Diese Präsentation wurde erfolgreich gemeldet.
Die SlideShare-Präsentation wird heruntergeladen. ×

Final NSAIDs Induced Gastropathy.pptx

Wird geladen in …3

Hier ansehen

1 von 35 Anzeige

Weitere Verwandte Inhalte

Ähnlich wie Final NSAIDs Induced Gastropathy.pptx (20)


Final NSAIDs Induced Gastropathy.pptx

  1. 1. NSAIDs Induced Gastropathy & its management Nonsteroidal anti-inflammatory drugs (NSAIDs)
  2. 2. What are NSAIDs NSAIDs are more than just pain relievers. They also help reduce inflammation and lower fevers. They prevent blood from clotting, which is good in some cases but not so beneficial in others. NSAIDs are used to treat a variety of symptoms such as pain, inflammation, and stiffness caused by rheumatoid arthritis and tendonitis.
  3. 3. NSAIDs and their classification Classification of NSAIDs Types Chemical composition Common NSAIDs Salicylates Salicylates Derivatives of 2- hydroxybenzoic acid (salicylic acid) Aspirin, diflunisal, and salsalate Propionic acid derivatives or “profens” Derivatives of arylacetic acids Ibuprofen, dexibuprofen, ketoprofen, dexketoprofen, naproxen, fenoprofen, flurbiprofen, oxaprozin, and loxoprofen Acetic acid derivatives Derivatives of acetic acids Indomethacin, diclofenac, nabumetone, tolmetin, sulindac, etodolac, and ketorolac Enolic acid derivatives or oxicams Derivatives of 4-hydroxy benzothiazine heterocycle Piroxicam, isoxicam, meloxicam, tenoxicam, droxicam, and lornoxicam Fenamic acid derivatives or fenamates Derivatives of anthranilic acid Mefenamic acid, flufenamic acid, tolfenamic acid, and meclofenamic acid Phenylpyrazolones Derivatives of 1-aryl-3,5- pyrazolidinedione Phenylbutazone, oxyphenbutazone COX-2 selective inhibitors Diaryl-5-membered heterocycles Celecoxib, rofecoxib, and valdecoxib Anilides and sulphoanilides Acetamides of aniline with or without a 4-hydroxy or 4-alkoxy group Acetaminophen, phenacetin, and nimesulide Current perspectives in NSAID-induced gastropathy. Mediators of inflammation. 2013; 2013
  4. 4. NSAIDs in patient management NSAIDs are used for three broad symptom types that occur in a range of conditions: High temperature or fever Inflammation Pain NSAIDs play a role in the treatment of many different conditions that involve inflammation, pain or both. Which includes: Rheumatoid arthritis Ankylosing spondylitis Psoriatic arthritis Reactive arthritis Acute gout Period pain Metastatic bone pain Osteoarthritis Headache and migraine Post-operative pain Pain due to inflammation and tissue injury Renal colic Anti-platelet properties
  5. 5. Risk factors for GI complications associated with NSAID Journal of Pain Research 2018:11 361–374
  6. 6. Relative risk of upper-GI complications with different NSAIDs Journal of Pain Research 2018:11 361–374
  7. 7. The most commonly used drugs in Trauma practice, for pain relief are Non-Steroidal anti inflammatory drugs (NSAIDs) According to Orthoinfo.aaos.org/topic.cfm?topic=a00284
  8. 8. NSAIDs Misuse and it’s impact More than 30 million people take nonsteroidal anti-inflammatory drugs (NSAIDs) each day. This number has grown significantly with increasing use of OTC and prescription NSAIDs, low-dose aspirin, and after reports of their potential antineoplastic effects. The efficacy of NSAIDs as anti-inflammatory analgesics is not in doubt, but their adverse events are problematic. These relate mainly to cardiovascular, renal, hepatic, and gastrointestinal tissues. Gastroenterology. 2018 Feb 1; 154(3): 500-14
  9. 9. NSAIDs Misuse and it’s impact In a study aimed to determine the prescribing practice of multiple NSAIDs in Pakistan by healthcare practitioner and their attitude towards patient life safety and what consequences are responsible for irrational practice of these most common OTC drug, their findings were: Journal of Scientific and Innovative Research. 2014; 3(2): 148-54
  10. 10. Impact of misuse on GI The cardiovascular adverse events have recently received much attention, but the frequency and severity of the gastrointestinal damage continues to cause concern. Accordingly, gastroduodenal ulcer rates range from 5% to 80% in short-term endoscopy studies and from 15% to 40% in long-term users. NSAIDs also damage the small intestine as many as 70% of long-term users of NSAIDs have small intestinal inflammation, and 30% have erosions or ulcers. The gastric and small bowel damage is associated with various management problems and, at times, life-threatening complications, such as bleeding, strictures and perforations. Gastroenterology. 2018 Feb 1; 154(3): 500-14
