Gastrointestinal Disorders Medicine Didactics Lecture

Gastrointestinal
Disorders
Grace Carpenter, PharmD
PGY1 Acute Care Pharmacy Resident
Objectives
1. Review diagnostic strategies for numerous
gastrointestinal (GI) disorders.
2. Evaluate various treatment options for each GI
disorder.
3. Create therapeutic recommendations using a
number of guidelines and primary literature.
Table of Contents
01 Intra-abdominal Infections
02 Liver Disease & Complications
03 Nausea & Vomiting

01
Intra-abdominal
Infections
Initial Patient Evaluation
1. Is the infection community or hospital-acquired?
a. Blood cultures are not routinely recommended for
community-acquired infections
2. Does the patient have risk factors for resistant
organisms?
a. Gram stains and cultures are considered optional in low risk
community-acquired infections unless there is high rate of E. coli
resistance (10-20%) to a commonly used regimen
3. Does the patient have immunocompromising
conditions?
Solomkin JS, Mazuski JE, Bradley JS, et al. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines
by The Surgical Infection Society and The Infectious Diseases Society of America. Clin Infect Dis. 2010;50(2):133-164. doi:10.1086/649554
What is one of the most
important parts of managing GI
infections?
What is one of the most
SOURCE
important CONTROL
parts of managing!GI
infections?
Typical Antibiotic Coverage
- Enteric facultative aerobic Gram-negative rods
- Enteric Gram-positive streptococci
- Obligate anaerobic bacilli
Mazuski JE, Tessier JM, May AK, et al. The Surgical Infection Society revised guidelines on the management of intra-abdominal infection. Surg
Infect. 2017;18(1). doi:10.1089/sur.2016.261
Antibiotic Coverage
Facultative & Aerobic Gram-Negative Rods
- Escherichia coli, Klebsiella spp., Pseudomonas aeruginosa,
Proteus mirabilis, Enterobacter spp.
Gram-Positive Aerobic Organisms

- Streptococcus spp., Enterococcus spp., S. aureus
Anaerobic Organisms (most common in infections of the small

bowel, appendix, or colon or in the presence of any GI perforation)
- Bacteroides spp., Clostridium spp., Peptostreptococcus spp.,
Fusobacterium spp., etc.
Antibiotic Choice
1. Recommended that ampicillin-sulbactam (Unasyn) is
not routinely used (66% susceptible to E. coli at SJHS).
2. Recommended that anti-pseudomonal regimens are
not used in low risk community-acquired infections.
3. Do not utilize clindamycin for anaerobic coverage if at
all possible.
Infect. 2017;18(1). doi:10.1089/sur.2016.261
Antibiotic Choice
1. Recommended that ampicillin-sulbactam (Unasyn) is
not routinely used (66% susceptible to E. coli at SJHS).
2. Recommended that anti-pseudomonal regimens are
not used in low risk community-acquired infections.
3. Do not utilize clindamycin for anaerobic coverage if at
all possible.
Infect. 2017;18(1). doi:10.1089/sur.2016.261
Antibiotic Choice
1. Low Risk: Ceftriaxone + metronidazole OR ciprofloxacin +
metronidazole if cephalosporin allergy is present (see next
slide)
2. High Risk: Ceftazidime/cefepime + metronidazole OR
piperacillin-tazobactam
3. Oral Antibiotics:
a. Amoxicillin-Clavulanate
b. Ciprofloxacin + metronidazole (if allergy present)
Infect. 2017;18(1). doi:10.1089/sur.2016.261
SJHS Allergy
Chart
Antibiotic Duration
1. Limit to 4 days if patient has achieved adequate
source control.
2. Limit to 5-7 days if patient has not had source
control.
a. Utilize inflammatory markers to guide
antibiotic discontinuation.
3. Limit to 7 days if patient has a secondary
bacteremia and has had adequate source
control.
Mazuski JE, Tessier JM, May AK, et al. The Surgical Infection Society revised guidelines on the
management of intra-abdominal infection. Surg Infect. 2017;18(1). doi:10.1089/sur.2016.261
Role of Antifungal Therapy
1. Hospital-acquired GI infections secondary to bowel
perforations
2. Patients on long-term broad-spectrum antibiotics
3. Patients known to be heavily colonized with Candida
Use an echinocandin for severely ill patients at high risk or
patients with fluconazole-resistant Candida
Use fluconazole for mild-moderately ill patients at high risk
Mazuski JE, Tessier JM, May AK, et al. The Surgical Infection Society revised guidelines on the
management of intra-abdominal infection. Surg Infect. 2017;18(1). doi:10.1089/sur.2016.261
C. difficile Diagnosis
- Ensure to test all patients with suspicion for C. difficile on
admission - do not wait!
- We utilize the C. difficile nucleic acid amplification test (aka
toxin gene NAAT) with reflex to the toxin A and B enzyme
immunoassay test (EIA)
- The NAAT has high sensitivity + low/moderate specificity
- Toxin A and B test has low sensitivity + moderate specificity
- If only the NAAT is positive but the patient has symptoms, okay
to treat
Johnson S, Laverne V, Skinner AM, et al. Clinical practice guideline by the Infectious Diseases Society of America (IDSA)
and Society for Healthcare Epidemiology of America (SHEA): 2021 focused update guidelines on management of
Clostridioides difficile infection in adults. Clin Infect Dis. 2021. 10.1093/cid/ciab549
IDSA C. difficile Guidelines
Initial Episode: Fidaxomicin (Dificid) 200 mg PO BID x 10 days*^
Recurrent CDI Episodes: Same recommendation as above*✝^
Fulminant Disease: Vancomycin 500 mg PO QID x 14 days*^

