Nausea & Vomiting:

Choosing Antiemetics
Dr. Robin Love
March 2015
1
Objectives
Learn a practical approach to
management of nausea and vomiting in
palliative care

Practical approach…but there is very

little science to back this up

2
 Theoretical Approach
1. Identify the cause
2. Identify the physiological pathway
3. Identify the neurotransmitter
4. Choose the most potent antagonist
5. Choose the best route of administration
6. Titrate the dose carefully, give the dose
regularly, review frequently
7. If symptoms persist, change or add
additional treatments
Oxford Textbook of Palliative Medicine 3
 Cerebral Chemoreceptor
High CNS Trigger Zone
Sights, Smells Toxic
Memories Ca Emetogenic
Infection
Radiation
Drugs
Chemotherapy
Vestibular Opioids
Digoxin, etc
Opioids Biochemical
Uremia
Cerebellar Tumor
Integrative Hypercalcemia
Vomiting
GI Tract
Centre (IVC) Vagal
Increased
Intracranial Press Distension
Over-eating
Primary or Gastric Stasis
Met. Tumor Extrinsic Press.
Obstruction
High, mid, low
Constipation
Chemical Irritants
M Downing Blood, drugs4
 Cerebral Chemoreceptor
High CNS Trigger Zone

GABA, D2, 5HT3

cannabinoids

Vestibular

Integrative
H1, Achm Vomiting GI Tract
Vagal
Centre (IVC)

D2, 5HT3,
Increased
Ach, H1,
Intracranial Press 5HT4 ,
5HT2, 5HT3
cannabinoid

5
 Cerebral Chemoreceptor
High CNS Trigger Zone
D2 Antagonist
Benzodiazepines Prochlorperazine
Cannabinoids, Haloperidol
Methotrimeprazine
Chlopromazine
Olanzapine

Metoclopromide
Vestibular 5HT3 Antagonist
Ondansetron
Integrative
H1 antagonist
Vomiting GI Tract
Dimenhydrinate Vagal
Methotrimeprazine Centre (IVC)
D2 Antagonist
Olanzapine
Gastrokinetics
Anticholinergic Anticholinergic Metoclopromide
Scopolamine Scopolamine Domeperidone
Atropine Phenothiazines
Increased Atropine
Methotrimeprazine
Intracranial Press H1 Antagonist 5HT4 Agonist
Dimenhydrinate Metoclopromide
Dexamethasone Methotrimeprazine 5HT3 Antagonist
Gravol 5HT2 Antagonist Ondansetron
Olanzapine Metoclopramide
methotrimeprazine Octreotide
? VP Shunt Methotrimeprazine
Dexamethasone
5HT3 Antagonist CB1
Ondansetron cannabinoids
M Downing (updated feb 2015) 6
 Cerebral Chemoreceptor
High CNS Trigger Zone
D2 Antagonist
Benzodiazepines Prochlorperazine
Cannabinoids Haloperidol
Methotrimeprazine
Chlopromazine
Olanzapine

Metoclopromide
Vestibular 5HT3 Antagonist
Ondansetron
Integrative
H1 antagonist
Vomiting GI Tract
Dimenhydrinate Vagal
Methotrimeprazine Centre (IVC)
D2 Antagonist
Olanzapine
Gastrokinetics
Anticholinergic Anticholinergic Metoclopromide
Scopolamine Scopolamine Domeperidone
Atropine Phenothiazines
Increased Atropine
Methotrimeprazine
Intracranial Press H1 Antagonist 5HT4 Agonist
Dimenhydrinate Metoclopromide
Dexamethasone Methotrimeprazine 5HT3 Antagonist
Gravol 5HT2 Antagonist Ondansetron
Olanzapine Metoclopramide
methotrimeprazine Octreotide
? VP Shunt Methotrimeprazine
Dexamethasone
5HT3 Antagonist CB1
Ondansetron cannabinoids
M Downing 7
Framework :
How do we organize our approach?
All textbooks are organized differently.

 Cause?
 Receptor? ( these are not consistent in different texts)
 Drug class?
 Site of action
 Chemical type
 “medical class” ie antipsychotic, prokinetic…
 Drug we are most familiar with?
 Random guess?
8
Practical

Syndrome or Best
Etiology Drug

9
Antiemetic Drugs
Wide variety
Several classes
Much more complex than Analgesics
Some drugs affect more than one
receptor
Some drugs act in more than one
location

10
Classes of Antiemetic Drugs:
1. Dopamine Antagonist
A. Antipsychotics
Drug Principal Action
 Haloperidol  CTZ
 Prochlorperazine CTZ

 Chlorpromazine CTZ / IVC ?



 Methotrimeprazine CTZ / IVC / Gut ?



