MPharm Programme Management of Dyspepsia Slide 1 of 28
Learning Objectives Understand the principles and wider implications underpinning evidence based therapeutics in the key clinical specialities Objectively analyse the rationale underlying the treatment of disease, including pharmacological therapy and non-pharmacological therapy, with consideration of the evidence base, underpinning scientific principles, cost and political agenda around healthcare Assess and critically appraise patients medication regimens, including related calculations, identify areas in which improvements to care may be made and propose suitable solutions Assess and evaluate the signs and symptoms of illness employing appropriate examination skills, determine if a treatment intervention is warranted or referral to an alternative health professional Slide 2 of 28
Aims Look at dyspepsia, GORD, PUD and H. Pylori What are they? Potential causes How can they be diagnosed? Treatment options Patient considerations Slide 3 of 28
Dyspepsia Dyspepsia is a complex of symptoms: Epigastric pain Bloating Heartburn Pain worse/better with eating Dyspeptic symptoms are a poor predictor of significant disease Slide 4 of 28
Dyspepsia Initial diagnosis: uninvestigated dyspepsia Common (40% of UK population) Related to lifestyle Widespread endoscopy is unlikely to benefit patients Slide 5 of 28
Key points of NICE guidelines updated in Sept 14 Managing dyspepsia presenting to the community pharmacist Referral criteria for endoscopy Test and treat H-pylori Management of uninvestigated dyspepsia (patients for whom an endoscopy is not required) Slide 6 of 28
Key points of NICE guidelines For patients who have an endoscopy they may be given a diagnosis of either: Functional dyspepsia (Functional dyspepsiais definedas the presence of dyspepticsymptoms in the absence of an organic cause that readily explains them) Gastro-oesophageal reflux disorder (GORD) Peptic ulcer disease (PUD) Malignancy Slide 7 of 28
Community Pharmacy Offer initial and ongoing help for people with symptoms of dyspepsia. This includes advice about lifestyle changes, using over-thecounter medication, help with prescribed drugs Healthy eating, weight reduction and smoking cessation Avoid precipitants: smoking, alcohol, coffee, chocolate, fatty foods and being overweight Slide 8 of 28
Medications related to dyspeptic symptoms In all presentations of dyspepsia, review medications for possible causes of dyspepsia calcium antagonists nitrates theophylline bisphosphonates corticosteroids non-steroidal anti-inflammatory drugs NSAIDs Antiplatelets Anticoagulants Slide of 28
Who should undergo an endoscopy? People presenting with dyspepsia together with significant acute gastrointestinal bleeding -referthem immediately (on the same day) to a specialist Slide 10 of 28
Who should undergo an endoscopy? ALARM symptoms An urgent referral for endoscopy or to a specialist (as appropriate) should be made for patients of any age with dyspepsia who present with any of the following: Chronic gastro-intestinal bleeding Dysphagia Progressive unintentional weight loss Persistent vomiting Iron deficiency anaemia Epigastric mass Suspicious barium meal result Slide 11 of 28
Who should undergo an endoscopy? In patients aged 55 years and older with unexplained and persistent recent onset dyspepsia alone -an urgent referral for endoscopy should be made In patients aged less than 55 years, endoscopic investigation of dyspepsia in the presence of alarm symptoms Slide 12 of 28
Endoscopy Endoscopy for absolute diagnosis Endoscopy not always a viable option ALARM signs Patients undergoing endoscopy should not take a proton pump inhibitor (PPI) or an H 2 -receptor antagonist (H 2 RA) for a minimum of two weeks beforehand. Slide 13 of 28
If a patient has not met the referral criteria for endoscopy. They are referred to as having uninvestigated dyspepsia This is treated as follows: 1. Offer empirical full dose PPI therapy for 4 weeks 2. Offer H-pylori test and treat (see later for these guidelines) 3. If symptoms return maintenance PPI or as required 4. Offer H2 receptor antagonist if there is inadequate response to PPI Slide 14 of 28
Possible diagnosis after endoscopy Functional dyspepsia (Functional dyspepsiais definedas the presence of dyspepticsymptoms in the absence of an organic cause that readily explains them) Gastro-oesophageal reflux disorder (GORD) Peptic ulcer disease (PUD) Malignancy Slide 15 of 28