PLUS metronidazole 500 mg IV q8h
*Vancomycin 125 mg PO QID x 10 days is an alternative option

✝
Pulsed/tapered regimens are considered acceptable alternatives
^
Rectal vancomycin can be used for patients who are unable to take PO
Johnson S, Laverne V, Skinner AM, et al. Clinical practice guideline by the Infectious Diseases Society of America (IDSA)
and Society for Healthcare Epidemiology of America (SHEA): 2021 focused update guidelines on management of
Clostridioides difficile infection in adults. Clin Infect Dis. 2021. 10.1093/cid/ciab549
C. difficile : Vancomycin vs Flagyl
Patient Population: 150 patients (81 patients had mild disease
and 69 had severe disease)
Mild Disease Cure Severe Disease

Overall Rate of Cure
Rate Cure Rate
Vancomycin
97% 98% 97%
(71 pts)
Metronidazole
84 % 90% 76%
(79 pts)
Significance p = 0.006 p = 0.36 p = 0.02

Zar FA, Bakkanagari SR, Moorthi KMLST, et al. A comparison of vancomycin and metronidazole for the treatment of C.
difficle-associated diarrhea, stratified by disease severity. Clin Infect Dis. 2007;45(3):302-7. doi:10.1086/519265
SJHS C. difficile Treatment
At SJHS, fidaxomicin is recommended in
high-risk patients such as:
1. Age > 65 years of age
2. Immunocompromised
3. Severe C. difficile infection
4. Patients requiring concomitant
antibiotics
5. Multiple recurrences
*Laura Gillespie, our ID pharmacist, collected one

year of C. difficile patient data and there were no
cases of recurrence with PO vancomycin.
C. difficile Adjunct Therapy
Bezlotoxumab (Zinplava): For patients on C. difficile
treatment to help prevent recurrence
- Mechanism: Binds to C. difficile toxin B to neutralize its effects
- Usually an outpatient medication, but there are strict inpatient
criteria for use.
- Avoid in patients with history of heart failure
Johnson S, Laverne V, Skinner AM, et al. Clinical practice guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 focused
update guidelines on management of Clostridioides difficile infection in adults. Clin Infect Dis. 2021. 10.1093/cid/ciab549
Bezlotoxumab. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL. Accessed March 19, 2024. http://online.lexi.com
C. difficile Adjunct Therapy
- Fecal microbiota transplant (FMT)
- Rebyota: An FDA-approved, single-dose rectal FMT
- Vowst: An FDA-approved, PO FMT
Fecal Microbiota (Live) (Rectal). Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc.
Riverwoods, IL. Accessed March 19, 2024. http://online.lexi.com
Johnson S, Laverne V, Skinner AM, et al. Clinical practice guideline by the Infectious Diseases Society of America (IDSA) and Society for
Healthcare Epidemiology of America (SHEA): 2021 focused update guidelines on management of Clostridioides difficile infection in adults. Clin Fecal Microbiota (Live) (Oral). Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc.
Infect Dis. 2021. 10.1093/cid/ciab549 Riverwoods, IL. Accessed March 19, 2024. http://online.lexi.com
Antibiotics Causing C. difficile
Clindamycin is
the biggest
offender!
Zhang J, Chen L, Gomez-Simmonds A, et al.

Antibiotic-specific risk for community-acquired
Clostroides difficile infection in the United States from
2008 to 2020. Antimicrob Agents Chemother.
2022;66(12):e01129-22. doi:10.1128/aac.01129-22
02
Liver Disease &
Complications
Nonalcoholic Fatty Liver Disease (NAFLD)
Definition: Consumption of little to no alcohol with ≥ 5% of
hepatocytes demonstrating macrovesicular steatosis and no
other causes easily identified (medications, starvation, etc.)
Potentially Causative Medications: Amiodarone, fluorouracil
(5-FU), irinotecan, tamoxifen, methotrexate, steroids
Rinella ME, Neuschwander-Tetri BA, Siddiqui MS, et al. AASLD practice guidance on the clinical assessment and management of nonalcoholic fatty liver
disease. Hepatology. 2023;77(5):1797-1835. doi:10.1097/HEP.0000000000000323
Nonalcoholic Steatohepatitis (NASH)
Definition: Diagnosis of NAFLD along with presence of
inflammation and cellular injury
Rinella ME, Neuschwander-Tetri BA, Siddiqui MS, et al. AASLD practice guidance on
the clinical assessment and management of nonalcoholic fatty liver disease.
Hepatology. 2023;77(5):1797-1835. doi:10.1097/HEP.0000000000000323
Fibrosis-4 (FIB-4) for Fibrosis Scoring
FIB-4 Score = (Age x AST) / [Platelets x √(ALT)]
Rinella ME, Neuschwander-Tetri BA, Siddiqui MS, et al. AASLD practice guidance on the clinical assessment and management Fibrosis-4 (FIB-4) Index for Liver Fibrosis. MdCalc. Accessed March 25, 2024.
of nonalcoholic fatty liver disease. Hepatology. 2023;77(5):1797-1835. doi:10.1097/HEP.0000000000000323 https://www.mdcalc.com/calc/2200/fibrosis-4-fib-4-index-liver-fibrosis
Rinella ME, Neuschwander-Tetri BA, Siddiqui MS, et al. AASLD
practice guidance on the clinical assessment and management of
nonalcoholic fatty liver disease. Hepatology. 2023;77(5):1797-1835.
doi:10.1097/HEP.0000000000000323
NAFLD/NASH Treatment
- Healthy diet and weight loss
- Pharmacologic Treatment (none are FDA-approved)
- Vitamin E 800 units PO QD
- Pioglitazone 30 mg PO QD x 2 months, then increase to 45 mg
PO QD (with or without diabetes)
- GLP-1 Receptor Antagonists
- Effect of SGLT2 inhibitors needs to be studied further
Rinella ME, Neuschwander-Tetri BA, Siddiqui MS, et al. AASLD practice guidance on
the clinical assessment and management of nonalcoholic fatty liver disease.
Hepatology. 2023;77(5):1797-1835. doi:10.1097/HEP.0000000000000323
Diagnosing Cirrhosis
Suspicion: Hepatomegaly, elevations in AST/ALT/INR/bilirubin,
low platelet count or albumin, physical findings, etc.
Diagnosis: Liver biopsy is gold standard but invasive. A
combination of lab testing, imaging, and medical history can be
used instead.
Smith A, Baumgartner K, Bositis C. Cirrhosis: diagnosis and management. Am Fam

