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Diarrhea
WHO Definition:
The passage of more than 3 unformed stools in 24 hours .
OrFrequent passage of loose stools with urgency.
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NCI Grading of DiarrheaGrade 0None
Grade 1 <4 stools / day
Grade 24-6 stools / dayModerate crampingNot interfering with normal activity
Grade 37 -9 stools / daySever cramping and incontinence
Interfering with normal activity
Grade 4 >10 stools / dayGrossly bloody diarrheaNeed hospital admission
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Causes of diarrhea in cancer paients
Chemotherapy induced diarrhea Infectious diarrhea Entral feeding Celiac plexus block Radiotherapy induced diarrhea Paraneoplastic syndrome
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Chemotherapy induced diarrhea
The most common CTh agents causing diarrhea are:
1. 5 Flu2. Capecitabine3. Irinotecan4. Taxanes5. Target agents “ Sunitinib, Sorafanib,
Erlotinib, Gefitinib ….”
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5 -Fluorouracil
Mechanism of action: 5- FLUOROURACIL decrease the biosynthesis of
pyrimidine nucleotides by inhibiting thymidylate synthase, the enzyme that catalyzes the rate limiting step in DNA synthesis.
Leucovorin increases binding of 5-FU to thymidylate synthase thereby increasing 5-FU t1/2
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Mechanism of Diarrhea with 5 Flu:
5 -Fluorouracil
5-Flu causes mitotic arrest of intestinal crypts cells
Abnormal secretion of electrolytes and fluids
Increase in the ratio of immature secretory crypt cells to mature villous enterocytes
Diarrhea
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5 -Fluorouracil
Risk factors 1. Older age2. Coadministration with Leucovorin 3. Bolus rather than infusion4. Associated bowel disease5. Female gender
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DPD deficiency
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DPD deficiency
Life-threatening complication including:
1. Sever diarrhea2. Sever mucositis3. Pancytopenia
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Capecitabine “Xeloda”
Capecitabine, a precursor of 5-FU, is an oral fluoropyrimidine cytotoxic agent developed with the aim of providing a more effective , less toxic and oral drug.
It is converted in vivo to 5-FU The prevelance of diarrhea is 30% -
40%.
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Irinotecan “Campto”
Topoisomerase I inhipitor(Topoisomerase I relaxes the supercoiled DNA for variety of cellular processes)
2 Types of diarrhea may occur:1. Acute diarrhea (immediately after drug administration
and usually respond to atropine)
2. Delayed diarrhea (24 hrs after drug administration)
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Irinotecan “Campto” cont.
Mechanism of diarrhea:
Destructive effect of active agent on the intestinal colonic Epithelium
+Production of pro-inflammatory cytokines
Disturbance in absorptive and secretory functions of mucosa
Diarrhea
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Assessment History and physical examination:
( Don’t forget Vital signs and signs of dehydration)
Dietary history and medical history Grading of diarrhea
Grade 0None
Grade 1 <4 stools / day
Grade 24-6 stools / dayModerate crampingNot interfering with normal activity
Grade 37 -9 stools / daySever cramping and incontinence
Interfering with normal activity
Grade 4 >10 stools / dayGrossly bloody diarrheaNeed hospital admission
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Assessment cont.
Complete lab.1. CBC2. RFT3. LFT4. Bl. Sugar
( Don’t forget Electrolytes) Stool analysis Blood culture if patient feverish
Imaging according to patient complaint
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General principles in the management of CTH induced diarrhea
1. Rule out other causes of diarrhea2. Diet Modification: e.g.
* Increase Fluid intake* Fresh diet
3. Anti-diarrheal medications
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Anti-diarrheal medications
A. LoperamideMech: Reduces stool frequency Decrease bowel movementDose:4 mg followed by 2mg every 2-4 hrs or
after every unformed stool (up to 16 mg /day)
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Anti-diarrheal medications cont.
B. Atropine – diphenoxylate“Lomotile”
Dose:1-2 tablets every 4-6 hours
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Anti-diarrheal medications cont.
C. Octreotide“Sandostatine”
Mech: Somatostatine analogue Suppression insulin, glucagone, VAIP and
pancreatic exocrine function Suppress intestinal motilityDose:
100 – 150 mcg SC/IV 3 times /day “up to 500 mcg /day” according to response
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How to manage?
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Grade 1-2 Diarrhea
Dietary management Loperamide
4mg then 2mg after loose stool( max 16 mg /day)
Not resolvedHigh dose loperamide
4mg then 2mg/2hrs
Diarrhea resolvedAdjust diet and Stop loperamide after
12 hrs without diarrhea
Not resolved after 24 hrsOcteroides 100 – 150 mcg
+Fulid and elect. reeplacement
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Grade 3-4 Diarrhea
Hospital admitionAnd
Loperamide 4mg then 2mg after loose stool (max 16 mg /day)Octeroide 100 – 150 mcg
Fluid and elect. Replacement + Consider antibiotic+
Not resolved after 24 hrsIncrease Octeroide up to 500 mcg / day
or 25-50 mcg/hr continuous infusion
+High dose loperamide