intro upper GI therapeutics

• common conditions which affect the upper GI tract:

  • functional dyspepsia
  • gastro-oesophageal reflux disease (GORD)
  • peptic ulcer disease (gastric and duodenal ulcers)
• what is functional dyspepsia?

  Persistent, bothersome epigastric pain or burning, early satiation and/or postprandial fullness.

  Disorder of gut-brain interaction

  There is no specific cause that has been identified
• common causes for functional dyspepsia (multifactorial):

  • Abnormalities in GI motility
  • Altered visceral sensitivity (physical and chemical stimuli)
  • Central nervous system processing
  • Psychology (stress, anxiety, depression)
  • Immune function, inflammation, epithelial permeability
  • Changes in microbiome
  • Genetics
• what is GORD?

  • Reflux gastric contents into the oesophagus, oral cavity or lung
  • Can cause chronic cough, and laryngitis.
  • Complications - stricture, Barrett’s oesophagus and oesophageal carcinoma
• common causes for GORD:

  • Obesity
  • Genetic
  • Lifestyle
  • Medication
  • Age
• what is peptic ulcer disease (PUD)?

  • Open sores that develop on the inside lining of oesophagus, stomach or upper portion small intestine
  • Imbalance between agents that protect the epithelium and those which attack
• complications of PUD:

  include upper GI bleed
• peptic ulcers can be further defined by what?

  further defined by location:

  • Gastric (stomach) ulcer
  • Duodenal ulcer
• causes for PUD?

  • Infection with Helicobacter pylori (H. pylori) bacteria
  • Non-steroidal anti-inflammatory drugs (NSAIDS)
• PUD is the most common cause of acute upper GI bleed
• GORD diagnosis:

  • Symptoms including retrosternal (behind the sternum) heartburn and acid reflux (oesophagus)

  Endoscopy (gastroscopy)

  • Non-erosive - symptoms of GORD but the endoscopy is normal
  • Erosive oesophagitis - oesophageal inflammation and mucosal erosions are seen at endoscopy
• Peptic ulcer disease diagnosis:

  • Location - Gastric ulcer and duodenal ulcer
  • Symptoms – well localised (e.g. specific location), midepigastric pain. Constant pain – sharp, stabbing, gnawing
  • Gastric ulcer – pain when stomach empty, relieved by food
  • Duodenal ulcer – pain 2-3 hours after eating, can be worse at night-time

  Endoscopy (gastroscopy)

  • NICE - "Breach in the epithelium of the gastric or duodenal mucosa"
• initial assessment for upper GI symptoms for diagnosis:

  Thorough medical, social and medication history including:

  • Age
  • Location, nature, radiation and severity of pain
  • Associated symptoms
  • Aggravating/relieving factors
  • Checking for red flags including ALARM signs and symptoms
  • Medication history
  • Medical history
  • Social history
• ALARMS - to show upper GI problems

  A - Anaemia (tiredness, shortness of breath)

  L - Loss of weight (unintentional)

  A - Anorexia (unexplained appetite loss)

  R - Recent onset of progressive symptoms or recurrent problems*

  M - Melaena/ haematemesis (blood in stools/vomit)

  S - Swallowing problems (dysphagia)

  Particularly age > 55 with unexplained & persistent recent onset dyspepsia or treatment-resistant dyspepsia
• other red flags for upper GI diseases:

  • Severe, debilitating pain
  • Persistent vomiting
  • Pain awakens person at night
  • Referred (radiating) pain – e.g. pain radiating to jaw/neck/arm
• other investigations that are done when dealing with upper GI diseases include:

  • Blood tests e.g. full blood count
  • Specific tests for specific conditions e.g. Helicobacter pylori, coeliac

  Endoscopy-

  • Visualise specific sections GI tract using a long, thin tube with a camera inside it
  • Gastroscopy – upper GI tract (oesophagus, stomach, part of small intestine)
• non-pharmaceutical management for functional dyspepsia and GORD include:

