1. 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. 

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

3. 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.

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

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

6. 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

7. 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

8. 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 < mins
% of time pH < 4: 4.7% (normal < 0.1%)
DeMeester Score (normal <14.72)

9. 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

10. 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

11. 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

12. 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

13. “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

14. 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

15. 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

16. 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

17. 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

18. 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

19. 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

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

21. 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?