Transcript Stopping a PPI

GI Clinical Pearls
Neeral L. Shah, M.D., F.A.C.P
Assistant Professor of Medicine
Division of Gastroenterology and Hepatology
Transplant Clinic Director
Clinical Pearls
■ Upper GI Diseases
 PPI
Therapy
■ Lower GI Diseases
 Colon
- C. diff
■ Hepatology
 Ammonia
Levels
 Pain Management
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
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)
Proton Pump Functioning
1
1food
After Proton
activation,
thenot
parietal
cell
undergoes
a series
of
changes,
pumps
become
activated
in secrete
response
to1,2
Only
active
proton
pumps
can
acid
However,
all pumps
become
activated
allowing proton pumps to reach the surface of the parietal cell1
H2
K+
H+
K+
H+
ACh
K+
H+
Unstimulated
proton pumps
Active
Unstimulated
in cytoplasmic
proton
pumps
tubules
K+
H+
H2 = Histamine
ACh = Acetylcholine
Gastrin
Inactive
ParietalCell
Cell
Active Parietal
1.
1.Blair
Del Valle
JA, etJ,al.
et Jal.Clin
Acid
Invest.
peptic1987;79:582-587.
disorders. In: Yamada et al, eds. Textbook of Gastroenterology.
2. Sachs
4th ed.
G.Philadelphia,
Pharmacotherapy.
Pa: Lippincott
1997;17:22-37.
Williams and Wilkins; 2003:1321-1376.
Proton Pump Inhibitors
1 form1
Acid isPPIs
required
convert
a PPI
into its
active
only to
bind
to active
proton
pumps
H+
Unstimulated
proton pumps
remain
PPI
H+
PPI
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.
Optimal Timing of PPI Dose
DOSING:
ADMINISTER PPI:
QD
30 minutes before breakfast
BID
30 minutes before breakfast & evening meal
■ 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.
Overuse of PPI
■ 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
1.
2.
3.
4.
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.
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.
PPI interaction with Clopidogrel
■ 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
1. Khalique et al. Cardiology in Review 2009; 17: 198-200
2. Gilard, et al. J Am Coll Cardiol 2008; 51: 256–260
3. Sibbing et al. Thromb Haemost 2009; 101: 714-719
4. O’Donaghue et al. Lancet 2009; 374:989-997
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
Clostridium Difficile Increasing Rates
NAP1 Virulent Strain of C. Diff
■ 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
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.
Fecal Transplant for C. Diff
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
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
Nutritional Management
Merli & Riggio, Metabolic Brain Disease, Dec 2008.
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
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.
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.
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.”
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. Acetaminophen
B. Ibuprofen
C. Morphine
D. Tramadol
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?
NSAIDs in Cirrhosis
■ NSAIDs heavily protein bound
■ Elevated levels in cirrhosis
■ Renal Impairment - decreased perfusion
■ Increased bleeding risk with thrombocytopenia
Opioids in Cirrhosis
Chandock, Watt, Mayo Clinic Proceedings, 2010, 85(5), 451-8.
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
Pain Medication Algorithm
Start with
Acetaminophen
Try Tramadol
Use opiates for
intractable pain
Chandock, Watt, Mayo Clinic Proceedings, 2010, 85(5), 451-8.
Clinical Pearls
■ Proton Pump Inhibitors
■ Dose 30 min before meals
■ Stopping therapy may cause rebound symptoms
■ Refractory C. Diff
■ Consider Fecal Transplant
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
Thank you for your attention