  11. 11. NSAIDs or no NSAIDs Gastrointestinal effects of NSAIDs and coxibs. Journal of Pain and Symptom Management. 2003 Feb 1;25(2):32-40
  12. 12. NSAID induced GI complications There are mainly three different mechanisms of NSAID induced GI complications: Inhibition of enzyme COX- 1 and gastroprotective PG Membrane permeabilization Production of additional pro-inflammatory mediators. Current perspectives in NSAID-induced gastropathy. Mediators of inflammation. 2013; 2013
  14. 14. Standard-dose PPIs are recommended for patients taking ns- NSAIDs at risk for upper-GI complications (bleeding and perforation) and for those having had an episode of previous GI bleeding and prescribed selective COX2 inhibitors. In both ns- NSAID and COX2-selective NSAID users, PPI therapy reduces upper-GI symptoms, in particular dyspepsia. Appropriate use of PPIs: recommendations from international guidelines 2016 Position paper on safe PPI use Journal of Pain Research 2018:11 361–374
  15. 15. The 2017 update recommends that patients take long- term PPIs for NSAID bleeding prophylaxis if at high risk Appropriate use of PPIs: recommendations from international guidelines American Gastroenterological Association clinical practice updates 2017 Journal of Pain Research 2018:11 361–374
  16. 16. In patients with NSAID-associated bleeding ulcers who must resume NSAIDs, it is recommended to give a daily PPI together with a COX2- selective NSAID at the lowest effective dose. In patients with low-dose aspirin-associated bleeding ulcers that have been resumed on aspirin for secondary prevention, long-term daily PPI therapy should also be provided Appropriate use of PPIs: recommendations from international guidelines American College of Gastroenterology guidelines on management of bleeding ulcers Journal of Pain Research 2018:11 361–374
  17. 17. In patients using NSAIDs with diagnosed peptic ulcers, a full-dose PPI or H2RA for 8 weeks should be offered and NSAIDs should be stopped where possible. In high-risk patients (previous ulceration) for whom NSAID continuation is necessary, a PPI together with the NSAID should be prescribed. Appropriate use of PPIs: recommendations from international guidelines National Institute for Health and Care Excellence 2014 guidelines on the investigation and management of gastroesophageal reflux disease and dyspepsia in adults Journal of Pain Research 2018:11 361–374
  18. 18. Expert consensus document on reducing the risks of antiplatelet therapy and NSAID use states that PPIs are the preferred gastroprotective agent for the treatment and prevention of GI toxicity associated with NSAIDs and aspirin Recommendations - Risks of antiplatelet therapy and NSAID use
  19. 19. Therapies for prevention of Gastric Damage
  20. 20. Current perspectives in NSAID-Induced Gastropathy Several clinical practice guidelines have proposed different approaches for controlling the GI complications associated with NSAIDs. A number of strategies have been recommended by American College of Gastroenterology to decrease NSAID-induced GI damage including use of: Selective cyclooxygenase-2 inhibitors, Co-administration of gastroprotective agents like misoprostol PPIs, or histamine-2 receptor antagonists. Current perspectives in NSAID-induced gastropathy. Mediators of inflammation. 2013; 2013
  21. 21. As per the guidelines, PPIs recommended for gastroprotective therapy to the patients on thienopyridines and NSAIDs. Current perspectives in NSAID-induced gastropathy. Mediators of inflammation. 2013; 2013 Current perspectives in NSAID-Induced Gastropathy
  22. 22. S Afr Pharm J 2012;79(4):12-18 Current perspectives in NSAID-Induced Gastropathy
  23. 23. Clinician’s Guide The use of proton pump inhibitors in treating and preventing NSAID- induced mucosal damage. Arthritis research & therapy. 2013 Jul 1;15(S3):S5
