IC5 Management of GI Flashcards
what are the emesis pathways in CINV
peripheral pathway
- chemotherapy induces enterochromaffin cells in the GI to release serotonin –> bind to 5HT3 receptors of the vagal afferent triggering ACUTE CINV
central pathway
- chemotherapy induces chemoreceptor trigger zone (CTZ) in the CNS –> substance P release –> activate NK1 receptor –> trigger DELAYED CINV.
what are the different types of CINV?
acute
delayed
breakthrough
anticipatory
refractory
describe acute CINV
onset 1-2 hours after chemotherapy
peak 5-6 hours
resolution 24hours
describe delayed CINV
onset 48-72 hours
diminish after 1-3 days.
describe anticipatory CINV
uncontrolled emesis prior to chemotherapy, associated with environmental cues eg smell of chemotherapy room
describe breakthrough CINV vs refractory CINV
breakthrough = N/V despite preventive therapy
refractory = N/V in subsequent cycles when antiemetic prophylaxis or rescue therapy has failed in previous cycles
what are the patient risk factors for CINV?
1) young age <50
2) female gender
3) hx of chemo related emesis
4) hx of motion sickness
5) hx of emesis in past pregnancy
6) anxiety
7) low prior alcohol intake <1 glass per day
(1 and 2 impt, commonly missed out)
what is the low risk antiemetic regimen
5HT3
or
DEXA
or DOPA
(no need for delayed treatment)
what is the high risk antiemetic regiment
d1 (acute) GIVEN BEFORE CHEMOTHERAPY
NK1 + 5HT3 + DEXA
+/- olanzapine
(delayed)
DEXA (d2-4)
+/- olanzapine (d2-4 if added previously)
what is the minimal risk antiemetic regimen
should not be offered routine prophylaxis
what is the moderate risk antiemetic regiment
d1 (acute)
5HT3 + DEXA
(delayed)
DEXA (d2-3)
what is the dose of nk1 antagonist
aprepitant (emend)
PO 125mg day1
80mg d2,3
what is the dose of 5HT3 antagonist
IV/PO ondansetron 8-16mg OD d1
IV/PO granisetron 1mg OD d1
what is the dexamethasone dose
IV/PO 12mg OD day 1
IV/PO 8mg OD day 2 onwards
what is the combination 5HT3 + NK1 antagonist dose?
akynzeo = netupitant 300mg + palonosetron 0.5mg
PO 1 cap OD day 1
what is the dopamine antagonist dose
metoclopramide IV/PO 10mg OD-TDS
side effects of nk1 receptors antagonist (common)
fatigue
weakness
hiccups
nausea
what is the moa of nk1 receptor antagonist
prevents substance p from binding to the receptor thus reducing vagal afferent signals to exert antiemetic effect
side effects of akynzeo
headache
constipation
mild fatigue
drug interactions of nk1 receptors antagonist
warfarin (2c9 induction)
steroids (3a4 inhibition) eg budesonide
benzodiazepines (increased BZP conc due to reduced metabolism; 3a4 inhibition) eg diazepam
some chemotherapy agents like ifosfamide (decrease ifosfamide metabolism)
due to inhibition of CYP3A4 and induction of 2C9
moa of 5ht3 receptor antagonists?
blocks 5ht3 receptors peripherally in the gi tract
and
centrally in the medulla
what are the comparisons between the diff 5ht3RA available?
ondansetron = shortest acting
granisetron = intermediate acting (expensive)
palanosetron = longest acting
SE of 5HT3 RA
headache and consitpaiton
rare: QTC prolongation
(caution in patients with underlying cardiac disease eg bradycardia, CHF, electrolyte abnormalities.
