SpR Palliative Medicine September 2014 A Starting Point Definitions Nausea An unpleasant sensation of the need to vomit often accompanied by autonomic symptoms sweating salivation tachycardia ID: 914530
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Slide1
Slide2Nausea & Vomiting
Dr. Lucy Harris
SpR
Palliative Medicine
September 2014
Slide3A Starting
Point - Definitions
Nausea:
An unpleasant sensation of the need to vomit, often accompanied by autonomic symptoms – sweating, salivation, tachycardia.
Vomiting:
Forceful expulsion of gastric contents through the
mouth, caused by forceful and sustained contraction of the abdominal muscles and diaphragm.
Anticipatory vomiting:
Vomiting in the absence, but caused by
anticipation,
of the stimulus e.g. chemotherapy
Retching:
Rhythmic, laboured, spasmodic
movements of the diaphragm and abdominal muscles against a closed glottis
Slide4It’s all in the history….
Regurgitation
– The movement of contents of the stomach into the oesophagus and / or from the oesophagus into the mouth.
Rumination
– The controlled, voluntary regurgitation of undigested food from the stomach into the mouth (food often then swallowed again). Often associated with psychiatric disorders
Oesophageal secretions
- Frothy, stringy white or colourless secretions, associated with oesophageal cancer. May respond to steroids.
Slide5Why Is It Important?
About 60 % of patients with advanced cancer will experience nausea and / or vomiting at some point
Prevalence of about 40% in the last six weeks of life
More common in: Stomach / Breast Cancers
Women
Patients
under 65
Least common in: Lung Cancer
Arch Intern Med.
1986;146(10):2021-2023.
Pathophysiology
Emetic process not fully understood
Awareness of physiology of vomiting and main neurotransmitters involved can help in assessment and choice of appropriate anti-emetic
Slide7Cortex
CTZ
Vestibular
GI
VOMITING
CENTRE
(Medulla)
VOMITING REFLEX
Slide8Receptor
Sites
Cortical Structures
(
eg
. anxiety, sights, smells, raised ICP):
GABA
Vomiting Centre:
Muscarinic
(Ach)
Histamine (H1) Serotonin (5HT2)Chemoreceptor Trigger Zone: Serotonin (5HT3
) Dopamine (D2)Vestibular Apparatus: Muscarinic (Ach)
Histamine (H1)Gut Mucosa: Dopamine (D2)
Serotonin (5HT3) Serotonin (5HT4)
Slide9The
Vomiting Reflex
Involves multiple structures - the pharynx, larynx, upper GI tract, the muscles of the thorax, abdomen and diaphragm and the respiratory and
salivatory
centres.
It causes ;
1
) Nausea, with autonomic symptoms
2
) Gastric stasis
/
atony
(relaxation of smooth muscle wall of stomach)3) Retching with closure of vocal cords 4) Elevation of palate (to close nasopharynx)5) Reverse peristalsis6) Contraction of the abdominal wall and chest muscles
Slide10Consideration of Causes in the Palliative Setting
Case Example 1:
75 man,
CA
lung with
bone
metastases
lower back. Started regular
oromorph
for back pain
Complaining predominantly of nausea
.
Case Example 2:
60 women, CA breast with liver, bone and brain metastases. On morphine for several weeks. Not constipated. Complaining of N&V. Vomiting does not relieve nausea.
Slide11Slide12Management Approach….
ESTABLISH THE CAUSE
Urine Dip, U&Es,
Calcium, Relevant Drug Levels,
?AXR, Brain imaging
Hydration, Temperature, Mouth, Abdomen,
Rectum, Fundi, Neurology
Onset, Timing,
N vs V, Triggers, Associated factors, Content of Vomitus, Drugs
Slide13Principles of Treatment
1: Treat the cause
2: Non-pharmacological approaches
3: Anti-emetics
The
most common mistakes in treating nausea & vomiting are:
not considering reversible factors
using
oral
route for anti-emetics in established nausea & vomiting
Slide14Non-Pharmacological
Approaches
Control Malodour (
eg
:
fungating
tumours)
Consider environment - away
from sight and smell of food
. Ask others to take on role of food preparation
Meal Size - Small
snacks
regularlyComplementary
Therapy eg: acupressure bands / AcupunctureDistraction
Slide15Approach to Anti-emetics:
Anticipate
Regular
doses and
consider most appropriate route of delivery
Target the relevant receptors according to cause
Consider
Combination
Slide16Antiemetic
Choice – Think receptors!