Physician. 2019;100(12):759-770.
Complications of Cirrhosis
Biggins SW, Angeli P, Garcia-Tsao G, et al.

Diagnosis, evaluation, and management of
ascites, spontaneous bacterial peritonitis, and
hepatorenal syndrome: 2021 practice guidance
by the American Association for the Study of
Liver Diseases. Hepatology.
2021;74(2):1014-1048.
doi:10.0002/hep.31884
Child-Pugh Score
Score 1 2 3
Severe or
Ascites None Mild-moderate
intractable
Encephalopathy None Grade 1 or 2 Grade 3 or 4
Bilirubin (μmol/L) < 35 35-50 > 50
Albumin (g/L) > 35 28-35 < 28
INR ≤ 1.7 1.71-2.3 > 2.3
Indicates severity of cirrhosis: Child-Pugh A: 5-6 points

Child-Pugh B: 7-9 points
Child-Pugh C: 10-15 points
Gentile JA, Boone LB, Kyle JA, et al. Drug considerations for medication therapy in
cirrhosis. US Pharm. 2020;45(12):9-12.
MELD Score
MELD-Na (UNOS/OPTN). MdCalc. Accessed March 22, 2024.

https://www.mdcalc.com/calc/78/meld-score-model-end-stag
e-liver-disease-12-older
Portal Hypertension
Definition: Difference in portal and hepatic venous pressure of ≥ 5 mmHg
Diagnosis: Ultrasound, CT, or MRI demonstrating portocollateral
circulation
Kaplan DE, Ripoll C, Thiele M, et al. AASLD practice guidance on risk stratification Garcia-Tsao G, Abraldes JG, Berzigotti A, et al. Portal hypertensive bleeding in cirrhosis: risk stratification,
and management of portal hypertension and varices in cirrhosis. Hepatology. 2023. diagnosis, and management: 2016 practice guidance by the American Association for the study of liver
doi:10.1097/HEP.0000000000000647 diseases. Hepatology. 2017;65(1):310-335. doi:10.1002/hep.28906
Portal Hypertension & Varices
Non-Selective Beta Blockers (NSBBs)
- Mechanism: Decreases portal blood flow through ↓ cardiac
output and ↓ splanchnic vasoconstriction
- Carvedilol is preferred (start at 6.25 mg/day)
- Does not require heart rate-based titration
- Decreases hepatic venous pressure gradient (HVPG) more
than other NSBBs (i.e., propranolol or nadolol)
- Continue indefinitely
Garcia-Tsao G, Abraldes JG, Berzigotti A, et al. Portal hypertensive bleeding in cirrhosis: risk stratification,
diagnosis, and management: 2016 practice guidance by the American Association for the study of liver
diseases. Hepatology. 2017;65(1):310-335. doi:10.1002/hep.28906
Variceal Hemorrhage
Medication Mechanisms
Somatostatin: A hormone that inhibits vasodilator hormone
release leading to splanchnic vasoconstriction and decreased
portal blood flow
- Octreotide (Sandostatin ®) is a somatostatin analog
- Preferred option
Vasopressin: Directly constricts mesenteric arteries reducing

portal inflow
- Terlipressin is a vasopressin analog (not available in U.S.)
Ocreotide. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL. Accessed March 25, 2024. http://online.lexi.com
Vasopressin. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL. Accessed March 25, 2024. http://online.lexi.com
Variceal Hemorrhage
1. Perform EGD and complete endoscopic variceal ligation
(EVL) if a source is detected
2. Give packed red blood cells to ensure hemoglobin remains ≥
7 g/L
3. Start prophylactic ceftriaxone for a maximum of 7 days until
hemorrhage is resolved
4. For patients at high risk for bleeding recurrence, may
consider transjugular intrahepatic portosystemic shunt (TIPS)
Ascites
Most common initial decompensation event
(5-10% of patients with compensated
cirrhosis per year will develop).
Diagnosis: Calculation of serum albumin ascites gradient ≥ 1.1