ADR of dexa
common: transient increase in glucose, insomnia (dont take late at night),
anxiety,
gastric upset (take with food)
less common: psychosis,
reactivation of ulcers
olanzapine moa
antagonist of dopamine, serotonin, histamine, cholinergic
dose of olanzapine
5 to 10mg OD
consider 2.5mg for elderly
ADR of olanzapine
fatigue,
sedation,
postural hypotension,
anticholinergic SE
indications for metoclopramide
used for acute CINV therapy in low emetic regimens
used for breakthrough CINV
moa of metoclopramide
Blockade of dopamine receptors in the chemoreceptor trigger zone;
stimulation of
cholinergic activity in the gut, increasing (forward) gut motility;
and antagonism of peripheral serotonin receptors in the intestines.
ADR of metoclopramide
mild sedation
diarrhoea
EPSE (dystonia = muscle stiffness and spasms, twitching or difficulty in speaking or swallowing; akathisia =restlessness )
counselling points with metoclopramide
avoid taking with olanzapine
increases risk of EPSE and toxicity
- tardive dyskinesia = Uncontrollable movements (such as in the face, tongue, jaw or other parts of the body)
- neuromalignant syndrome = fever, stiffness, confusion, irregular BP
IMPORTANT to separate during the first two days of their antiemetic regiment + not a big concern since PRN dosing and low dose.
counsel patient to watch for these symptoms.
indication for benzodiazepines
anticipatory CINV
moa of BZP for CINV
BIND to BZP receptors on post synaptic GABA neuron to enhance inhibitory effect of GABA
dosing for BZP for CINV
PO alprazolam 0.5-1mg
OR
PO lorazepam 0.5-2mg
on the night before chemotherapy AND 1-2h before chemo
ADR of BZP
drowsy
dizziness
hypotension
anterograde amnesia
paradoxical reactions
caution elderly = risk of falls
what are some adjunctive agents for CINV
for refractory CINV
= butyrophenones (haloperidol)
= phenothiazines (prochloperazine, promethazine, chlorpromazine)
both block dopamine receptors in CTZ
dose AND side effect of butyrophenones (haloperidol)
po / iv 0.5 mg q4-q6h
sedation, EPSE, etc
dose and side effect of phenothiazines
prochloperazine po 10mg TDS- QDS prn
adr: SEDATION, hypotension, EPSE (including dystonia, akathisia)
- same as meto
when to consider IV
IF ongoing vomiting
considerations for breakthrough CINV
fluid repletion and hydration for losses.
reassess next cycle antiemetics
cnsider use of several agents utilizing different mechanism of actions (AND diff drug class) if necessary
check for adherence
non phx strategies for CINV
1) take small, frequent meals
2) avoid greasy, spicy, very sweet/salty food OR food with strong flavours/smells
3) sip small amounts of fluid instead of full glass
4) avoid caffeinated beverages
5) avoid lying flat 2h after eating
management of multi day regimens
Give appropriate prophylactic therapy for expected
emetogenicity on each day of chemotherapy administration
* Continue delayed prophylaxis alone for 2-3 days after completion of
chemotherapy if indicated
management of anticipatory CINV
use optimal anti emetic therapy during every cycle of treatment
relaxation and systematic desensitisation
hypnosis/guided imagery
music therapy
acupuncture/acupressure
use of BZP before treatment
complications of chemotherapy induced diarrhoea
abnormal electrolytes
inappropriate fluid balance
malnutrition
renal failure
weight loss
fatigue
dehydration
risk factors for CID
> 65 yo
female
ECOG performance status ≥2
bowel inflammation/malabsorption
bowel malignancy
biliary obstruction
x6
predictive factors for CID
1st chemo
chemo duration more than 3 weeks
concomitant neutropenia
associated sx: anemia, anorexia, vomiting, mucositis
mechanism of CID
direct damage and inflammation of the intestinal mucosa resulting in imbalance between absorption and secretion.
severity grading for CID
GRADE
1) increase <4 per day above baseline
2) 4-6 + limit ADL
3) ≥7 + hospitalisation + limit self care
4) life threatening and urgent intervention needed
criteria for complicated vs uncomplicated CID?