  Lifestyle measures-

  • Smoking cessation
  • Healthy eating
  • Avoid known precipitants that cause dyspepsia:
  • Fatty, acidic or fried foods and chocolate
  • Reduction or exclusion of alcohol and caffeine
  • Avoid eating late in the evening
  • Reduce caffeine intake
  • Keep alcohol intake to recommended levels
  • Weight reduction
  • Reduce stress
  • Raising the head of the bed/extra pillows (GORD)
  • Regular aerobic exercise (functional dyspepsia)
• Pharmacological Initial management for GORD and functional dyspepsia:

  • Identify potential causative medications and manage appropriately
  • This could include reducing the dose, stopping and/or switching to alternative treatment or continuing alongside acid-suppressing medication
• examples of medications for the initial management for GORD and functional dyspepsia:

  • Antimuscarinics and Anticholinergics
  • Aspirin
  • Benzodiazepines
  • Bisphosphonates
  • Corticosteroids
  • Non-steroidal anti-inflammatory drugs (NSAIDs)
  • Acid-suppressing medicines-
  • lots available as GSL or OTC as well as on prescription
• Proton pump inhibitors:

  • One of the most widely used classes of drugs globally
  • Effective but are often used for longer than needed – side-effects, unnecessary medication burden and resource waste
  • Duration of treatment dependent on indication
  • Generally well tolerated in short term
• side effects of PPIs:

  include constipation, diarrhoea, headache, dizziness (MHRA warning - subacute cutaneous lupus erythematosus)
• long term effects of taking PPIs:

  Achlorhydria (low gastric acid production) associated with increased risk of:

  • Gastric cancer
  • H-pylori infection (particularly in the elderly)
  • Pneumonia
  • Clostridium difficile infection
  • Reduced calcium absorption leading to hip fracture.
• what can we do when prescribing PPIs?

  • Clear indications
  • A lowest effective dose for the shortest period of time + regular review
  • Over 8 weeks PPI use - Consider reducing or stopping unless there is a specific indication for long-term use
  • Consider non-pharmacological management where appropriate
  • Plan to address any rebound or recurrent symptoms
• Helicobacter pylori (H.pylori):

  • Gram-negative bacteria
  • Causes persistent infection in gastroduodenal mucosa
  • Commonest cause PUD - > 90% of DU and > 70% of GU are found to be infected
• Risk factors for NSAID-induced GI injuries:

  History of peptic ulcer, or with two + of the following:

  • Age > 65 years;
  • High dose NSAIDs;
  • Concurrent other medicines that increase the risk of GI adverse-effects e.g. anticoagulants, corticosteroids, selective serotonin reuptake inhibitors
  • Serious co-morbidity e.g. cardiovascular disease, hypertension, diabetes, renal or hepatic impairment
  • Heavy smoker
  • Excessive alcohol consumption
• Peptic ulcer disease - NSAIDs

  Can cause a variety of GI injuries including bleeding and peptic ulceration
• direct mechanisms of NSAID-induced GI damage include:

  • Inhibition of prostaglandin synthesis impairs mucosal defences - erosive breach of epithelial barrier
  • Acid attack deepens breach into frank ulceration
  • Low pH encourages passive absorption of NSAID so trapped in
• indirect mechanisms of NSAID-induced GI damage include:

  • Reduce gastric blood flow
  • Reduce mucus and bicarbonate production
  • This leads to decreased cell repair
• management of NSAID-induced peptic ulcer disease:

  • Stop NSAID if possible
  • Test for H pylori
  • Treat with full dose PPI (or H2-receptor antagonist) for 8 weeks
  • If H pylori is also present – give eradication therapy after above treatment
• If need to continue NSAID after peptic ulcer healed:

  • Discuss potential harm
  • Regular review (at least 6 monthly) appropriateness
  • Reduce dose, prescribe as required, switch to "safer" NSAID e.g. ibuprofen
  • Prescribe "gastroprotection":
  • Acid-suppressing medication – PPI
  • Prostaglandin analogue - misoprostol