neeral l. shah, m.d., f.a.c.p assistant professor of medicine division of gastroenterology and...
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Neeral L. Shah, M.D., F.A.C.P
Assistant Professor of Medicine
Division of Gastroenterology and Hepatology
Transplant Clinic Director
GI Clinical Pearls
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Clinical Pearls
■ Upper GI DiseasesPPI Therapy
■ Lower GI DiseasesColon - C. diff
■ HepatologyAmmonia LevelsPain Management
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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
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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)
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Proton Pump Functioning
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.
Unstimulated proton pumpsActive proton pumps
Unstimulated proton pumpsin cytoplasmic tubules
1. Blair JA, et al. J Clin Invest. 1987;79:582-587.2. Sachs G. Pharmacotherapy. 1997;17:22-37.
Gastrin
H2
ACh
H2 = Histamine
ACh = Acetylcholine
Proton pumps become activated in response to food1
Inactive Parietal Cell
After activation, the parietal cell undergoes a series of changes,allowing proton pumps to reach the surface of the parietal cell1
Active Parietal Cell
Only active proton pumps can secrete acid1However, not all pumps become activated1,2
ATPase
ATPase
H+
H+
H+
H+
K+
K+
K+
K+
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Proton Pump Inhibitors
Acid is required to convert a PPI into its active form1
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.
PPIs only bind to active proton pumps1
Unstimulated proton pumps remain
PPI
PPI PPI
PPI
H+
H+
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Optimal Timing of PPI Dose
■ Ensures that maximum plasma concentration of PPI coincides with the activation of proton pumps
Results of a recent survey:
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.
DOSING: ADMINISTER PPI:
QD 30 minutes before breakfast
BID 30 minutes before breakfast & evening meal
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Overuse of PPI
1. Heidelbaugh et al. Am J Gastro 2006; 101: 2200-22052. Glew et al. J Am Med Dir Assoc 2007; 9:280-2813. Choudhry et al. QJM 2008; 101:445-448.4. 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
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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: 80-87Niklasson et al. Am J Gastro 2010; 105: 1531-1537.
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PPI interaction with Clopidogrel
1. Khalique et al. Cardiology in Review 2009; 17: 198-200 2. Gilard, et al. J Am Coll Cardiol 2008; 51: 256–2603. Sibbing et al. Thromb Haemost 2009; 101: 714-7194. 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
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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
A.Repeat Metronidazole course
B.Prolonged course of oral Vancomycin
C.Consider Fecal Transplant
D.Add probiotics to oral Vancomycin
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Clostridium Difficile Increasing Rates
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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
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Fecal Transplant for C. Diff
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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
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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 dietB. Low sodium dietC. Low protein dietD. Low taste diet
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Nutritional Management
Merli & Riggio, Metabolic Brain Disease, Dec 2008.
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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
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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.
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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.
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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.”
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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?
A. AcetaminophenB. IbuprofenC. MorphineD. Tramadol
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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?
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NSAIDs in Cirrhosis
■ NSAIDs heavily protein bound
■ Elevated levels in cirrhosis
■ Renal Impairment - decreased perfusion
■ Increased bleeding risk with thrombocytopenia
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Opioids in Cirrhosis
Chandock, Watt, Mayo Clinic Proceedings, 2010, 85(5), 451-8.
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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
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Pain Medication Algorithm
Chandock, Watt, Mayo Clinic Proceedings, 2010, 85(5), 451-8.
Start with Acetaminophen
Try Tramadol
Use opiates for intractable pain
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Clinical Pearls
■ Proton Pump Inhibitors■ Dose 30 min before meals■ Stopping therapy may cause rebound symptoms
■ Refractory C. Diff■ Consider Fecal Transplant
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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
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Thank you for your attention