8.2 (10.2) Palliation of nausea and vomiting Flashcards
What are the 3 phases of emesis
Prodrome, retching, vomiting
What acts as a centre for integration of diverse stimuli (aka vomiting centre) and where is it located?
Nucleus Tractus Solitarius (NTS) located in dorsal medulla of the brainstem
List 4 main afferent sources for the vomiting centre/NTS in the human brain and the NTs associated with them
*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
List 3 main effector pathways from NTS
Cerebral cortex -> nausea
Endocrine (hypothalamus, pituitary gland) -> decrease appetite
Autonomic motor nuclei -> stomach -> vomiting
Fig. 8.2.1
List the major NTs that act on the CTZ
dopamine
serotonin 5HT3
neurokinin
List the major NTs that DIRECTLY act on the VC (NTS)
histamine
acetylcholine
serotonin (5HT3 and 5HT2)
Neurokinin 1
(No dopamine)
What are 2 dominant sites of NK 1 receptors responsible for emesis?
CTZ and NTS (both located in the medulla oblangata of brainstem)
What are the two approaches to the selection of an antiemetic for a patient with nausea? What is generally preferred and why?
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
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?
- Identify the likely cause(s) of nausea and/or vomiting
- Identify the pathway by which each cause triggers the vomiting reflex.
- Identify the neurotransmitter receptor involved in the identified pathway.
- Choose the most potent antagonist (i.e. anti-emetic) to the receptor identified
- Choose a route of administration that ensures that the drug reaches its site of action (usually not PO)
- Titrate the dose carefully, review the patient frequently.
- Give the antiemetic regularly.
- 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.
- If combining antiemetics, potential drug interactions need to be considered
List three classes of dopamine antagonists and give an example of each. Which is the most potent receptor blocker in the CTZ?
phenothiazines - prochlorperazine, methrotrimeprazine (note - broad spectrum)
butyrophenones - haloperidol - most potent receptor blocker or CTZ
benzamides - metoclopramide, domperidone
What are three side effects of low potency phenothiazines and which receptors are responsible for these side effects?
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.
List four examples of extrapyramidal symptoms that may occur from the use of dopamine antagonists
akathisia
acute dystonia
pseudoparkinsonism
tardive dyskinesia
What are three predominant indications for the use of 5HT3 receptor antagonists in the management of NV
chemotherapy induced NV
radiotherapy NV
post operative NV
List four common side effects of 5HT3 antagonists
Headache
dizziness
constipation
QTc prolongation
FS:
- GASH (uptodate) - GI, anxiety, sedation/dizzy, headache
- QTC
For what causes of nausea would you use the following drugs?
- corticosteroids
- cannabinoids
- benzo
- octreotide
- mirtazapine
- NK1 receptor antagonist
- 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
List 4 non pharm (alternative) techniques for NV
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
List four predictors of NV in a patient with advanced cancer
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
List five causes of delayed gastric emptying that can cause NV
◆ 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
List 3 causes of nausea that can arise from the oropharynx*
sticky sputum
candida
mucosal lesions of CMV, HSV (AIDS)
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)
anxiety induced emesis
possible treatments
◆ Address the anxiety
◆ Psychological and behavioural techniques
◆ Relaxation
◆ Benzodiazepines, anxiolytic antidepressant
◆ Broad spectrum anti-emetic
What are four predictors for developing anticipatory nausea
female sex
young age
high levels of anxiety, distress
limited ability to cope
a history of alcoholism
experience of strange tastes during chemo
How can you minimize risk of developing anticipatory nausea
good control of NV on first cycle of chemo
What is the mechanism of corticosteroids as an antiemetic
Enhance antiemetic tone - reduce BBB permeability to noxious chemicals
enhance efficacy of other antiemetics
List two drugs that do not cross BBB
Domperidone
buscopan
Where is the chemoreceptor trigger zone? What is CTZ also known as?
AKA “Area postrema”
Floor of 4th ventricle where there is no BBB
Medulla oblangata in brainstem, next to NTS
3 ways to treat intractable N/V
Broad spectrum anti-emetic: olanzapine, levomepromazine
Manage pt expectations
NG tube
Surgical intervention - stent, venting tube
Anticipatory and anxiety NV causes nausea through which pathway?
Cerebral cortex -> NTS
How does chemo cause nausea? Name 3 ways
Early (acute CINV within 24h): serotonin release in gut
Late (delayed CINV after 24h): substance P (binds to NK1 receptor)
Anticipatory nausea and anxiety
How does opioid cause nausea? 4 ways
Constipation
Stimulation of GI mechanoreceptors -> NTS
Stimulation of CTZ (mu receptors are present in CTZ)
Increase vestibular sensitivity
FS:
- GI, CTZ, Vestibular, NTS
