GI Clinical Pearls

1. GI Clinical Pearls

2. Clinical Pearls • Upper GI Diseases • PPI Therapy • Lower GI Diseases • Colon - C. diff • Hepatology • Ammonia Levels • Pain Management

3. Case #1 – Acid Reflux 56M resolved acid reflux and heart disease PMHx – CAD with stent on Clopidogrel Presents to clinic for recommendations Currently on PPI therapy What would you advise? A. Stop PPI immediately – reflux has resolved B. Stop PPI & Use H2 blockers PRN for one week C. Taper off PPI – take every other day PRN D. Stop PPI due to interaction with Clopidogrel

4. PPI: Mechanism of Action PPI are activated in the acidic compartments of parietal cells THUS, they only inhibit actively secreting proton pumps IRREVERSIBLY block the proton pump until new molecules synthesized (24-48 hours)

5. Proton Pump Functioning K+ K+ K+ K+ H+ H+ H+ H+ After activation, the parietal cell undergoes a series of changes,allowing proton pumps to reach the surface of the parietal cell1 Proton pumps become activated in response to food1 Only active proton pumps can secrete acid1 However, not all pumps become activated1,2 H2 Unstimulated proton pumpsin cytoplasmic tubules ATPase Active proton pumps Unstimulated proton pumps ACh ATPase H2 = Histamine ACh = Acetylcholine Gastrin Inactive Parietal Cell Active Parietal Cell 1. Blair JA, et al. J Clin Invest. 1987;79:582-587. 2. Sachs G. Pharmacotherapy. 1997;17:22-37. 1. Del Valle J, et al. Acid peptic disorders. In: Yamada et al, eds. Textbook of Gastroenterology.4th ed. Philadelphia, Pa: Lippincott Williams and Wilkins; 2003:1321-1376.

6. Proton Pump Inhibitors PPI PPI PPI PPI H+ H+ Acid is required to convert a PPI into its active form1 PPIs only bind to active proton pumps1 Unstimulated proton pumps remain 1. Del Valle J, et al. Acid peptic disorders. In: Yamada et al, eds. Textbook of Gastroenterology.4th ed. Philadelphia, Pa: Lippincott Williams and Wilkins; 2003:1321-1376.

7. Ensures that maximum plasma concentration of PPI coincides with the activation of proton pumps Results of a recent survey: Optimal Timing of PPI Dose More than one-third of all primary care physicians fail to educate patients properly on the timing of PPI dosing Chey Am J Gastroenterol 2005;100:1237.

8. Overuse of PPI Heidelbaugh et al. Am J Gastro 2006; 101: 2200-2205 Glew et al. J Am Med Dir Assoc 2007; 9:280-281 Choudhry et al. QJM 2008; 101:445-448. Bajaj et al. Am J Gastro, 2009; 104: 1130-1134. Retrospective, chart review of non-ICU admits1 • 22% received stress ulcer prophylaxis • 54% of those were discharged home on it Retrospective chart review of nursing home admits2 • 50% did NOT have an appropriate diagnosis for PPI Retrospective chart review of C.diff positive patients3 • 63% of did NOT have valid indication for PPI Retrospective chart review of cirrhotics + SBP4 • 47% did NOT have valid reason for PPI

9. Stopping a PPI: Rebound Acid • High Gastrin Levels • Rebound Acid • Step down therapy? • Warn patients of symptoms • Advise PRN H2 blocker therapy Reimer et al. Gastro 2009; 137: 80-87 Niklasson et al. Am J Gastro 2010; 105: 1531-1537.

10. PPI interaction with Clopidogrel 1. Khalique et al. Cardiology in Review 2009; 17: 198-200 2. Gilard, et al. J Am Coll Cardiol2008; 51: 256–260 3. Sibbing et al. Thromb Haemost 2009; 101: 714-719 4. O’Donaghue et al. Lancet 2009; 374:989-997 Clopidogrel is a prodrug that is converted to an active metabolite which irreversibly binds to the platelet P2Y12 receptor, blocking activation and aggregation Active metabolite formed via cytochrome P450 system Certain PPIs inhibit the cytochrome P450 2C19 pathway and may interfere with conversion of clopidogrel to the active form2-4 Newer studies question this finding? Pantoprazole studied and no increased risk

11. Case #2 – Chronic Diarrhea – C. Diff 72F with recurrent chronic diarrhea after hospitalization - diagnosed with C. diff Placed on Metronidazole then oral Vancomycin 10-15 bowel movements per day after completing therapy Repeat Metronidazole course Prolonged course of oral Vancomycin Consider Fecal Transplant Add probiotics to oral Vancomycin