g/dL (97% specificity)
Biggins SW, Angeli P, Garcia-Tsao G, et al. Diagnosis, evaluation, and management of ascites, spontaneous bacterial
peritonitis, and hepatorenal syndrome: 2021 practice guidance by the American Association for the Study of Liver
Diseases. Hepatology. 2021;74(2):1014-1048. doi:10.0002/hep.31884
Treatment of Ascites
Sodium restriction → maximum of 2 grams/day
a. A 24-hour urinary sodium excretion test can demonstrate an
insufficient diuretic dose if urine sodium is less than sodium
intake
Diuretics: Spironolactone 100 mg QD + furosemide 40 mg QD
a. Full effect of spironolactone is not seen until 3 days post-dose
b. Pts with chronic kidney disease should get higher doses of
furosemide and lower of spironolactone
Grade 3 Ascites: Large volume paracentesis combined with albumin
Biggins SW, Angeli P, Garcia-Tsao G, et al. Diagnosis, evaluation, and management of ascites, spontaneous bacterial peritonitis,
and hepatorenal syndrome: 2021 practice guidance by the American Association for the Study of Liver Diseases. Hepatology.
2021;74(2):1014-1048. doi:10.0002/hep.31884
Hepatic Encephalopathy (HE)
- Elevated ammonia levels alone do not add West Haven Criteria
diagnostic, prognostic, or staging value
- Repeat ammonia levels can be beneficial
to test efficacy of ammonia-lowering
medications
- Primary Prophylaxis: Not recommended
- Secondary Prophylaxis: Recommended
Vilstrup H, Amodio P, Bajaj J, et al. Hepatic encephalopathy in chronic liver disease: 2014 practice
Hepatic Encephalopathy Grades/Stages. MdCalc. Accessed March 24, 2024.
guideline by the American Association for the Study of Liver Diseases and the European Association for
https://www.mdcalc.com/calc/674/hepatic-encephalopathy-grades-stages
the Study of the Liver. Hepatology. 2014;60(2):715-735. doi:10.1002/hep.27210
HE Treatment
Lactulose 20-30 g PO titrated to 2-3 bowel movements per day
- Mechanism:
Rifaximin 550 mg PO BID or 400 mg PO TID

- Mechanism: Prevents bacterial RNA synthesis
Lactulose. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL.
Accessed March 24, 2024. http://online.lexi.com
Vilstrup H, Amodio P, Bajaj J, et al. Hepatic encephalopathy in chronic liver disease: 2014 practice
guideline by the American Association for the Study of Liver Diseases and the European Association for Rifaximin. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL.
the Study of the Liver. Hepatology. 2014;60(2):715-735. doi:10.1002/hep.27210 Accessed March 24, 2024. http://online.lexi.com
Hepatorenal Syndrome (HRS)
Definition: Acute kidney injury (AKI) in the setting of cirrhosis
but in the absence of hypovolemia, structural kidney damage,
and nephrotoxic medications
- 30-day mortality of up to 44% in patients with HRS
Arterial vasodilation
secondary to portal Arterial underfilling
hypertension
Vasoconstriction and renal

hypoperfusion
Biggins SW, Angeli P, Garcia-Tsao G, et al. Diagnosis, evaluation, and management of ascites, spontaneous bacterial
peritonitis, and hepatorenal syndrome: 2021 practice guidance by the American Association for the Study of Liver Diseases.
Hepatology. 2021;74(2):1014-1048. doi:10.0002/hep.31884
Treatment of HRS
ICU Patients: Norepinephrine + albumin
Non-ICU Patients: Midodrine, ocreotide (SQ or IV), and

albumin
- Much lower efficacy than above regimen
Renal replacement therapy may be necessary
Duration: Treat for 2 weeks or until patients renal function is

back to baseline
Biggins SW, Angeli P, Garcia-Tsao G, et al. Diagnosis, evaluation, and management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome:
2021 practice guidance by the American Association for the Study of Liver Diseases. Hepatology. 2021;74(2):1014-1048. doi:10.0002/hep.31884
Spontaneous Bacterial Peritonitis (SBP)
Definition: Ascitic fluid infection without a source
Cause: Bacterial translocation and reduced host defenses
Suspicion of SBP: Patients with cirrhosis who develop ascites,
abdominal pain, AKI, jaundice, and/or encephalopathy
- Up to one third of patients may be asymptomatic
Diagnosis: Diagnostic paracentesis
(polymorphonuclear neutrophils (PMNs) > 250/mm3)
- Positive ascitic fluid culture is still important!
Biggins SW, Angeli P, Garcia-Tsao G, et al. Diagnosis, evaluation, and management of ascites, spontaneous bacterial peritonitis, and hepatorenal
syndrome: 2021 practice guidance by the American Association for the Study of Liver Diseases. Hepatology. 2021;74(2):1014-1048.
doi:10.0002/hep.31884
Treatment of SBP
Possible Organisms: Sixty percent of organisms growing are
Gram-negative
- Frequent: E. coli, K. pneumoniae
- Infrequent: S. aureus, Enterococcus spp.
- Positive cultures are typically monobacterial
Prophylaxis: Ceftriaxone 1 g IV QD
- Prior episode, variceal hemorrhage, low ascitic fluid protein (< 1.5
g/dL)
Treatment: Ceftriaxone 1 g IV QD x 5-7 days

Biggins SW, Angeli P, Garcia-Tsao G, et al. Diagnosis, evaluation, and
management of ascites, spontaneous bacterial peritonitis, and hepatorenal
syndrome: 2021 practice guidance by the American Association for the Study of
Liver Diseases. Hepatology. 2021;74(2):1014-1048. doi:10.0002/hep.31884
Treatment of SBP
Gram-negative
Which of the possible organisms are
not
Prophylaxis: covered
Ceftriaxone by
1 g IV QD ceftriaxone?
g/dL)

Treatment of SBP
Gram-negative
Which of the possible organisms are
not covered by ceftriaxone?
Prophylaxis: Ceftriaxone 1 g IV QD
g/dL) Enterococcus and S. aureus!
Medications & Liver Disease
Statins: Prefer statins that are less extensively metabolized by
CYP 450, such as rosuvastatin or pravastatin
GERD Agents: Prefer famotidine and esomeprazole (must dose

