Nausea & Vomiting - PowerPoint Presentation

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Nausea & Vomiting

Dr. Lucy Harris

SpR

Palliative Medicine

September 2014Slide3

A 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 glottisSlide4

It’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.Slide5

Why 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.

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Pathophysiology

Emetic process not fully understood

Awareness of physiology of vomiting and main neurotransmitters involved can help in assessment and choice of appropriate anti-emeticSlide7

Cortex

CTZ

Vestibular

GI

VOMITING

CENTRE

(Medulla)

VOMITING REFLEXSlide8

Receptor

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)Slide9

The

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 musclesSlide10

Consideration 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.Slide11
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Management 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, DrugsSlide13

Principles 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 & vomitingSlide14

Non-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 / AcupunctureDistractionSlide15

Approach to Anti-emetics:

Anticipate

Regular

doses and

consider most appropriate route of delivery

Target the relevant receptors according to cause

Consider

Combination Slide16

Antiemetic

Choice – Think receptors!Slide17

Stimulus

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 PathwaysSlide18

Mike 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

ProchlorperazineLevomepromazineSlide19

Management

PharmacologicalSlide20

Other 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 effectSlide21

Antiemetic Ladder

STEP 2

2nd line narrow spectrum

eg

ondansetron

OR combination

eg

cyclizine+haloperidol

OR broad spectrum

eg

levomepromazine STEP 1Narrow spectrumMetoclopramideCyclizineHaloperidolSlide22

Route 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)Slide23

Additional 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!Slide24

Summary

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. Slide25

Cause 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 / 24hrsSlide26

Pharmacokinetics 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-pyramidalSlide27

Questions?