 Olanzapine 5HT2 plus…



Haloperidol the drug of choice:

- most potent at CTZ, most specific Dopamine agent
- lower side effects
- available tablets, liquid, sc, iv, im
11
- use low doses 0.5 –2 mg q8h
Classes of Antiemetic Drugs:
1.Dopamine Antagonist
B. Prokinetic
Drug Principal Action
 Metoclopramide  CTZ / GI
 Domperidone  GI

Metoclopramide the drug of choice:

- multiple effects ( CTZ, D2 in Gut, 5HT3, 5HT4)
- acts centrally and peripherally
- tablets, liquid, sc, iv
- watch for akathisia
- doses 10-20 (..40) mg qid
12
Classes of Antiemetic Drugs:
2. H1 antihistamine
Drug
 Diphenhydramine
 Dimenhydrinate
 Promethazine
 Hydroxyzine
Drug of Choice?
- promethazine sc at lower doses
Principal Action
 VC, vestibular
 VC, vestibular
 UGI tract, VC
 UGI tract, VC
13
Classes of Antiemetic Drugs:
3. Anticholinergic
Drug Principal Action
 Scopolamine  Vestibular / Vomiting
(hyoscine) Center/GI tract
 glycopyrrolate  Periphery/ GI tract
 Hydroxyzine

Scopolamine available as transdermal

or sc, iv, im
Glycopyrrolate – less CNS side effects
14
Classes of Antiemetic Drugs:
4. Steroids
Drug Principal action
 Dexamethasone  ???????
 Prednisone
 Methylprednisolone

- Dexamethasone po, sc
- Mechanism of action is not clear

- Also often add this in for difficult nausea

15
Classes of Antiemetic Drugs:
5. Cannabinoids
Drugs Principal action
 Nabilone  VC
 Many new choices of  VC
cannabinoids

Role is unclear, but can be very helpful in some vomiting cases

Lots of receptors still to be sorted out

16
Classes of Antiemetic Drugs:
6. 5-HT3 antagonists.
Drug Principal action
 Ondansetron  UGI tract ? CNS
 Granisetron

Reduces gastric secretions

? Other effects
Constipating
17
Classes of Antiemetic Drugs:
7. Benzodiazepines
Drugs Principal action
 Lorazepam  adjunctive
 Midazolam

Little direct antiemetic effect,

but they reduce anxiety , akathisia
and anticipatory nausea

18
Classes of Antiemetic Drugs
8. miscellaneous
Drugs Principal action
 Octreotide  Antisecretory etc
 Omeprazole  Proton pump inhibitor
 Ranitidine  H2 receptor antagonist
 Antacids

 Propofol  ? CTZ or VC

19
Non Drug Measures
Nasogastric tube
Gastrostomy tube ( venting)

20
Family and Nursing measures
Food type
Odors
Present small portions only of what they
want
“Palliative Diet” – eat what they feel like
eating
Educate patient and family about futility
of pushing calories
21
Common Syndromes of
Nausea

22
 1. Chemically Induced
 Causes  Treatment
 Opioids  Haloperidol
 Digoxin  Prochlorperazine
 Cancer treatment  Chlorpromazine
 Anticonvulsants  Methotrimeprazine
 Antibiotics  Metoclopramide
 Toxins ( tumor products,  Dexamethasone
ischemic bowel)  Lorazepam
 Metabolic ( Ca , liver or  Ondansetron
renal failure …)

23
2. Motion Induced
 Causes  Treatment
 Opioids  Promethazine
 Gastroparesis (phenergan)
 CNS tumor or  Dimenhydrinate
metastases (gravol)
 Scopolamine/Hyoscin
e
 Methotrimeprazine
 Doxylamine/pyridoxi
ne (Diclectin)

24
3. Gastric Stasis
 Causes  Treatment
 Opioids  Prokinetics
 Anticholinergic drugs  Metoclopramide
 Ascites  Domperidone
 Autonomic  Dopamine antag.
dysfunction  Haloperidol etc.
 Hepatomegaly  Reduce secretions
 Gastritis  scopolamine
 Obstruction/  Octreotide
 Omeprazole etc
mechanical

25
4.Vagal Induced
- stretch/distortion of viscera
 Causes  Treatment
 Constipation  Prokinetics
 Obstruction  Metoclopramide
 Mesenteric  Domperidone
metastases  Methotrimeprazine
 Liver metastases  Dimenhydrinate
 Ureteric obstruction  Scopolamine

26
5. Increased Intracranial
Pressure
 Causes  Treatment
 Tumor  Dexamethasone
 Edema  Dimenhydrinate
 Intracranial bleed  Methotrimeprazine
 lorazepam
 Infection ( Aids)

27
General Strategy
( if no obvious cause)
“ do you feel full and bloated like you
ate too much or is it more of a queasy
car sick kind of feeling ?”

metoclopramide

haloperidol

28
General Strategy
( if no obvious cause)
1. Metoclopramide 10-20 mg sc q 6h
2. +/ - Haloperidol 0.5-1 –2 mg sc q6h
3. + Antihistamine
4. + Dexamethasone
5. + Scopolamine
6. 3rd line including ondansetron, nabilone,
diclectin ….

29
Intractable Nausea
May require sedation
 Lorazepam, midazolam, chlorpromazine,
methotrimeprazine, etc.
 Propofol may be effective but not
practically available
Gastrostomy venting tube

30
Pearls
Optimize the dose depending on side effects
Re-evaluate possible cause
Add 2nd line that targets a different receptor
(usually add drugs, don’t just substitute as there
may be additive effects)
Continuous medication may be more
effective
May need multiple drug combinations in high
doses
Don’t forget the practical measures (reduce
intake etc.) 31