No evidence-based guidelines exist
adjust other proton pump inhibitors)
for Puts
Metformin: hepatic
patients atdose adjustments
greater risk for lactic acidosis, avoid in
Child-Pugh Class C
- Still requires dose adjustment in Child-Pugh Class B
Gentile JA, Boone LB, Kyle JA, et al. Drug considerations for medication therapy in cirrhosis. US Pharm. 2020;45(12):9-12.
Statins: Prefer statins that are less extensively metabolized by
CYP 450, such as rosuvastatin or pravastatin
GERD Agents: Prefer famotidine and esomeprazole (must dose

adjust other proton pump inhibitors)
Metformin: Puts patients at greater risk for lactic acidosis, avoid in

Child-Pugh Class C
- Still requires dose adjustment in Child-Pugh Class B
- Macrolides: Azithromycin, clarithromycin, erythromycin
- Methotrexate
- mTOR Inhibitors (sirolimus, tacrolimus): Must be dose adjusted
and monitored
- Pioglitazone: Avoid in cirrhotic patients due to risk for edema
- ACEIs and ARBs: Avoid in presence of ascites secondary to
cirrhosis due to possible precipitation of HRS
- Ertapenem: Should not be used in hypoalbuminemia
Acetaminophen & Liver Dysfunction
Mechanism of Toxicity: Build up of acetaminophen’s toxic
metabolite, N-acetyl-p-benzoquinoneimine (NAPQI).
- 12-24 hours: Nausea, vomiting, and abdominal pain
- 24-72 hours: Slow rise in lab tests (INR, LFTs, bilirubin)
- 72-96 hours: LFTs peak and symptoms like jaundice,
encephalopathy, and coagulopathy may occur
Bond GR, Caravati EM, Dart RC, et al. Guidelines for the management of acetaminophen overdose. Accessed March 22, 2024.
https://www.tylenolprofessional.com/sites/tylenol_hcp_us/files/acetaminphen_overdose_treatment_info.pdf
Treatment of Acetaminophen Toxicity
Draw acetaminophen serum concentration 4 hours after
ingestion (or immediately if presenting later than 4 hours)
Within 4 hours of ingestion: Activated charcoal 1 g/kg x 1
N-Acetylcysteine (Acetadote ®)*

- Loading Dose: 150 mg/kg over 60 minutes
- Second Dose: 50 mg/kg over 4 hours
- Third Dose: 100 mg/kg over 16 hours
*For patients weighing > 100 kg, cap dosing weight at 100 kg.
Acetylcysteine. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL.
Hodgman MJ, Garrard AR. A review of acetaminophen poisoning. Crit Care Clin. 2012;28(4):499-516. doi:10.1016/j.ccc.2012.07.006
Treatment of Acetaminophen Toxicity
Draw acetaminophen serum concentration 4 hours after
ingestion (or immediately if presenting later than 4 hours)
Call Poison Control!
Within 4 hours of ingestion: Activated charcoal 1 g/kg x 1
Continue NAC
N-Acetylcysteine treatment
(Acetadote ®)* until APAP level is
<-- 10
Loading Dose: 150 mg/kg over 60 minutes
μg/mL and AST and ALT have peaked,
Second Dose: 50 mg/kg over 4 hours
- or otherwise
Third stated
Dose: 100 mg/kg byhours
over 16 Poison Control.
*For patients weighing > 100 kg, cap dosing weight at 100 kg.
Acetylcysteine. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL.
Hodgman MJ, Garrard AR. A review of acetaminophen poisoning. Crit Care Clin. 2012;28(4):499-516. doi:10.1016/j.ccc.2012.07.006
Rumack
Matthew
Nomogram
New Cirrhosis Treatment Study
Glal K, El-Haggar SM, Abdel-Salam SM, et al. Allopurinol prevents cirrhosis-related complications: a quadruple blind
placebo-controlled trial. Am J Med. 2023;137(1):55-64. doi:10.1016/j.amjmed.2023.09.016
Allopurinol Use in Cirrhosis
Study Population: 100 Egyptian patients
Inclusion:
- Diagnosed with hepatic decompensation (ascites, variceal
bleeding, HE, HRS, or SBP) and currently in remission
- 18-75 years of age
- Child-Pugh B or C with a MELD score of ≤ 25
Methods
- 50 patients received allopurinol 300 mg PO QD x 24 weeks
- 50 patients received placbeo
Allopurinol Use in Cirrhosis
Primary Endpoint (incidence of cirrhosis complications):
- 32% in allopurinol group and 72% in placebo group
- Relative risk reduction of 56% in first 6 months with
allopurinol treatment
Mechanism: Thought to be related to reduction in oxidative

stress caused by increased xanthine oxidase activity
03
Nausea &
Vomiting
Pathophysiology of Nausea & Vomiting
Heckroth M, Luckett RT, Moser C, et al. Nausea

and vomiting in 2021: a comprehensive update.
J Clin Gastroenterol. 2021;55(4):279-299.
doi:10.1097/MCG.0000000000001485
Dopamine Receptor Antagonists
Dopamine stimulates the chemotherapy trigger zone (CTZ)
Agents
- Metoclopromide (Reglan): Also promotes gastric motility
- Haloperidol (Haldol)
- Prochlorperazine (Compazine)
- Olanzapine: Also has activity at 5-HT2C and 5-HT3 receptors
Side Effects: Extrapyramidal symptoms, hypotension (Compazine),

