1

Nausea & Vomiting:Choosing Antiemetics

Dr. Robin LoveMarch 2015

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

3

Theoretical Approach

1. Identify the cause2. Identify the physiological pathway3. Identify the neurotransmitter4. Choose the most potent antagonist5. Choose the best route of administration6. Titrate the dose carefully, give the dose

regularly, review frequently7. If symptoms persist, change or add

additional treatments

Oxford Textbook of Palliative Medicine

4

IntegrativeVomiting

Centre (IVC)

CerebralHigh CNS

Sights, SmellsMemories

ChemoreceptorTrigger Zone

ToxicCa EmetogenicInfectionRadiation

DrugsChemotherapyOpioidsDigoxin, etc

BiochemicalUremiaHypercalcemia

Vestibular

OpioidsCerebellar Tumor

IncreasedIntracranial Press

Primary orMet. Tumor

GI TractVagal

DistensionOver-eatingGastric StasisExtrinsic Press.

ObstructionHigh, mid, lowConstipation

Chemical IrritantsBlood, drugsM Downing

5

IntegrativeVomiting

Centre (IVC)

CerebralHigh CNS

ChemoreceptorTrigger Zone

Vestibular

IncreasedIntracranial Press

GI TractVagal

D2, 5HT3

D2, 5HT3,5HT4 ,

Ach, H1,5HT2, 5HT3cannabinoid

GABA,cannabinoids

H1, Achm

6

IntegrativeVomiting

Centre (IVC)

CerebralHigh CNS

ChemoreceptorTrigger Zone

Vestibular

IncreasedIntracranial Press

GI TractVagal

DexamethasoneGravolmethotrimeprazine? VP Shunt

D2 AntagonistProchlorperazineHaloperidolMethotrimeprazineChlopromazineOlanzapine

Metoclopromide5HT3 Antagonist

Ondansetron

D2 AntagonistGastrokinetics

MetoclopromideDomeperidone

PhenothiazinesMethotrimeprazine

5HT4 AgonistMetoclopromide

5HT3 AntagonistOndansetronMetoclopramide

OctreotideDexamethasoneCB1

cannabinoids

AnticholinergicScopolamineAtropine

H1 AntagonistDimenhydrinateMethotrimeprazine

5HT2 AntagonistOlanzapineMethotrimeprazine

5HT3 AntagonistOndansetron

BenzodiazepinesCannabinoids,

H1 antagonistDimenhydrinateMethotrimeprazineOlanzapine

AnticholinergicScopolamineAtropine

M Downing (updated feb 2015)

7

IntegrativeVomiting

Centre (IVC)

CerebralHigh CNS

ChemoreceptorTrigger Zone

Vestibular

IncreasedIntracranial Press

GI TractVagal

DexamethasoneGravolmethotrimeprazine? VP Shunt

D2 AntagonistProchlorperazineHaloperidolMethotrimeprazineChlopromazineOlanzapine

Metoclopromide5HT3 Antagonist

Ondansetron

D2 AntagonistGastrokinetics

MetoclopromideDomeperidone

PhenothiazinesMethotrimeprazine

5HT4 AgonistMetoclopromide

5HT3 AntagonistOndansetronMetoclopramide

OctreotideDexamethasoneCB1

cannabinoids

AnticholinergicScopolamineAtropine

H1 AntagonistDimenhydrinateMethotrimeprazine

5HT2 AntagonistOlanzapineMethotrimeprazine

5HT3 AntagonistOndansetron

BenzodiazepinesCannabinoids

H1 antagonistDimenhydrinateMethotrimeprazineOlanzapine

AnticholinergicScopolamineAtropine

M Downing

8

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?

9

Practical

Syndrome or Best Etiology Drug

10

Antiemetic Drugs

Wide variety Several classesMuch more complex than AnalgesicsSome drugs affect more than one

receptorSome drugs act in more than one

location

11

Classes of Antiemetic Drugs:1. Dopamine Antagonist

A. AntipsychoticsDrug Haloperidol Prochlorperazine Chlorpromazine Methotrimeprazine Olanzapine

Principal Action CTZ CTZ CTZ / IVC ? CTZ / IVC / Gut ? 5HT2 plus…

Haloperidol the drug of choice:- most potent at CTZ, most specific Dopamine agent - lower side effects- available tablets, liquid, sc, iv, im- use low doses 0.5 –2 mg q8h