Slide17Stimulus
Area
Receptors
Drugs,
Metabolic
Chemoreceptor trigger zone
D2
5HT3
Motion,
Position
Vestibular
Muscarinic (Ach)
Histamine
Visceral
Organs
D2
5HT3
? Non-specific
CNS
Cannabinoid
↑
ICP
Cerebral cortex
Histamine
Mike Harlos, Manitoba
Receptors in Vomiting Pathways
Slide18Mike Harlos, Manitoba
Antiemetics
– site
of action
CTZ
Haloperidol
Metoclopramide
Domperidone
Levomepromazine
Ondansetron
Granisetron
GI
Metoclopramide
Domperidone
OndansetronGranisetron
VOMITING
CENTRE
Vestibular
Hyoscine
hydrobromide
CyclizineProchlorperazine
LevomepromazineHyoscine hydrobromideCyclizine
ProchlorperazineLevomepromazine
Slide19Management
Pharmacological
Slide20Other drugs used to manage nausea and vomiting
Dexamethasone
Decreases permeability at CTZ, inhibits central PG synth
Ranitidine
Decreases volume of gastric secretions
Octreotide
Decreases GI
secretions (useful for large volume vomits in
malignant bowel obstruction)
PPI
Decreases acidity
Antifungals
Treat oropharyngeal candida
BenzodiazepinesFor anxiety, ??GABA effect
Slide21Antiemetic Ladder
STEP 2
2nd line narrow spectrum
eg
ondansetron
OR combination
eg
cyclizine+haloperidol
OR broad spectrum
eg
levomepromazine STEP 1Narrow spectrumMetoclopramideCyclizineHaloperidol
Slide22Route is important
Essential to consider antiemetic route if
already
vomiting
/ absorption concerns
Transdermal
:
Scopaderm
TTS releases 0.5m hyoscine
hydrobromide
/ 72 hrs
Buccal: Buccastem (Prochlorperazine tab absorbed from buccal mucosa) 3mg/12hrs Rectal: Prochlorperazine (25mg tds) Domperidone
(30-60mg qds)S/C: Cyclizine (100-150mg/24hrs) – does not combine well in csci Haloperidol (2.5-10mg/24hrs)
Levomepromazine (6.25-100mg/24hrs) (2:1 conversion for po : sc) Metoclopramide (30-120mg/24hrs)
Octreotide (100-1200mcg/24hrs)
Slide23Additional Hints
If using more than one anti-emetic,
use those that
act on different receptors
30
% pts require 2
anti-emetics
If previously on regular
antiemetics
add
to
these to a syringe driver if started for other reasonsAvoid
dopamine antagonists (esp; metoclopramide, haloperidol) in PD Reassess regularly!
Slide24Summary
N+V are common in end-stage disease, and significantly affect QOL.
Determining and reversing cause(s)
if
possible is paramount, often multi-factorial
Usually
easily treated, many anti-emetics – choice depends on cause
.
Use regular
antiemetics
, by appropriate
route, with PRN provision
Oral medication rarely works if established vomiting or severe nausea.
Slide25Cause of Vomiting
1
st
Line Antiemetic
Dose
2
nd
Line Antiemetic
Dose
Drugs / Toxins
Haloperidol
1.5-3mg nocte/bd
Levomepromazine
6.25 -25mg / 24 hrs
Radiotherapy
Ondansetron
8mg stat, then bd for 5/7
Haloperidol
1.5-3mg nocte/bd
Chemotherapy
Ondansetron
Dexamethasone
8mg stat, then bd for 5/7
4-8mg od
Metoclopramide
20mg tds/qds
Metabolic (eg.↑Ca/Uraemia)
Haloperidol
1.5mg nocte/bd
Levomepromazine
Cyclizine
6.25-25mg / 24 hrs
50mg tds
Raised ICP
Cyclizine +
Dexamethasone
50mg tds
8-16mg / 24hrs
Levomepromazine +
Dexamethasone
6.25-25mg / 24hrs
8-16mg / 24hrs
Bowel Obstruction
(with colic)
Cyclizine +/-
Buscopan +/-
Octreotide +/-
Dexamethasone
150mg / 24hrs
40-100mg /24hrs s/c
300-1000mcg/24hrs s/c
8-16mg / 24hrs
Haloperidol
Levomepromazine
+/- Buscopan / Octreotide / Dexamethasone
1.5-3mg od/bd
6.25-25mg / 24hrs
Delayed Gastric Emptying
Metoclopramide
10-20mg tds/qds
Domperidone
10-20mg qds
Gastric Irritation
PPI for gastritis
Stop irritants- NSAIDs
Cyclizine
50mg tds
Ondansetron
Metoclopramide
Levomepromazine
8mg
bd
10-20mg
tds
/
qds
6.25-25mg / 24hrs
Slide26Pharmacokinetics Of
Antiemetics
Drug
Onset of action
Duration of Action
Half-life
Mechanism Of Action
Place Of Action
Side Effects
Metoclopramide
10-15 mins
1-2 hrs
2.5-5 hrs
Prokinetic
(D2 antagonist, 5HT4 agonist, 5HT3 antagonist)
Intestinal
CTZ
Extrapyramidal
Colic (in intestinal obstruction)
Domperidone
30 mins
8-16 hrs
14 hrs
Prokinetic
(D2 antagonist)
Intestinal
Colic (in intestinal obstruction)
Cyclizine
<2 hrs
4-6 hrs
5 hrs
Anti-histamine (H1 receptor)
Anticholinergic
(ACh receptor)
Vomiting Centre
Dry Mouth
Drowsiness
Ondansetron
<30 mins PO
< 5 mins IV
12 hrs
3 hrs
5HT3 antagonist
CTZ
Constipation
Headache
Levomepromazine
1-4 hrs PO
30-90 mins SC
12-24 hrs
13-30 hrs
Broad Spectrum
(ACh, H1, 5HTs, D2 receptors)
Vomiting Centre
CTZ
Sedative
Antimuscarinic
Anxiolytic
Buscopan
1-2 hrs PO
3-5 mins SC
15 mins a/spasmotic
1-9 hrs a/secretory
5-6 hrs
Anticholinergic (ACh receptor)
Vomiting Centre
Dry Mouth
Drowsiness
Confusion
Haloperidol
10-15 mins s/c
>1hr PO
Up to 24hrs
13-35 hrs
Neuroleptic (D2 antagonist)
CTZ
Sedation
Extra-pyramidal
Slide27Questions?