uncomplicated
- grade 1 and 2
- no complications
complicated
- grade 3 and 4
- grade 1 and 2 with complicating sx of atleast ≥1
= cramps, grade 2 N/V
= fever, sepsis, neutropenia
= frank bleeding (eg haemorrhoids, fissures)
= dehydration
mechanism of loperamide
opioid inhibiting smooth muscle contraction in intestine to decrease motility
management of uncomplicated diarrhoea
for grade 2 = withhold chemo until sx resolve OR reduce dose
diet = oral rehydration with 8-10 glass of clear liquid
loperamide 4mg STAT then 2mg every 4h or after each episode (no max dose), continue until 12hour free of diarrhoea…
if improvement after 12-24h, continue diet modification and begin to add solid foods
if persist after 12-24h,
- loperamide 2mg q2h
- PO abx (IMPT)
- if progress to complicated = treat accordingly
- if after another 12-24 (with loperamide), stop loperamide, start octreotide or second line agent (FYI).
goals of therapy for CID
decrease mortality and morbidity
improve QOL and ADL
improve recovery of intestinal mucosa
decrease hospitalisation
management of complicated diarrhoea
withhold chemotherapy and restart with lower dose
octreotide SC 100-150mcg TDS or 25-50mcg/hr continuous IV
= increments of 50mcg after 24h
= increase to max 500mg TDS
start IV fluid hydration
start IV abx (cipro x7days)
adr of loperamide
n/v
dry mouth
dizzinss
drowsiness
rash
constipation
bloating
abdominal pain
define irinotecan ACUTE diarrhoea
EARLY ONSET
onset within 24h after admin
mean sx duration 30min
dose dependent = more sx during infusion
mainly due to acute cholinergic properties
ADR of octreotide (IMPT)
bradycardia, arrhymia
constipation, abdo pain, n/v
headache, dizziness
enlarged thyroid
octreotide moa
decrease hormone secretion =
1)increased transit time within intestines,
2) decreases secretion of fluid,
3) increased absorption of fluids and electrolytes
non phx management of CID
PROBIOTICS with lactobacillus (IMPT)
avoid alcohol, caffeine, fruit juice, lactose foods, spicy foods, high fibre foods, high fat foods, dietary supplements with high osmolarity
eat small frequent meals
BRAT diet (banana, rice, applesauce, toast)
> 3L of clear fluids containing sugar and salt
avoid lactose foods a week after CID resolution
mechanism of irinotecan diarrhoea
conversion in liver to active metabolite SN38
- enterohepatic recycling
- 100-1000x more cytotoxic in parent drug + main diarrhoea cause
causing crypt ablation, villus blunting, atrophy of epithelium of small/large intestine
risk factors for irinotecan diarrhoea
1) homozygous for UGT1A1*28 = decreased expression of UGT1A1, responsible for conversion to SN38-G (deactivation by glucoronidation)
2) bacteria in gut produce beta glucoronidase = reactive SN38-G to SN38 via deconjucation
management of irinotecan associated ACUTE diarrhoea including MOA
SC/IV atropine 0.25-1mg (max 1.2; usually sc)
MOA; inhibit acetylcholine at msucarinic receptor via competitive antagonism.
