Oncology – Symptomatic Diarrhea Management
Drug causing s+sx:
Symptoms & Signs:
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Abundant diarrhea
o Defined as >= 1 of:
o increased freq of BM (>=3/24hrs)
o decreased stool consistency
o increased stool weight (>200g/24hrs)
Diarrhea can lead to Sx:
o Fluid loss / Weight loss
o Fatigue
o Electrolyte imbalances
o Fatigue / weakness
o malnutrition
Diarrhea can include blood but is rare
Acute vs Chronic Diarrhea from Chemotherapeutic Agents:
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1st
Acute: usually within
few days of Tx and subsides
within 72 hours of O/S
Chronic: usually delayed O/S and freq attacks over
extended time period (note: Therapeutic Choices
defines chronic diarrhea as that which persists > 14d)
Risk Factors:
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See disease and drug causes
Female sex
increased age
Pts with cancer + IBD
Urgency / Tx Necessary?
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Can lead to malnutrition, fluid loss, electrolyte
changes
This may delay further chemotherapy treatment until
patient is recovered
Compliance may become an issue if chemo diarrhea
becomes unbearable
Pathophysiology:
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Chemo agents can cause diarrhea mainly via 2
mechanisms:
1) Secretory – a change in active ion transport
(increased Cl secretion / decreased Na or
decreased water absorption)
o This will not be affected by fasting
2) Exudative - increased in tissue hydrostatic
pressure due to disruption of intestinal mucosa
through inflammatory and ulcerated lesions
o
o
o
o
o
o
o
o
o
o
Antibiotics (Clinda, MTZ, PCN, Erythro)
Laxatives
Antacids (Mg-containing)
Colchicines
Methyldopa
Pro-kinetic agents (e.g.metoclopramide)
Bile-acid resins (e.g.cholestyramine)
NSAIDs
Osalazine
Chemotherapeutic Agents (idarubicin, epirubicin,
pentostatin, mitoguazone, mitoxantrone,
docetaxil, teniposide, flucytosine, 5-FU,
irinotecan)
Mechanisms of diarrhea induced by antineoplastics:
o 5-FU inhibits mitotic activity of crypt cells, causing
relative increase in immature crypt cells (secrete fluid
into lumen); also causes damage to villi cells
(secretory diarrhea)
o Irinotecan
1)acutely (<24h) causes a cholinergic effect (abd cramps,
diaphoresis, lacrimation, etc.)
Tx: ATROPINE dosage 0.25-1mg IV (IM possible)
SE: anticholinergic (dry mouth, constipation, hypotension,
tachycardia, may get heart block)
2)chronically causes a delayed (1d-2w post admin),
caused by SN38, a metabolite of irinotecan which is
cycled through enterohepatic circulation
Peak effect is at 11 days. Acts to increase secretion
Goal of therapy:
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Minimize side effects of chemo
Prevent complications (lytes, hydration, nutrition)
Non-Pharm Options:
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Drink 8-12 (250mL) glasses of H20/d or,
Pedialyte/Gastrolyte/Gatorade diluted 50:50 with H20
Can increase K with the BRAT diet
Avoid coffee, alcohol, fried foods, dairy until diarrhea
subsides
Pharmacological Options
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See chart below
Conditions causing s+sx (Differential Dx):
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Gastrointestinal cancer (bowel, pancreas…)
IBD
Infections
Infection (C. diff. Infxns marked by blood, fever)
Graft-versus-host Dx (GVHD)
Surgery
Thyroid/Endocrine Dx
Food poisoning
Malabsorptive Dx
Radiation Tx
Bowel resection
1
Drug – MOA
Place in Tx/ Efficacy
SEs
CI/DI
Dosage
Cost
Intestinal Transit
Inhibitors (opioids and
opioid derivatives)
–chronic chemo induced diarrhea
1) Loperamide – best efficacy
in class
2) Diphenoxylate+atropine
(Lomotil) – less effective
than Loperamide
3) Codeine – less effective and
causes sedation
Note acute diarrhea usually Tx in
Hosp with IV/SC atropine
O/S 40-60 min
DUR 3-4 hrs
– sedation (codeine)
- Nausea
- abdom cramps
- constipation
-dry skin and mucous membrane from
atropine in lomotil (to discourage drug
abuse)
- Toxic Megacolon (esp. codeine)
can stop peristalsis and cause pooling
of stool -> dilatation and perforation
-CNS depressants
(eg EtOH,
barbiturates,
tranquilizers)
-CI if fever and
bloody diarrhea
(increased risk of
bacterial invasion)
- CI if severe
inflammatory bowel
dx (increased TM
risk)
Loperamide – 2 caps
stat, then 1 every 2
hours (or 4mg q4h)
until BM cease for 12
hrs
$
Use for refractory to opioid pts
(due to side effects)
-Hypotension
-dizziness
-sedation
-dry mouth
-constipation
(anti cholinergic SEs)
-antihypertensives
-TCA
-CNS depressants
0.1-0.6mg bid (start
at 0.1 and titrate up
to 0.6)
-stop upward titration
if diarrhea stops of
hypotension occurs
$
-pain at injection site
-n/v
-hypothyroidism
-blood sugar changes -> monitor if
DM patient
-tachycardia
-edema
-cholelithiasis (long term at hi dose)
-antihypertensives
(caution -> mon
BP)
-caution insulin and
OHA (mon BG)
100-600mcg SC/IV
bid-qid)
-depo IM formulation
for chronic diarrhea
(eg caused by
endocrine problems)
$$$$
-nausea
-constipation
-fat soluble vitamin (ADEK) deficiency
chronically
Interfered
absorption of many
drugs (spread out
admin 2-3 hours)
Cholestyramine: 4g
q6h w/ lots of fluid
$-$$
- bind to opioid R in
intestinal wall efferent
nerve endings ->
decrease Ach release
(slows motility)
decrease intestinal
secretion
increase absorption
increase anal sphincter
tone
Proabsorptive Agents
(clonidine)
-binds to alpha 2 receptors
->
decreased intestinal
secretion
increased absorption
decreased motility
Antisecretory
sandostatin (Octreotide),
Somatostatin
-bind to somatostain R (Gprotein linked, decreased
cAMP)
-decreased motility
-decreased gastric and
pancreatic secretion
-increased absorption
(lytes and H20)
Intraluminal Agents (e.g
clays, cholestyramine)
(NB bismuth subsalycilate can be
used but no evidence for this
purpose, psylium ineffective for
chronic opioid use)
-bind intestinal contents
-increase stool consistency
Monitoring
Oncology - Diarrhea
O/S 60 min
DUR 6-10 hrs
-For neuroendocrine tumour induced
diarrhea (VIPoma, carcinoid)
-for 5-FU and cisplatin diarrhea
O/S sandostatin more rapid than
somatostatin
DUR – sando 6-12 hrs, somato
shorter
-radiation induced colitis (Cholesty)
-use limited due to interference of
drug absorption
Lomotil (2.5mg) –
max 15-20mg/day
divided t-qid
Codeine – 30-60mg
q4h prn
O/S 30-60 min
DUR 6-10h?
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Diarrhea (freq, amt, consistency)
Complications (dehydration -> confusion, dizziness cramps), nutrition
(weight)
2
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Signs of infxn (blood, mucus, fever >= 38C) -> go to ER
Oncology - Diarrhea
3