12

Classes of Antiemetic Drugs:1.Dopamine Antagonist

B. ProkineticDrug Metoclopramide Domperidone

Principal Action CTZ / GI 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

13

Classes of Antiemetic Drugs:2. H1 antihistamine

Drug Diphenhydramine Dimenhydrinate Promethazine Hydroxyzine

Principal Action VC, vestibular VC, vestibular UGI tract, VC UGI tract, VC

Drug of Choice?- promethazine sc at lower doses

14

Classes of Antiemetic Drugs:3. Anticholinergic

Drug Scopolamine

(hyoscine) glycopyrrolate Hydroxyzine

Principal Action Vestibular / Vomiting

Center/GI tract Periphery/ GI tract

Scopolamine available as transdermalor sc, iv, imGlycopyrrolate – less CNS side effects

15

Classes of Antiemetic Drugs:4. Steroids

Drug Dexamethasone Prednisone Methylprednisolone

Principal action ???????

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

- Also often add this in for difficult nausea

16

Classes of Antiemetic Drugs:5. Cannabinoids

Drugs Nabilone Many new choices of

cannabinoids

Principal action VC VC

Role is unclear, but can be very helpful in some vomiting casesLots of receptors still to be sorted out

17

Classes of Antiemetic Drugs:6. 5-HT3 antagonists.

Drug Ondansetron Granisetron

Principal action UGI tract ? CNS

Reduces gastric secretions? Other effectsConstipating

18

Classes of Antiemetic Drugs:7. Benzodiazepines

Drugs Lorazepam Midazolam

Principal action adjunctive

Little direct antiemetic effect, but they reduce anxiety , akathisia and anticipatory nausea

19

Classes of Antiemetic Drugs8. miscellaneous

Drugs Octreotide Omeprazole Ranitidine Antacids

Propofol

Principal action Antisecretory etc Proton pump inhibitor H2 receptor antagonist

? CTZ or VC

20

Non Drug Measures

Nasogastric tubeGastrostomy tube ( venting)

Family and Nursing measures

Food typeOdorsPresent small portions only of what they want“Palliative Diet” – eat what they feel like eatingEducate patient and family about futility of pushing calories

21

22

Common Syndromes of Nausea

23

1. Chemically Induced

Causes Opioids Digoxin Cancer treatment Anticonvulsants Antibiotics Toxins ( tumor products,

ischemic bowel) Metabolic ( Ca , liver or

renal failure …)

Treatment Haloperidol Prochlorperazine ChlorpromazineMethotrimeprazineMetoclopramideDexamethasone LorazepamOndansetron

24

2. Motion Induced

Causes Opioids Gastroparesis CNS tumor or

metastases

Treatment Promethazine

(phenergan) Dimenhydrinate

(gravol) Scopolamine/Hyoscin

e Methotrimeprazine Doxylamine/pyridoxi

ne (Diclectin)

25

3. Gastric Stasis

Causes Opioids Anticholinergic drugs Ascites Autonomic

dysfunction Hepatomegaly Gastritis Obstruction/

mechanical

Treatment ProkineticsMetoclopramide Domperidone

Dopamine antag.Haloperidol etc.

Reduce secretions scopolamine Octreotide Omeprazole etc

26

4.Vagal Induced- stretch/distortion of visceraCauses

Constipation Obstruction Mesenteric

metastases Liver metastases Ureteric obstruction

Treatment ProkineticsMetoclopramide Domperidone

Methotrimeprazine Dimenhydrinate Scopolamine

27

5. Increased Intracranial Pressure

Causes Tumor Edema Intracranial bleed Infection ( Aids)

Treatment Dexamethasone

Dimenhydrinate Methotrimeprazine lorazepam

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 ?”

28

metoclopramide

haloperidol

29

General Strategy ( if no obvious cause)

1. Metoclopramide 10-20 mg sc q 6h 2. +/ - Haloperidol 0.5-1 –2 mg sc q6h3. + Antihistamine4. + Dexamethasone5. + Scopolamine6. 3rd line including ondansetron, nabilone,

diclectin ….

30

Intractable Nausea

May require sedation Lorazepam, midazolam, chlorpromazine,

methotrimeprazine, etc. Propofol may be effective but not

practically available

Gastrostomy venting tube

31

Pearls

Optimize the dose depending on side effectsRe-evaluate possible causeAdd 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 effectiveMay need multiple drug combinations in high dosesDon’t forget the practical measures (reduce intake etc.)