GORD Dysfunction of lower oesophageal sphincter...reflux of gastric acid Symptoms Heartburn, belching, excessive salivation, painful swallowing Causes/ associations Smoking, alcohol, hiatus hernia, pregnancy, obesity, drugs, (TCA, nitrates, anticholinergics) Can lead to oesophagitis Slide 16 of 28
GORD Offer people with GORD full dose PPI for 4-8 weeks Can then step down to maintenance PPI if needed at lowest effective dose H2RA if inadequate response to PPI Oesophagitis Full dose PPI for 8 weeks to heal If fails switch to another PPI Full dose PPI may be needed as maintenance Slide 17 of 28
Peptic Ulcer Disease Medication Review - Stop NSAIDs if used 5% DU & 70% GU associated with H. pylori if +ve and not NSAID associated: eradication therapy if +ve andnsaid associated: full-dose PPI for 2 months followed by eradication therapy if -ve: full-dose PPI for 1 2 months Other drugs? GU: repeat endoscopy & re-test for H. pylorito confirm healing and eradication DU: re-testing not routinely required Consider low-dose PPI as required for relapse Slide 18 of 28
Peptic ulcer disease Offer H pylori eradication therapy to people who have tested positive for H pylori and who have peptic ulcer disease For people using NSAIDs with diagnosed peptic ulcer, stop the use of NSAIDs where possible. Offer full dose PPI for 8 weeks Repeat endoscopy and H-pylori testing may be indicated Slide 1 of 28
NSAID associated ulcers GI bleeding and ulceration can occur with NSAID use The risk of serious upper GI side effects varies between NSAIDs Whenever possible NSAID should be withdrawn if an ulcer occurs Patients at high risk of developing GI complications with an NSAID include: Over 65 History of peptic ulcer disease Taking other medications which increase the risk of GI side effects (think interactions!) Those with serious co-morbidity Can use PPI protection in these patients if an NSAID is needed (switch to lower risk non-selective NSAID or Cox 2 selective (think CV risks discussed later in the term) alternatively misoprostol or double dose H2 antagonists If need to continue NSAID after an ulcer again these procautionsmay be put in place. Slide 20 of 28
Functional dyspepsia Test and treat H pylori If H pylori has been excluded and symptoms persist low dose PPI or an H2RA for 4 weeks Slide 21 of 28
Helicobacter Pylori Eradication: cures PUD may reduce the risk of gastric cancer may help functional dyspepsia does not improve or aggravate GORD 13 C-urea breath tests and stool antigen tests are preferred to lab-based serology 13 C-urea breath tests to confirm eradication if necessary Slide 22 of 28
Helicobacter Pylori Before testing: no antibacterials for 4 weeks no antisecretory drugs for 2 weeks fast for at least 6 hours (breath test) Slide 23 of 28
Urea Breath Test HP urease breaks down ingested labelled urea, patient exhales labelled bicarbonate 4-8% accurate To avoid mistaking bacterial suppression with eradication, the UBT must be delayed at least 4 weeks after completing therapy Slide 24 of 28
Urea Breath Test Advantages Endoscopy not required Less expensive than endoscopy Non-endoscopic method to confirm HP eradication Disadvantages Potential for false negative results after antibiotics, bismuth, PPIs Results are not immediate (2 days) Slide 25 of 28
Rapid Urease Urease of HP generates ammonia, which causes a colour change Sensitivity and specificity > 0% Advantages Test of choice at endoscopy High specificity and sensitivity Easily performed Rapid results Disadvantages Requires endoscopy Patient discomfort Expensive (includes endoscopy) Antibiotics, bismuth, and PPIs can cause false-negative results Slide 26 of 28
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Eradication of H-pylori First line treatment 7 day twice daily course of: PPI Amoxicillin Either clarithromycin or metronidazole (no amoxicillin for allergic patients) Other options bismuth, tetracycline, quinolone Slide 28 of 28
Eradication of H-pylori Treatment failure usually indicates antibacterial resistance of poor compliance Resistance to amoxicillin is rare but common to metronidazole and clarithromycin 2 week course may improve eradication however greater risk for side effects and poor compliance. Slide 2 of 28