12. Clostridium Difficile Increasing Rates

13. NAP1 Virulent Strain of C. Diff Pepin, J, Mortality attributable to nosocomial Clostridium difficile-associated disease during an epidemic caused by a hypervirulent strain in Quebec. CMAJ 2005; 173: 1–6. Hypervirulent strain: • NAP1/BI/027 • First report in N. America 2002: 30 Quebec hospitals • 30 day mortality of 23% compared to matched controls (Pepin) • Universally resistant to fluoroquinolones (selective advantage) (Gould. Bench to bedside review, Critical Care 2009) Number of discharges diagnosed with C diff. doubled from 2001 – 2005 Length of stay in association with C diff. is 3x average & mortality 4.5x average

14. Fecal Transplant for C. Diff

15. UVA Medical Center FMT Program • Call 434-924-2959 • Currently evaluating and treating limited numbers of patients for FMT • FMT via colonoscopy • Rule out predisposing conditions • Full scale program begins 9/1/2013

16. Case #3 – Appropriate Diet? 45F with HCV cirrhosis with asterixis Admitted to the hospital for fever work up History of severe encephalopathy and SBP What diet is appropriate for this admission? A. Low fat diet B. Low sodium diet C. Low protein diet D. Low taste diet

17. Nutritional Management Merli & Riggio, Metabolic Brain Disease, Dec 2008.

18. Nutritional Management Cirrhosis depletes body mass – catabolic state Liver unable to derive glucose Decreased ability for gluconeogenesis Glucose thus derived from muscle and adipose catabolism Increases protein requirements

19. Ammonia Level in PSE Nicolao et al., 2003 • 17 patients followed with PSE resolved • Ammonia levels did NOT decrease • Some levels increased with PSE resolution Conclusion • Ammonia levels of limited use for diagnosis or clinical management Nicolao et al., Journal of Hepatology, 2003, 38, 441-446.

20. Ammonia Level in PSE Kundra et al., 2005 • Evaluated 20 patients with CLD • Stage II mean ammonia level - 72.3 • Stage III mean ammonia level - 58.7 • Stage IV mean ammonia level - 42.0 Kundra et al.,Clinical Biochemistry, 2005, 38, 696-699.

21. Ammonia Level - Utility? No utility in diagnosis of PSE Ammonia levels may give provider false security or worry Assess asterixis, objective functioning “Only confusion an ammonia level measures is the confusion of the provider ordering the test.”

22. Case #4 – Groin Pain • 56M significant alcohol use – cirrhosis • 3rd and 4th degree burns in groin and scrotum • Burning off frayed edges of jean shorts “jhorts” • Admitted for 3-4 days at time of consult • Pain medications for dressing changes? • Acetaminophen • Ibuprofen • Morphine • Tramadol

23. Pain Medication in Cirrhosis • Issues with clearance • Altered metabolism • 3 modes of metabolism, often hindered: • P450 Pathway • Conjugation • Biliary Excretion • Tylenol - up to 2g per day?

24. NSAIDs in Cirrhosis • NSAIDs heavily protein bound • Elevated levels in cirrhosis • Renal Impairment - decreased perfusion • Increased bleeding risk with thrombocytopenia

25. Opioids in Cirrhosis Chandock, Watt, Mayo Clinic Proceedings, 2010, 85(5), 451-8.

26. Preferred Opioids in Cirrhosis? • Tramadol • Works on peripheral pain • Low affinity for opiod receptors • Less sedation effect • Lower potential for tolerance • Fentanyl IV or Hydromorphone PO • Least affected by renal function • Order in lower doses and longer intervals

27. Pain Medication Algorithm Start with Acetaminophen Try Tramadol Use opiates for intractable pain Chandock, Watt, Mayo Clinic Proceedings, 2010, 85(5), 451-8.

28. Clinical Pearls Proton Pump Inhibitors • Dose 30 min before meals • Stopping therapy may cause rebound symptoms Refractory C. Diff • Consider Fecal Transplant

29. Clinical Pearls • Hepatic Encephalopathy • Ammonia level of limited use • Low protein diets can harm patient • Pain Medication • Attempt Tylenol in limited doses • Next would attempt Tramadol • Consider Fentanyl or Hydromorphone in lower doses, less frequency

30. Thank you for your attention