Diarrhea

WHO Definition:

The passage of more than 3 unformed stools in 24 hours .

OrFrequent passage of loose stools with urgency.

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

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 Flu2. Capecitabine3. Irinotecan4. Taxanes5. 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

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

5 -Fluorouracil

Risk factors 1. Older age2. Coadministration with Leucovorin 3. Bolus rather than infusion4. Associated bowel disease5. Female gender

DPD deficiency

DPD deficiency

Life-threatening complication including:

1. Sever diarrhea2. Sever mucositis3. 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 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

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

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

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)

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 motilityDose:

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)

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

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