  24. 24. Method to prevent Peptic ulcer and Mucosal injury in patients taking NSAID Lanza et al. Am J Gastroenterol 2009; 104:728 – 738 • Although co-therapy with a standard-dose H2RA may prevent duodenal ulcers, it has not been shown to prevent NSAID- related gastric ulceration. • Enteric coating or buffering of NSAIDs and co-therapy with sucralfate have not been shown to be effective in preventing NSAID-related gastric or duodenal ulceration
  25. 25. Clinical References
  26. 26. The risk of Gastroduodenal ulceration associated with Non-steroidal anti- inflammatory drugs (NSAIDs) can be reduced by 75% in healthy individuals, if they take Omeprazole 20 mg daily According to study published in US Doctor’s Guide of Gastroenterology Oct 2007 75%
  27. 27. ENSURING GUT PROTECTION The efficacy of omeprazole in the treatment of acid-related disorders is well established. Clin Drug Investig 2012; 32 (4): 221-233
  28. 28. OMNIUM TRIAL OMNIUM (Omeprazole versus Misoprostol for NSAID-induced Ulcer Management) The remission rate was significantly higher with OMEPRAZOLE than with the comparator Clin Drug Investig 2012; 32 (4): 221-233
  29. 29. Design: 6 month randomized, double blind, controlled trial. Setting: 93 clinical centers in 14 countries. Patients: 935 patients who were 18–85 years of age; had conditions that required continuous treatment with at least a minimal dose of oral or rectal NSAIDs; and had ulcers ⩾3 mm in diameter in stomach, duodenum, or both, or >10 gastric or duodenal erosions. Ref: Hawkey CJ, Karrasch JA, Szczepañski L, et al. (1998) . N Engl J Med Omeprazole (OM) vs. Misoprostol (MIS) for ulcers associated with non-steroidal anti-inflammatory drug use
  30. 30. Hawkey CJ, Karrasch JA, Szczepañski L, et al. (1998) . N Engl J Med Omeprazole 20 mg is was more effective than Misoprostol Omeprazole (20 mg/day) was more effective and better at maintaining remission than Misoprostol (400 μg/day). Misoprostol caused more adverse events during treatment.
  31. 31. BioMed Research International Volume 2014, Article ID 693567, 7 pages Comparison of Proton Pump Inhibitor and Histamine-2 Receptor Antagonist in the Prevention of Recurrent Peptic Ulcers/Erosions in Long-Term Low-Dose Aspirin Users The 24-week clinical outcomes of the patients using low-dose aspirin for cardiovascular protection with a history of ulcers/erosions and co-therapy of Omeprazole or Famotidine were retrospectively reviewed. Design: Retrospective cohort study Study design: Total 104 patients (Famotidine group: 49 patients, Omeprazole group: 55 patients) Dosage: • Aspirin 75 to 325 mg daily (For primary or secondary prevention of coronary artery disease or cerebral vascular accident) • Concomitant use of Famotidine 40 mg daily or Omeprazole 20 mg daily
  32. 32. Omeprazole is superior to Histamine-2 Receptor Antagonist 49% 49% less gastrointestinal symptoms with the use of Omeprazole 20mg 70% 70% less recurrent ulcers/erosions with the use of Omeprazole 20mg Ref: BioMed Research International Volume 2014, Article ID 693567, 7 pages
  33. 33. COX-2 NSAIDs versus conventional NSAIDs plus PPIs Trial Design • 287 H. Pylori Negative patients whose Bleeding peptic ulcer has healed. • Recurrent bleeding over 6 months observation Celecoxib 200mg BD (s-NSAID) + Placebo Scheiman Arthritis Research & Therapy 2013, 15(Suppl 3):S5 Diclofenac 75mg (ns- NSAID) + Omeprazole 20mg OD 4.9% recurrent bleeding 6.4% recurrent bleeding A number of observational studies have provided support for the value of PPI gastroprotection as an alternative approach to the use of a COX-2 specific inhibitor.
  34. 34. RISK REDUCTION IN ULCER BLEEDING COMPARED TO COX-2 INHIBITORS In a large Tennessee Medicaid database, investigators found: Concurrent users of NSAIDs and PPIs had a 54% (27 to 72%) risk reduction in ulcer bleeding, very similar to the 50% (27 to 66%) reduction for concurrent users of PPIs and COX-2 selective inhibitors Scheiman Arthritis Research & Therapy 2013, 15(Suppl 3):S5
  35. 35. 1 NSAIDs are the major cause of Upper GI erosion, ulcers and bleeding 2 Omeprazole 20mg OD with NSAID is effective therapy for upper GI erosions, ulcers and bleeding cases 3 Co-therapy with Omeprazole 20mg is effective therapy to prevent GI problems Key Points