QTc prolongation, neuroleptic malignant syndrome
Heckroth M, Luckett RT, Moser C, et al. Nausea and vomiting in 2021: a comprehensive update.
J Clin Gastroenterol. 2021;55(4):279-299. doi:10.1097/MCG.0000000000001485
Histamine Receptor Antagonists
Useful for motion sickness and pregnancy-associated N/V
Agents
- Promethazine (Phenergan) - also a weak dopamine antagonist
- Diphenhydramine (Benadryl)
- Dimenhydrinate (Dramamine)
- Doxylamine
- Meclizine
Side Effects: Dry mouth, urinary retention, sedation,
extrapyramidal symptoms, hypotension (promethazine)
Muscarinic Receptor Antagonists
Most often used for motion sickness
and in postoperative settings.
Agents
- Scopolamine (72-hour patch)
Side Effects: Dry mouth, urinary

retention, drowsiness
Serotonin Receptor Antagonists
Serotonin is released from enterochromaffin
cells when in contact with toxins or irritants,
sending stimuli to the emetic center
Agents
- Ondansetron (Zofran)
- Granisetron (Sancuso patch)
- Palonosetron (Aloxi) - not known to affect QTc
Side Effects: QTc prolongation, headache, constipation

Neurokinin-1 Receptor Antagonists
Beneficial in delayed nausea and vomiting where other agents
are not as useful.
Agents
- Aprepitant (Emend)
Side Effects: Hypotension, neutropenia, fatigue
Use timing to your advantage!
QTc Risk of Antiemetics
Clinically significant QTc:
- ≥ 500 msec
- ≥ 25% increase from baseline
- Change of ≥ 60 msec
^
Ondansetron 4 mg IV x 1
increased QTc by ~ 16 msec
Gueta I, Klempfner R, Markovitgs N, et al. Clinically significant incidental QTc prolongation is subject to within-individual variability. Ann
Noninvasive Electrocardiol. 2020;25(2):e12699. doi:10.1111/anec.12699
Hymel N, Davies M. Evidence-based antiemetic decision tool for management of postoperative nausea and vomiting in patients at high risk
of QT prolongation and patients receiving neurotransmitter-modulating medications. AANA J. 2020;88(4):312-318.
Hyperemesis Gravidarum
For refractory nausea and vomiting in pregnancy:
1. Methylprednisolone 16 mg q8h x 3 days
a. If beneficial, after 3 days taper over 2 weeks
b. Mechanism is unknown
2. Chlorpromazine IM/IV/PO
a. Patient should lay in supine position for 30 minutes
after administration to prevent orthostatic hypotension
b. Extrapyramidal symptoms are more common
Methylprednisolone. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL. Accessed March 25, 2024. http://online.lexi.com
Chlorpromazine. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL. Accessed March 25, 2024. http://online.lexi.com
Cyclic Vomiting Syndrome (CVS)
Diagnosis (Rome IV Criteria):
1. Acute onset of vomiting of < 1 week duration
2. ≥ 3 episodes in the prior year and 2 episodes in the past 6
months with 1 week or more between each episode
3. No vomiting between episodes (some mild symptoms may
be present)
Venkatesan T, Levinthal DJ, Tarbell SE, et al. Guidelines on management of cyclic vomiting
syndrome in adults by the American Neurogastroenterology and Motility Society and the Cyclic Rome IV Diagnostic Criteria for Cyclic Vomiting Syndrome. MdCalc. Accessed March 25, 2024.
Vomiting Syndrome Association. Neurogastroenterol and Motil. 2019;31. doi:10.1111/nmo.13604 https://www.mdcalc.com/calc/10299/rome-iv-diagnostic-criteria-cyclic-vomiting-syndrome
Cyclic Vomiting Syndrome (CVS)
Venkatesan T, Levinthal DJ, Tarbell SE, et al. Guidelines on management of cyclic vomiting syndrome in adults by the American Neurogastroenterology and Motility
Society and the Cyclic Vomiting Syndrome Association. Neurogastroenterol and Motil. 2019;31. doi:10.1111/nmo.13604
CVS Treatment
Prophylaxis (for moderate to severe CVS):
1. First-line: Amitriptyline 10-25 mg PO QHS (up to 100 mg/day)
a. Demonstrated reduction in incidence and duration of CVS
episodes as well as emergency department visits
2. Alternatives: Topiramate, aprepitant, zonisamide, levetiracetam,
Co-Q10, rivoflavin
Abortive Treatment:
1. Triptans, serotonin antagonists, aprepitant
2. Treat comorbid conditions (i.e., migraines, sleep disorders, etc.)
Venkatesan T, Levinthal DJ, Tarbell SE, et al. Guidelines on management of cyclic vomiting
syndrome in adults by the American Neurogastroenterology and Motility Society and the Cyclic
Vomiting Syndrome Association. Neurogastroenterol and Motil. 2019;31. doi:10.1111/nmo.13604
Cannabinoid Hyperemesis Syndrome (CHS)
Definition: Episodic, intractable vomiting associated with prolonged,
excessive cannabis use
- Typically relieved with hot showers or prolonged periods of
cannabis cessation
- Positive THC on drug test
Mechanism:
- Cannabis is a known antiemetic due to the ability of THC to
activate CB1 receptors which inhibits serotonin release
- Chronic cannabis use may cause downregulation or
desensitization of the CB1 receptor
Cannabinoid Hyperemesis Syndrome Clinical Pathway. Johns Hopkins All Children’s Hospital. Accessed March 25, 2024.
https://www.hopkinsmedicine.org/-/media/files/allchildrens/clinical-pathways/chs_pathway-5_19_23.pdf
Treatment of CHS
First-line antiemetic treatments (metoclopromide, ondansetron)
are usually ineffective
Specific dopamine antagonists are preferred based on several