Prescribing points: Proton Pump Inhibitors Key safety points: Can increase the risk of fractures particularly in the elderly if used at high doses for over a year risk increased in smokers Can increase the risk of GI infections clostridium difficile Many secondary care trusts have a policy to withhold PPI during treatment with antibiotics May mask signs and symptoms of gastric cancer Care in those presenting with alarm symptoms rule out malignancy before treatment is started Slide 30 of 28
PPIs and fracture risk Unadjusted cross-sectional fracture risk at baseline for PPI users and nonusers Nature.com Limit duration and dosage if possible to reduce risk monitor during long term risk Slide 31 of 28
Prescribing points: Proton Pump Inhibitors Monitoring requirements: Measurement of serum magnesium concentrations should be considered before and during prolonged treatment particularly during prolonged treatment or used with other drugs which can cause hypomagnesaemia or with digoxin Can also rarely cause hyponatraemia Slide 32 of 28
Prescribing points: Proton Pump Inhibitors MRHA advice: In light of the most recent evidence, the previous advice on the concomitant use of clopidogrelwith proton pump inhibitors has now been modified. Use of either omeprazole or esomeprazole with clopidogrelshould be discouraged. The current evidence does not support extending this advice to other PPIs Check that patients who are taking clopidogrel are not buying over-thecounter omeprazole No such interaction noted for H2RAs and Antacids Discourage concomitant use of other known CYP2C1-inhibiting medicines with clopidogrelbecause these are expected to have a similar effect to omeprazole and esomeprazole (CYP2C1 inhibitors include fluvoxamine, fluoxetine, moclobemide, voriconazole, fluconazole, ticlopidine, ciprofloxacin, cimetidine, carbamazepine, oxcarbazepine, and chloramphenicol). Slide 33 of 28
Mechanism of interaction? Clopidogrel converted to active metabolite via CYP450 enzyme system Omeprazole inhibits CYP450 enzyme system Slide 34 of 28
However new reviews of this interaction Pharmacokinetic and pharmacodynamic studies have suggested that all PPIs inhibit these isoenzymes to different degrees and therefore could affect the clinical efficacy of clopidogrel There have been no randomised trials to date which have been specifically designed to assess the effect of PPIs on clinical outcomes in patients taking clopidogrel Secondary analyses of the COGENT, TRITON-TIMI 38 and PLATO trials have not shown an increased risk of major adverse cardiovascular events in patients taking PPIs and clopidogrel together Slide 35 of 28
However new reviews of this interaction Treatment decisions regarding concomitant use of clopidogrel and PPIs must balance the overall risks and benefits and consider the risk of cardiovascular and gastrointestinal complications in individual patients. In some patients the benefits of PPI may outweigh the risk of reduced clopidogrel efficacy Not enough evidence for a clinically meaningful interaction and that PPIs should not be withheld in patients on clopidogrelif they are clinically needed. Slide 36 of 28
However new reviews of this interaction The FDA, MHRA and EMA currently advise avoiding omeprazole and esomeprazole in patients taking clopidogrel There is insufficient evidence available regarding which PPI is least likely to interact, however based on data from pharmacokinetic and pharmacodynamic studies and the small amount of data available from the COGENT study, the FDA suggest that pantoprazole is the least likely to interact investigate this. Slide 37 of 28
Summary key information you need a good working knowledge of: ALARM symptoms Differential diagnosis How to treat H-pylori PPI prescribing points Safety re NSAIDs expanded on later in the term Slide 38 of 28
References NICE Clinical Guideline 184: Dyspepsia and gastrooesophageal reflux disease: investigation and management of dyspepsia, symptoms suggestive of gastro-oesophageal reflux disease or both (September 2014) BNF: Chapter 1 Gastro-intestinal system NICE: Clinical Knowledge Summaries Do proton pump inhibitors reduce the clinical efficacy of clopidogrel? Prepared by UK Medicines Information (UKMi) pharmacists for NHS healthcare professionals Date prepared: 2nd November 2012 Slide 3 of 28