Download Diarrhea

Diarrhea
WHO Definition:
The passage of more than 3 unformed
stools in 24 hours.
Or
Frequent passage of loose stools with
urgency.
NCI Grading of Diarrhea
Grade 0
None
Grade 1
< 4 stools / day
Grade 2
4-6 stools / day
Moderate cramping
Not interfering with normal activity
Grade 3
7- 9 stools / day
Sever cramping and incontinence
Interfering with normal activity
Grade 4
> 10 stools / day
Grossly bloody diarrhea
Need hospital admission
Causes of diarrhea in cancer paients






Chemotherapy induced diarrhea
Infectious diarrhea
Entral feeding
Celiac plexus block
Radiotherapy induced diarrhea
Paraneoplastic syndrome
Chemotherapy induced diarrhea
 The most common CTh agents
causing diarrhea are:
1. 5 Flu
2. Capecitabine
3. Irinotecan
4. Taxanes
5. Target agents “ Sunitinib, Sorafanib,
Erlotinib, Gefitinib ….”
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
5- Fluorouracil
 Mechanism of Diarrhea with 5 Flu:
5-Flu causes mitotic arrest of intestinal crypts cells
Increase in the ratio of immature secretory crypt cells to
mature villous enterocytes
Abnormal secretion of electrolytes and fluids
Diarrhea
5- Fluorouracil
 Risk factors
1.
2.
3.
4.
5.
Older age
Coadministration with Leucovorin
Bolus rather than infusion
Associated bowel disease
Female gender
DPD deficiency
DPD deficiency
 Life-threatening complication
including:
1. Sever diarrhea
2. Sever mucositis
3. Pancytopenia
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%.
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)
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
Assessment
 History and physical examination:
( Don’t forget Vital signs and signs of dehydration)
 Dietary history and medical history
 Grading of diarrhea
Grade 0
None
Grade 1
< 4 stools / day
Grade 2
4-6 stools / day
Moderate cramping
Not interfering with normal activity
Grade 3
7- 9 stools / day
Sever cramping and incontinence
Interfering with normal activity
Grade 4
> 10 stools / day
Grossly bloody diarrhea
Need hospital admission
Assessment
cont.
 Complete lab.
1.
2.
3.
4.
CBC
RFT
LFT
Bl. Sugar
( Don’t forget Electrolytes)
 Stool analysis
 Blood culture if patient feverish
 Imaging according to patient complaint
General principles in the management of
CTH induced diarrhea
1. Rule out other causes of diarrhea
2. Diet Modification:
e.g.
* Increase Fluid intake
* Fresh diet
3. Anti-diarrheal medications
Anti-diarrheal medications
A. Loperamide
Mech:
 Reduces stool frequency
 Decrease bowel movement
Dose:
4 mg followed by 2mg every 2-4 hrs or
after every unformed stool (up to 16
mg /day)
Anti-diarrheal medications
cont.
B. Atropine – diphenoxylate
“Lomotile”
Dose:
1-2 tablets every 4-6 hours
Anti-diarrheal medications
cont.
C. Octreotide
“Sandostatine”
Mech:
 Somatostatine analogue
 Suppression insulin, glucagone, VAIP and
pancreatic exocrine function
 Suppress intestinal motility
Dose:
100 – 150 mcg SC/IV 3 times /day “up to
500 mcg /day” according to response
How to manage ?
Grade 1-2 Diarrhea
Dietary management
Loperamide
4mg then 2mg after loose stool
(max 16 mg /day)
Diarrhea resolved
Adjust diet and Stop loperamide after
12 hrs without diarrhea
Not resolved
High dose loperamide
4mg then 2mg/2hrs
Not resolved after 24 hrs
Octeroides 100 – 150 mcg
+
Fulid and elect. reeplacement
Grade 3-4 Diarrhea
Hospital admition
And
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 hrs
Increase Octeroide up to 500 mcg / day
or
25-50 mcg/hr continuous infusion
+
High dose loperamide