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Proton Pump Inhibitors A Curate’s Egg?

Proton Pump Inhibitors A Curate’s Egg?. Dr John O’Malley MA MB ChB MRCGP. www.pcsg.org.uk. Join. Meetings, journal, website access ALL FREE !!!!!!!!!!!!!!!. This f***ing egg is off!. This is a fantastic drug. It has an important role in treating x .

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Proton Pump Inhibitors A Curate’s Egg?

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  1. Proton Pump InhibitorsA Curate’s Egg? Dr John O’Malley MA MB ChB MRCGP

  2. www.pcsg.org.uk Join Meetings, journal, website access ALL FREE !!!!!!!!!!!!!!!

  3. This f***ing egg is off!

  4. This is a fantastic drug It has an important role in treating x Why didn’t we realise it has horrendous side effects?

  5. PPIs • £1 billion NHS costs • Globally £40 Billion

  6. Pharmacology • Unstable at acid ph • Parietal cell not stomach activation • Act by forming a irreversible bond with cysteine residues in the proton pump • Short pharmacological half life

  7. Pharmacology 2 • But.... Lasts for 24 hours • No tachyphylaxis

  8. The Proton Pump H2 Antagonists Text Text Atropine Proton Pump Inhibitors

  9. Good bits

  10. Dyspepsia • Reflux • Barretts/? Prevention of cancer • Prevention of strictures • Diagnostic test • Upper GI bleeding • Ulcer prophylaxis in NSAIDs and aspirin • Ulceration/ HP eradication • Zollinger Ellison Syndrome

  11. And the bad bits?

  12. Side effects • Slow response • Headaches • Rashes • Diarrhoea • Abdominal pain • Flatulence • Interactions

  13. Problems • Interstitial nephritis • Osteoporosis • Vitamin B12 absorption • C. Diff and other infections • Microscopic colitis • Inappropriate investigation and referral

  14. And when we should, we don’t

  15. Underuse • Gastroprotection • Oesophageal strictures • ? Barrett’s oesophgus

  16. Gastroprotection

  17. NICE 2001 • Recommendations for patients for whom a regular NSAID is absolutely necessary: • Patients at any age with existing cardiovascular disease, including patients on low dose aspirin: Standard NSAID e.g. ibuprofen, diclofenac or naproxen +misoprostol or PPI if misoprostol not tolerated. • Patients aged 65+ with no cardiovascular risk factors and not onaspirin: • Consider Cox-II selective inhibitor (not sure on that one!) • All other patients i.e. patients < 65 with no other risk factors*: • • Standard NSAID e.g. ibuprofen or diclofenac

  18. Risk factors for GI complications withNSAIDs • Age • Previous ulcer, bleed or perforation • Concomitant drug treatment (steroids,anticoagulants, SSRIs) • Co-morbidity (CVD, renal and hepatic impairment, etc.) • Rheumatoid Arthritis • NSAID dosage and duration.

  19. HP eradication Maastricht -3 2005 • Chronic NSAID users • Naive NSAID users – test and treat • Long term aspirin users – test and treat • PPI is superior in preventing ulcers

  20. Risk of NSAID related gastrointestinalbleeding by age for population 100,000 Anon. Cox-2 roundup. Bandolier 2000;75

  21. ACUTE Vs CHRONIC NSAIDUSE

  22. SSRIs AND UGIH • “Our meta-analysis shows that SSRIs • more than double the risk of UGIH and • concomitant NSAID use increase the risk • of UGIH by 500%” Loke et al. Alim. Pharm. Therapeutics 2007

  23. SSRIs: NUMBER NEEDED TOHARM

  24. SSRIs and NSAIDs

  25. Do PPIs work?

  26. Number needed to treat to avoid a peptic ulcer in elderly NSAID/aspirin users...........

  27. 3

  28. Compliance - GPs “In individual studies in primary care adherence to prescribing guidelines varied from 9% to 27%.”

  29. Compliance - patients “...adherence to NSAID plus PPI or H2RA declined rapidly, so that after 6 months the majority of patients were not taking gastroprotection prescribed.” Moore et al. BMC Musculoskeletal Disorders 2006; 7:79

  30. Cost

  31. Omeprazole cost • 28 days of 20mg/day =£1.62

  32. Conclusion • Right person with the right drug gives the right outcome

  33. Problems • Interstitial nephritis • Osteoporosis • Vitamin B12 absorption • C. Diff and other infections • Microscopic colitis • Inappropriate investigation and referral

  34. Interstitial nephritis

  35. Interstitial nephritis • 15% of all acute admission with acute kidney damage • Immune mediated? • Can lead to severe kidney damage • Who checks kidney function?

  36. Osteoporosis • UK study (GPRD) • 13,556 patients with hip fracture • Risk 1.4 after using PPI for >1 year • Risk 2.65 if long term high dose

  37. Causal? • Reduces absorption of dietary calcium • Inhibits magnesium absorption • Also inhibit osteoclasts • ? Prevent osteoporosis • Coincidental?

  38. Iron deficiency • Iron absorption • ? Long term, high dose PPI link • Theoretical but not proven

  39. Vitamin B12 Deficiency • B12 bound to protein • Pepsin needed • B12 levels reduced but significant deficiency?

  40. Infections • PPI use and Salmonella/ campylobacter

  41. Clostridium Difficile infection • Gram positive bacteria • Anaerobic spore forming • Severe diarrhoea • Can lead to pseudomembranous colitis • Toxic megacolon • Absent gut flora

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