studies
- Droperidol 0.625-1.5 mg
- At SJHS, this is restricted to the ED, OR, and
post-operative areas
- ECG monitoring is required for doses ≥ 2.5 mg
- Haloperidol 0.05-0.1 mg/kg (max of 2.5 mg)
Sabbineni M, Scott W, Punia K, et al. Dopamine antagonists and topical capsaicin for cannabinoid hypermesis syndrome in the emergency department: a systematic review of
direct evidence. Acad Emerg Med. 2023. doi:10.1111/acem.14770
Ruberto AJ, Sivilotti ML, Forrester S, et al. Intravenous haloperidol versus ondansertron for cannabinoid hyperemesis syndrome (HaVOC): a randomized, controlled trial. Ann Emerg
Med. 2021;77(6):613-619. doi:10.1016/j.annemergmed.2020.08.021
Thank you!
Questions?
References
1. Solomkin JS, Mazuski JE, Bradley JS, et al. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by
The Surgical Infection Society and The Infectious Diseases Society of America. Clin Infect Dis. 2010;50(2):133-164. doi:10.1086/649554
2. Mazuski JE, Tessier JM, May AK, et al. The Surgical Infection Society revised guidelines on the management of intra-abdominal infection. Surg Infect.
2017;18(1). doi:10.1089/sur.2016.261
3. Johnson S, Laverne V, Skinner AM, et al. Clinical practice guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare
Epidemiology of America (SHEA): 2021 focused update guidelines on management of Clostridioides difficile infection in adults. Clin Infect Dis. 2021.
10.1093/cid/ciab549
4. Bezlotoxumab. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL. Accessed March 19, 2024. http://online.lexi.com
5. Fecal Microbiota (Live) (Rectal). Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL. Accessed March 19, 2024. http://online.lexi.com
6. Fecal Microbiota (Live) (Oral). Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL. Accessed March 19, 2024. http://online.lexi.com
7. Zar FA, Bakkanagari SR, Moorthi KMLST, et al. A comparison of vancomycin and metronidazole for the treatment of C. difficle-associated diarrhea,
stratified by disease severity. Clin Infect Dis. 2007;45(3):302-7. doi:10.1086/519265
8. Zhang J, Chen L, Gomez-Simmonds A, et al. Antibiotic-specific risk for community-acquired Clostroides difficile infection in the United States from 2008
to 2020. Antimicrob Agents Chemother. 2022;66(12):e01129-22. doi:10.1128/aac.01129-22
9. Rinella ME, Neuschwander-Tetri BA, Siddiqui MS, et al. AASLD practice guidance on the clinical assessment and management of nonalcoholic fatty
liver disease. Hepatology. 2023;77(5):1797-1835. doi:10.1097/HEP.0000000000000323
10. Fibrosis-4 (FIB-4) Index for Liver Fibrosis. MdCalc. Accessed March 25, 2024. https://www.mdcalc.com/calc/2200/fibrosis-4-fib-4-index-liver-fibrosis
11. Smith A, Baumgartner K, Bositis C. Cirrhosis: diagnosis and management. Am Fam Physician. 2019;100(12):759-770.
12. Biggins SW, Angeli P, Garcia-Tsao G, et al. Diagnosis, evaluation, and management of ascites, spontaneous bacterial peritonitis, and hepatorenal
syndrome: 2021 practice guidance by the American Association for the Study of Liver Diseases. Hepatology. 2021;74(2):1014-1048.
doi:10.0002/hep.31884
13. Gentile JA, Boone LB, Kyle JA, et al. Drug considerations for medication therapy in cirrhosis. US Pharm. 2020;45(12):9-12.
14. MELD-Na (UNOS/OPTN). MdCalc. Accessed March 22, 2024. https://www.mdcalc.com/calc/78/meld-score-model-end-stage-liver-disease-12-older
15. Kaplan DE, Ripoll C, Thiele M, et al. AASLD practice guidance on risk stratification and management of portal hypertension and varices in cirrhosis.
Hepatology. 2023. doi:10.1097/HEP.0000000000000647
16. Ocreotide. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL. Accessed March 25, 2024. http://online.lexi.com
17. Vasopressin. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL. Accessed March 25, 2024. http://online.lexi.com
References
19. Garcia-Tsao G, Abraldes JG, Berzigotti A, et al. Portal hypertensive bleeding in cirrhosis: risk stratification, diagnosis, and management: 2016 practice
guidance by the American Association for the study of liver diseases. Hepatology. 2017;65(1):310-335. doi:10.1002/hep.28906
20. Vilstrup H, Amodio P, Bajaj J, et al. Hepatic encephalopathy in chronic liver disease: 2014 practice guideline by the American Association for the Study
of Liver Diseases and the European Association for the Study of the Liver. Hepatology. 2014;60(2):715-735. doi:10.1002/hep.27210
21. Hepatic Encephalopathy Grades/Stages. MdCalc. Accessed March 24, 2024.
https://www.mdcalc.com/calc/674/hepatic-encephalopathy-grades-stages
22. Lactulose. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL. Accessed March 24, 2024. http://online.lexi.com
23. Rifaximin. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL. Accessed March 24, 2024. http://online.lexi.com
24. Bond GR, Caravati EM, Dart RC, et al. Guidelines for the management of acetaminophen overdose. Accessed March 22, 2024.
25. Acetylcysteine. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL. Accessed March 22, 2024. http://online.lexi.com
26. Hodgman MJ, Garrard AR. A review of acetaminophen poisoning. Crit Care Clin. 2012;28(4):499-516. doi:10.1016/j.ccc.2012.07.006
27. Glal K, El-Haggar SM, Abdel-Salam SM, et al. Allopurinol prevents cirrhosis-related complications: a quadruple blind placebo-controlled trial. Am J Med.
2023;137(1):55-64. doi:10.1016/j.amjmed.2023.09.016
28. Heckroth M, Luckett RT, Moser C, et al. Nausea and vomiting in 2021: a comprehensive update. J Clin Gastroenterol. 2021;55(4):279-299.
doi:10.1097/MCG.0000000000001485
29. Gueta I, Klempfner R, Markovitgs N, et al. Clinically significant incidental QTc prolongation is subject to within-individual variability. Ann Noninvasive
Electrocardiol. 2020;25(2):e12699. doi:10.1111/anec.12699
30. Hymel N, Davies M. Evidence-based antiemetic decision tool for management of postoperative nausea and vomiting in patients at high risk of QT
prolongation and patients receiving neurotransmitter-modulating medications. AANA J. 2020;88(4):312-318.
31. Methylprednisolone. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL. Accessed March 25, 2024. http://online.lexi.com
32. Chlorpromazine. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL. Accessed March 25, 2024. http://online.lexi.com
33. Rome IV Diagnostic Criteria for Cyclic Vomiting Syndrome. MdCalc. Accessed March 25, 2024.
https://www.mdcalc.com/calc/10299/rome-iv-diagnostic-criteria-cyclic-vomiting-syndrome
34. Venkatesan T, Levinthal DJ, Tarbell SE, et al. Guidelines on management of cyclic vomiting syndrome in adults by the American Neurogastroenterology
and Motility Society and the Cyclic Vomiting Syndrome Association. Neurogastroenterol and Motil. 2019;31. doi:10.1111/nmo.13604
35. Cyclic Vomiting Syndrome. The Ohio State University Wexner Medical Center. Accessed March 26, 2024.
https://wexnermedical.osu.edu/digestive-diseases/cyclic-vomiting-syndrome
References
36. Cannabinoid Hyperemesis Syndrome Clinical Pathway. Johns Hopkins All Children’s Hospital. Accessed March 25, 2024.
https://www.hopkinsmedicine.org/-/media/files/allchildrens/clinical-pathways/chs_pathway-5_19_23.pdf
37. Sabbineni M, Scott W, Punia K, et al. Dopamine antagonists and topical capsaicin for cannabinoid hypermesis syndrome in the emergency
department: a systematic review of direct evidence. Acad Emerg Med. 2023. doi:10.1111/acem.14770
38. Ruberto AJ, Sivilotti ML, Forrester S, et al. Intravenous haloperidol versus ondansertron for cannabinoid hyperemesis syndrome (HaVOC): a randomized,
controlled trial. Ann Emerg Med. 2021;77(6):613-619. doi:10.1016/j.annemergmed.2020.08.021

