Week 4 – Gastroenterology Clinical Pharmacy Goal: Provide an understanding of complications of chronic liver disease and their management and the current therapeutic strategies for GORD.  Objectives: To enable the pharmacist to:  Be familiar with the clinical features and potential complications of GORD, and the drug and other treatments options available to manage this condition  Understand the underlying mechanisms for the common complications of chronic liver disease, and how these are managed and monitored. 

Gastro-oesophageal Reflux Disease Dr Ian Coombes, University of Queensland + Safe Medication Practice Unit (Adopted from karen Bettanay with permission)

Gastro-Oesophageal Reflux Disease Retrograde flow of gastric contents into oesophagus Only present when reflux of gastric contents causes frequent, severe symptoms or mucosal damage Common disorder causing a variety of symptoms Associated with asthma and oesophageal adenocarcinoma GORD is rarely life threatening but is frequently chronic and relapsing, reducing the quality of life.

Epidemiology ~25% of the adult population in Western society experience symptoms at least monthly 5% experience daily symptoms. Incidence increases with age

Pathophysiology de Caestecker, J. BMJ 2001;323:736-739 Copyright ©2001 BMJ Publishing Group Ltd.

Pathophysiology Multi-factorial Anti-reflux barrier Refluxed material Transient changes in lower oesophageal sphincter (LOS) pressure are normal - GORD have lower LOS pressures, on average. The diaphragm acts as an “external sphincter” and may play an important role. Refluxed material Acid and pepsin damage the oesophageal mucosa, damage proportional to acid exposure Bile acids and pancreatic enzymes probably have a limited role

Oesophageal Defence Mechanisms Oesophageal clearance – gravity and peristalsis; peristaltic dysfunction sometimes occurs in GORD Hiatus hernia can impair oesophageal clearance Saliva contains bicarbonate to neutralize acid. Oesophageal mucosa – mucous, bicarbonate and prostaglandins are protective Ability to repair/heal also important Oesophageal sensitivity (to acid and mechanical stimuli) varies

Investigations for GORD Ambulatory GOR (oesophageal pH) Study (24 hours) (Nov 2004): On maximal antireflux therapy. Proximal oesophagus results: No. of refluxes: 47 No. of long refluxes: 5 Duration of longest reflux: 8 mins Time pH < 4 67 mins % of time pH < 4: 4.7% (normal < 0.1%) DeMeester Score 20.7 (normal <14.72)

Risk Factors Genetic factors Smokers Diet Pregnancy Hiatus hernia Obesity Larger meals, especially late at night High fat content ?Caffeine ?Excess alcohol Pregnancy Hiatus hernia Drugs eg TCA’s anticholinergics, nitrates, ca2+ blockers

Natural history Chronic and relapsing ~80% relapse Highly variable, intermittent or frequent relapses Majority don’t get worse or develop complications Symptoms ≠ oesophageal damage Small percentage develop serious complications-blockage + malignancy

Symptoms Heartburn Retrosternal discomfort Acid brash Water brash Related to meals, lying down, stooping & straining, relieved by antacids Retrosternal discomfort Acid brash Regurgitation acid or bile Water brash Excessive salivation Odynophagia Pain on swallowing may be due to severe oesophagitis or stricture

Atypical symptoms Non cardiac chest pain Dental erosions Respiratory symptoms Chronic hoarseness Laryngitis Chronic cough Asthmatic symptoms: wheeze, SOB Episodic or chronic aspiration can cause pneumonia, lung abscess, and interstitial pulmonary fibrosis. Non-cardiac chest pain caused by GORD has been found in up to 50% of patients with chest pain and normal coronary angiography. Usually there is no relationship to exercise and this helps to differentiate most cases of reflux-induced chest pain from true angina. In 6 to 10% of patients with chronic cough, GORD is the underlying cause. 12

“Alarm Symptoms” -refer Acute gastrointestinal bleeding-refer immediately. Urgent referral for endoscopy for patients of any age with dyspepsia when presenting with any of: Chronic gastrointestinal bleeding Progressive unintentional weight loss Progressive difficulty swallowing Persistent vomiting Iron deficiency anaemia Epigastric mass

Management of GORD Drug treatment first unless alarm symptoms Step down not step up approach PPI (omeprazole) > effect vs H2RA (ranitidine) Long-term trt’ may be required at lowest dose H Pylori test and treat (2/52) if no response PPI + amoxycillin 1 g BD + clarithromycin 500mg bd No evidence of much effect on GORD Increases risk of peptic ulcer or gastric cancer well designed studies have found little or no overall effect of H pylori eradication on GORD.w4 w5 Of more concern is that chronic H pylori infection is associated with an increased risk of peptic ulceration and gastric cancer. For this reason current guidelines recommend H pylori eradication irrespective of potential effects on GORD. 14

Management of GORD Dyspepsia not needing referral Review drugs response Lifestyle advice no response or relapse response Full dose PPI (omeprazole 20mg daily) for 2-4/52 no response or relapse response relapse Test and treat for H Pylori Low dose treatment as required response ADD H2 receptor antagonist or prokinetic (metoclopramide) no response Return to self care Review Fox M, Forgacs I. Gastro-oesophageal reflux disease. BMJ 2006;332:88-93

Step down of PPI therapy Symptoms well controlled Maintain if sev. GORD, strictures, Barrett’s oesophagus Intermittent Evidence good for intermittent symptom driven use in non or mild erosive GORD Surveys show most patients only take as required Take on days when symptoms occur, may need repeated doses t Return for review if becomes continuous Low dose therapy Continuous low dose PPI maintenance controls symptoms in most people who have completed a 4 week course Discuss cessation Chronic use – side effects, increase LFTs, NVD, increase risk of pneumonia, blood dyscrasias

Case 1 52 year old , 98kg obese man PC – worsening of her asthma HPC SOB, coughing nocturnal waking, fevers & sweats for 3/7 Ongoing problem with regurgitation of stomach contents 2 hours after eating, as well as regular N&V PMH includes Asthma GORD for 3 years Social history Lives with wife and 2 children Non smoker Occ alcohol

Case 1 GORD continued Medications Seretide accuhaler 250/50 1 puff bd Ventolin inhaler 2 puffs prn (currently using this qid) Omeprazole 20mg bd Gastrogel 20mL prn Allergies Penicillin → Rash

Investigations for GORD Endoscopy (Jan 2004): Large sliding hiatus hernia with very lax gastro-oesophageal junction. Moderate ulceration within hernial sac. No reflux oesophagitis. Suggest trial of vigorous anti-reflux therapy. Oesophageal motility report (Nov 2004): Normal oesophageal peristaltic motility

Diagnosis and Plan Worsening of asthma ?infective Possible worsening of GORD Treat with clarithromycin 250mg bd For gastroenterology review

Questions? What drugs can affect gastric emptying and motility? What other drug options may be useful for GORD? What are the complications of poorly controlled GORD? What lifestyle measures may be useful in GORD?