8.2 (10.2) Palliation of nausea and vomiting

Question 1

What are the 3 phases of emesis

Answer 1

Prodrome, retching, vomiting

Question 2

What acts as a centre for integration of diverse stimuli (aka vomiting centre) and where is it located?

Answer 2

Nucleus Tractus Solitarius (NTS) located in dorsal medulla of the brainstem

Question 3

List 4 main afferent sources for the vomiting centre/NTS in the human brain and the NTs associated with them

Answer 3

*cerebral cortex and higher brainstem - GABA, 5HT2

*CTZ (can only initiate vomiting via the VC) - 5HT3, D, NK

*vestibular system - H1, M

*GI tract, viscera, heart and thorax (via vagus nerve) - 5HT3

Question 4

List 3 main effector pathways from NTS

Answer 4

Cerebral cortex -> nausea
Endocrine (hypothalamus, pituitary gland) -> decrease appetite
Autonomic motor nuclei -> stomach -> vomiting

Fig. 8.2.1

Question 5

List the major NTs that act on the CTZ

Answer 5

dopamine
serotonin 5HT3
neurokinin

Question 6

List the major NTs that DIRECTLY act on the VC (NTS)

Answer 6

histamine
acetylcholine
serotonin (5HT3 and 5HT2)
Neurokinin 1

(No dopamine)

Question 7

What are 2 dominant sites of NK 1 receptors responsible for emesis?

Answer 7

CTZ and NTS (both located in the medulla oblangata of brainstem)

Question 8

What are the two approaches to the selection of an antiemetic for a patient with nausea? What is generally preferred and why?

Answer 8

Two strategies have been proposed for the management of NV:
1) Etiologic based approach
2) Empirical approach.

The Etiology approach (Table 8.2.1) - recommended as more rapid relief of nausea
- involves identifying the most likely cause of the nausea, the pathways and receptors involved
- Drugs known to inhibit those particular receptors are then chosen

Question 9

You are seeing a patient in consultation for nausea. You decide to take a mechanistic approach to the selection of an antiemetic. What six steps will you take in managing the patient’s nausea?

Answer 9

1. Identify the likely cause(s) of nausea and/or vomiting
2. Identify the pathway by which each cause triggers the vomiting reflex.
3. Identify the neurotransmitter receptor involved in the identified pathway.
4. Choose the most potent antagonist (i.e. anti-emetic) to the receptor identified
5. Choose a route of administration that ensures that the drug reaches its site of action (usually not PO)
6. Titrate the dose carefully, review the patient frequently.
7. Give the antiemetic regularly.
8. If symptoms persist, review the likely cause(s): additional treatment may be required for an overlooked cause, or alternative treatment may be suggested by a different cause becoming apparent.
9. If combining antiemetics, potential drug interactions need to be considered

Question 10

List three classes of dopamine antagonists and give an example of each. Which is the most potent receptor blocker in the CTZ?

Answer 10

phenothiazines - prochlorperazine, methrotrimeprazine (note - broad spectrum)

butyrophenones - haloperidol - most potent receptor blocker or CTZ

benzamides - metoclopramide, domperidone

Question 11

What are three side effects of low potency phenothiazines and which receptors are responsible for these side effects?

Answer 11

anti-dopamine - EPS

alpha 1 adrenergic receptor - hypotension, sedation

anti-histamine - dry mouth, sedation

anti muscarinic toxicities - mad as a hatter, hot as hell, red as a beat, dry as a bone, and blind as a bat.

Question 12

List four examples of extrapyramidal symptoms that may occur from the use of dopamine antagonists

Answer 12

akathisia
acute dystonia
pseudoparkinsonism
tardive dyskinesia

Question 13

What are three predominant indications for the use of 5HT3 receptor antagonists in the management of NV

Answer 13

chemotherapy induced NV
radiotherapy NV
post operative NV

Question 14

List four common side effects of 5HT3 antagonists

Answer 14

Headache
dizziness
constipation
QTc prolongation

FS:
- GASH (uptodate) - GI, anxiety, sedation/dizzy, headache
- QTC

Question 15

For what causes of nausea would you use the following drugs?
- corticosteroids
- cannabinoids
- benzo
- octreotide
- mirtazapine
- NK1 receptor antagonist