Gastrointestinal Disorders Medicine Didactics Lecture

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Gastrointestinal

02 Liver Disease & Complications

03 Nausea & Vomiting

Gram-Positive Aerobic Organisms

Anaerobic Organisms (most common in infections of the small

Recurrent CDI Episodes: Same recommendation as above*✝^

Fulminant Disease: Vancomycin 500 mg PO QID x 14 days*^

*Vancomycin 125 mg PO QID x 10 days is an alternative option

Mild Disease Cure Severe Disease

Significance p = 0.006 p = 0.36 p = 0.02

*Laura Gillespie, our ID pharmacist, collected one

Zhang J, Chen L, Gomez-Simmonds A, et al.

Smith A, Baumgartner K, Bositis C. Cirrhosis: diagnosis and management. Am Fam

Biggins SW, Angeli P, Garcia-Tsao G, et al.

Encephalopathy None Grade 1 or 2 Grade 3 or 4

Bilirubin (μmol/L) < 35 35-50 > 50

Albumin (g/L) > 35 28-35 < 28

INR ≤ 1.7 1.71-2.3 > 2.3

Indicates severity of cirrhosis: Child-Pugh A: 5-6 points

MELD-Na (UNOS/OPTN). MdCalc. Accessed March 22, 2024.

Vasopressin: Directly constricts mesenteric arteries reducing

Diagnosis: Calculation of serum albumin ascites gradient ≥ 1.1

Rifaximin 550 mg PO BID or 400 mg PO TID

Vasoconstriction and renal

Non-ICU Patients: Midodrine, ocreotide (SQ or IV), and

Renal replacement therapy may be necessary

Duration: Treat for 2 weeks or until patients renal function is

Treatment: Ceftriaxone 1 g IV QD x 5-7 days

Treatment: Ceftriaxone 1 g IV QD x 5-7 days

GERD Agents: Prefer famotidine and esomeprazole (must dose

GERD Agents: Prefer famotidine and esomeprazole (must dose

Metformin: Puts patients at greater risk for lactic acidosis, avoid in

Within 4 hours of ingestion: Activated charcoal 1 g/kg x 1

N-Acetylcysteine (Acetadote ®)*

Mechanism: Thought to be related to reduction in oxidative

Heckroth M, Luckett RT, Moser C, et al. Nausea

Side Effects: Extrapyramidal symptoms, hypotension (Compazine),

Side Effects: Dry mouth, urinary

Side Effects: QTc prolongation, headache, constipation

Side Effects: Hypotension, neutropenia, fatigue

Speciﬁc dopamine antagonists are preferred based on several

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