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

de Caestecker, J. BMJ 2001;323:736-739

Pathophysiology

Pathophysiology Multi-factorial Anti-reflux barrier

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

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

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.

“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

Management of GORDDyspepsia not needing referral

Review drugs

Lifestyle advice

Full dose PPI (omeprazole 20mg daily) for 2-4/52

Test and treat for H Pylori

ADD H2 receptor antagonist or prokinetic (metoclopramide)

Review Return to self care

response

response

response

Low dose treatment as required

relapse

response

no response

no response or relapse

no response or relapse

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?

1. What drugs can affect gastric emptying and motility?

2. What other drug options may be useful for GORD?

3. What are the complications of poorly controlled GORD?

4. What lifestyle measures may be useful in GORD?