tautomer form (of imidazole ring of cimetidine) is essential for effective h3 receptor antagonism Importance of NtH Tautomer for H3 Receptor Antagonism: Structural Similarity to Histamine: The NtH tautomer of cimetidine bears a structural resemblance to histamine, particularly around the crucial nitrogen atoms. Competition for Binding Site: Due to this similarity, the NtH tautomer can effectively compete with histamine for the binding site on the H3 receptor. H3 Receptor Blockade: By competitively binding to the H3 receptor, cimetidine's NtH tautomer hinders histamine fro...