Answer 15

• corticosteroids - intracranial tumors, bowel obstruction
• cannabinoids - Chemo-Induced N/V (CINV)
• benzo - anticipatory nausea, CINV
• octreotide - malignant bowel obstruction
• mirtazapine - nausea associated with cancer (has 5HT3 activity)
• NK1 receptor antagonist - CINV

Question 16

List 4 non pharm (alternative) techniques for NV

Answer 16

Dietary modification
- small portion, attractive presentation, cold food
- protein rich food for gastric tachyarrhythmia, nausea from chemo or motion sickness
- low fat, low fiber
- ginger (mixed results for effectiveness)

acupuncture/acupressure/TENs (transcutaneous electrical nerve stimulation)

psychological techniques (slow breathing, hypnosis, progressive muscle relaxation, guided imagery, cognitive therapy, behavioural therapy with systematic desensitization, massage, meditation)

aromatherapy (not very effective)

FS:
- Ginger
- Diet
- Aromatherapy
- CBT and psych
- TENS

Question 17

List four predictors of NV in a patient with advanced cancer

Answer 17

female gender

Age < 65

opioid medication

GI symptoms (tumor or obstruction)

gynaecological, stomach, esophageal, and breast cancers

the presence of metastases in the lung, pleura, peritoneum

Question 18

List five causes of delayed gastric emptying that can cause NV

Answer 18

◆ Anticholinergic drugs, opioids
◆ Ascites
◆ Hepatomegaly
◆ Peptic ulcer
◆ Gastritis
◆ Autonomic failure
◆ Diabetes

FS
- impaired motility: diabetes, drugs, auto failure
- stomach: gastritis, ulcer
- external pressure: hepatomegaly, ascites

Question 19

List 3 causes of nausea that can arise from the oropharynx*

Answer 19

sticky sputum
candida
mucosal lesions of CMV, HSV (AIDS)

Question 20

You have a patient who experiences attacks of worry and fear that lead to nausea and vomiting. What type of emesis is this? What are three possible treatments? (table 10.2.2)

Answer 20

anxiety induced emesis

possible treatments
◆ Address the anxiety
◆ Psychological and behavioural techniques
◆ Relaxation
◆ Benzodiazepines, anxiolytic antidepressant
◆ Broad spectrum anti-emetic

Question 21

What are four predictors for developing anticipatory nausea

Answer 21

female sex

young age

high levels of anxiety, distress

limited ability to cope

a history of alcoholism

experience of strange tastes during chemo

Question 22

How can you minimize risk of developing anticipatory nausea

Answer 22

good control of NV on first cycle of chemo

Question 23

What is the mechanism of corticosteroids as an antiemetic

Answer 23

Enhance antiemetic tone - reduce BBB permeability to noxious chemicals

enhance efficacy of other antiemetics

Question 24

List two drugs that do not cross BBB

Answer 24

Domperidone
buscopan

Question 25

Where is the chemoreceptor trigger zone? What is CTZ also known as?

Answer 25

AKA “Area postrema”
Floor of 4th ventricle where there is no BBB
Medulla oblangata in brainstem, next to NTS

Question 26

3 ways to treat intractable N/V

Answer 26

Broad spectrum anti-emetic: olanzapine, levomepromazine

Manage pt expectations

NG tube

Surgical intervention - stent, venting tube

Question 27

Anticipatory and anxiety NV causes nausea through which pathway?

Answer 27

Cerebral cortex -> NTS

Question 28

How does chemo cause nausea? Name 3 ways

Answer 28

Early (acute CINV within 24h): serotonin release in gut

Late (delayed CINV after 24h): substance P (binds to NK1 receptor)

Anticipatory nausea and anxiety

Question 29

How does opioid cause nausea? 4 ways

Answer 29

Constipation
Stimulation of GI mechanoreceptors -> NTS
Stimulation of CTZ (mu receptors are present in CTZ)
Increase vestibular sensitivity

FS:
- GI, CTZ, Vestibular, NTS