- note irinotecan is a reversible, selective acetylcholine esterase = cause cholinergic response
SE of atropine, C/I
insomnia, dizziness
tachycardia, blurred vision, dry mouth, consipation
contrdinciation in glaucoma
define irinotecan DELAYED diarrhoea
LATE ONSET
after 24h from admin
not dose or frequency dependent
- median 6 days with q3week dosing
- median 11 days with weekly dosing
management of irinotecan DELAYED diarrhoea
loperamide 4mg with first loose stop
then 2mg q2h (4mg q4h (night))
until 12h of no bowel movement
factors increasing risk of chemo induced constipation
1) lower fluid intake / dehydration
2) loss of appetite / anorexia
3) lack of fibre/bulk forming foods
4) vitamin or mineral supplements eg iron or calcium pills
5) overuse of laxatives
6) low lv of phy activity / alot of bed rest
7) thyroid problems
8) depression
9) high serum calcium/potassium
10) cancer growing into large intestine/pressing into spinal cord
sx of chemo induced constiaption
- Bloating or feeling of fullness
- Cramping or pain
- Gas, or flatulence
- Belching
- Loss of appetite
- No regular bowel movement for 2 or more days
- Straining to have a bowel movement
- Small hard stools that are difficult to pass
- Rectal pressure
- Leakage of small amounts of stool resembling diarrhea
- Swollen, or distended, abdomen
- Nausea or vomitng
drugs that increase consitpaiton risk
opioids
chemo drugs (vinca alkaloids: vincristine, vinblastine, vinorelbine)
antinausea (5ht3 receptors antagonists)
anticonvulsants
non phx prevention of consitpaiton
eat more fibre
eat natural laxatives
increase phy activity
phx management of constipation
stimulant laxatives
- Senna 15mg ON
bulk forming laxatives
- fibrogel 1 sachet BD (isphagula husk)
osmotic laxatives /stool softener
- lactulose 10-15ml TDS
- macrogol (forlax 1 sachet BD)
enemas and suppositories
- enemas clean out bowel or deliver laxatives eg fleet phosphate enema
when should suppositories and enemas be avoided
low WBC or platelet count due to infection risk OR bleeding.
grading for mucositis induced by chemo
WHO:
0) NO EVIDEENCE
1) erythema and soreness
2) ulcers, can eat solids
3) ulcers, liquid diet
4) ulcers, cannot PO
5) n/a
CCTAE
0) NA
1) Asymptomatic or mild, no intervention
2) moderate pain, modified diet
3) severe pain, interfere with PO
4) life threatening
5) death
risk factors for chemo induced mucositis
PATIENT RELATED
- autoimmune disorder
- diabetes
- female
- folic acid or vit b12 deficiency
CHEMOTHERAPY (risk increases with any other factors that increase dose and frequency)
RADIOTHERAPY (furhter increased with smoking, alcohol, or presence of xerostomia/infection)
goals of therapy for chemo induced mucositis
prevent and decrease severity
manage pain and associated sx
prevent chemo delays or dosage reductions
recommend measures to prevent mucositis
1) paliferm after high dose chemo and TBI for autologous HSCT
2) benzydramine hcl mouthwash after radiation
3) oral cryotherapy
palifermin dosing
keratinocyte growth factor
- reduce duration and severity
- iv 60mcg/kg/day for three consecutive days before and after myelotoxic therapy (total 6)
= third dose 24-48h prior
= forth dose on same day as HSCT and within 4 days of third dose
how does oral cryotherapy help
reduces mucositis by causing vasoconstriction and decreasing blood flow to the GI mucosal
recommended treatment strategies for mucositis
Oracare Suspension (Nystatin
125,000U, Tetracycline 62.5mg,
hydrocortisone 5mg,
diphenhydramine
11.5mg/10mL)
Mylocaine suspension
(diphenhydramine 11.5mg,
lignocaine 16.7mg/10mL)
Morphine sulfate solution
1mg/mL
counselling for treatment strateiges for mucositis
mylocaine and morphine
meant to stop pain before meals.
take 15min - 1h before
then
oracare after food to remove bacteria
SAFE TO SWLLOW
AVOID ALCOHOL BASED
other formulations for mucositis treatment
oracort (lidocaine + triamcinolone)
soragel (choline salicylate)
difflam spray (benzydamine)
difflam gargle
non phx tx of mucostitis
oral 7 mouthwash
bioxtra mouthwash
AVOID ALCOHOL BASED like listerine = drying effect may cause xerostomia (mouth dryness)