Hinweis der Redaktion

  • Inflammation is the immune system's response to infection and injury. Heat, redness, swelling, and pain are noticeable signs of inflammation.

    The body receives pain signals from nerve receptors when inflammation occurs. These signals result from complex responses and interactions between cells and chemicals in the body.
    Anti-inflammatory drugs reduce pain partly by reducing inflammation. People can use these drugs to relieve symptoms of pain, stiffness, swelling, and fever.

    Non-steroidal anti-inflammatory drugs (NSAIDs) are medications used regularly in the treatment of arthritis and intermittently for fever, pain and headache.

    They are most commonly used systemically, usually as an oral formulation but can also be used as a suppository or administered by intramuscular injection. Topical gels and creams containing NSAIDs may be applied to sports injuries, painful joints and, most recently, for the treatment of solar (actinic) keratoses (sun spots). NSAIDs are taken by children and adults. 

  • In low doses, aspirin is used to help prevent artery disease that can lead to heart attack or stroke. It may also be used to reduce the risk of some types of colorectal cancer.

    Headache and lower back pain are two of the more common reasons for using NSAIDs. If these problems become long-term issues, patients should consider the safety of using NSAIDs.
  • Prescription collected were mostly from emergency (80%) and general physicians (20%)
  • https://www.sciencedirect.com/science/article/pii/S0016508517366660

    Studies found that gastric and small bowel mucosal prostaglandins could be decreased by 95%-98% without mucosal damage, and confirmed in COX1- knockout mice. Short-term loss or inhibition of COX2 does not cause damage, but small bowel damage is evident in mice and humans exposed to NSAIDs for long periods of time. Dual inhibition of COX1 and COX2 causes gastric and small bowel lesions, albeit somewhat less severe than the lesions caused by conventional acidic NSAIDs.
  • Epidemiologic studies indicate that NSAID use increases the risk of GI complications 2–6 times. Studies of large population cohorts (Tayside, Scotland; Odense, Denmark; Tennessee Medicaid patients >65 years of age) suggest an excess of serious clinical upper GI events due to NSAID use of 0.2% to 1.25% per year among these “general” populations. Large, prospective outcome studies in large numbers of arthritis patients suggest an annual incidence of serious upper GI complications (major bleeding, perforation, obstruction) of approximately 1–1.5% and of clinical upper GI events (complications plus symptomatic ulcers discovered on evaluation of GI symptoms or signs) of approximately 2.5–4.5%.
  • OMNIUM (OmeprazoleversusMisoprostolforNSAID-induced Ulcer Management)
    OPPULENT (Omeprazole versus Placebo as Prophylaxis of Ulcers and Erosions from NSAID Treatment)
    SCUR (Scandinavian Collaborative Ulcer Recurrence) studies
  • The incidence of gastrointestinal symptoms, recurrent ulcers/erosions, erosive esophagitis, gastrointestinal bleeding, and thromboembolic events was analyzed.