Antiemetics

Question 1

What is the mechanism of emesis?

Answer 1

Nausea, salivation and sweating 
Retrograde peristalsis (stomach and duodenum)
Deep inspiration
Glottis closes 
Abdominal muscles contract
LOS relaxes

Question 2

Where is the chemoreceptor trigger zone?

Answer 2

Medulla

Question 3

What triggers the CTZ?

Answer 3

Direct triggers
Visceral afferent from gut
Vestibular nuclei
Sensory afferents via midbrain

Question 4

What antiemetic agents work on the vestibular nuclei?

Answer 4

Muscarinic receptor antagonists

H1 receptor antagonists

Question 5

How do muscarinic receptor antagonists work?

Answer 5

Competitive blockade of muscarinic Ach receptors at the vestibular nuclei and CTZ

Question 6

Name the main muscarinic receptor antagonist

Answer 6

Hyoscine hydrobromide

Question 7

Muscarinic receptor antagonists are good for?

Answer 7

People who cant take tablets- also give sub/cut
Motion sickness
Bowel obstruction (also works on other muscarinic receptors)

Question 8

What are the side effects of hyoscine hydrobromide?

Answer 8

Sedation
Memory problems
Glaucoma
Dry mouth and constipation

Question 9

Name a H1 receptor antagonist

Answer 9

Cyclizine 
Promethazine 
Cinnirazine 
Diphenhydramine 
Levomepromazine

Question 10

How do H1 receptor antagonists work?

Answer 10

Acts on the vestibular nuclei, inhibiting histeminergic signals to the CTZ

Question 11

What are H1 receptor antagonists good for?

Answer 11

Motion sickness

Morning sickness - promethazine

Question 12

Cyclizine should not be given to which patients?

Answer 12

Children

Elderly

Question 13

What are the side effects of H1 receptor antagonists?

Answer 13

Sedation
Excitation
Cardiac toxicity - long QT interval
Antimuscarinic - dry mouth, constipation, urinary retention

Question 14

Which agents work on visceral afferents in the gut?

Answer 14

5HT3 receptor antagonists

D2 receptor antagonists

Question 15

How does serotonin act in the gut?

Answer 15

95% of serotonin in the body is within the gut, produced by enterochromaffin cells.
In response to parasympathetic stimulation, excites enteric neurones;
- smooth muscle to increase motility
- increase secretions
-regulate appetite

Question 16

How are serotonin receptor antagonists effective?

Answer 16

Reduce GI motility and secretions

Centrally they act to inhibit the CTZ

Question 17

What are the side effects of serotonin antagonists?

Answer 17

Constipation
Headache 
Elevated liver enzymes 
Long QT syndrome 
Extra-pyramidal effects

Question 18

Name a serotonin receptor antagonist

Answer 18

Ondansetron
Granesitron
Palonosetron

Question 19

What are the two D2 receptor antagonists?

Answer 19

Metoclopramide and domperidone

Question 20

How does metoclopramide work?

Answer 20

Increased ACh at muscarinic receptors in the gut, increases peristalsis.
Promotes gastric emptying by:
- increases tone at LOS
- increases tone and amplitude of gastric contractions
-decrease tone of pyloric

Question 21

What is D2 receptor antagonists good for?

Answer 21

GORD

Ileus

Question 22

What are the possible side effects of metoclopramide?

Answer 22

Galactorrhea via prolactin release

Extra-pyramidal effects

Question 23

What are the side effects of domperidone?

Answer 23

Sudden cardiac death - long QT and VT

Galactorrhoea

Question 24

What is the mechanism of domperidone?

Answer 24

Is similar to metoclopramide

Question 25

What is domperidone good for?

Answer 25

Improving lactation in breastfeeding mothers.

Question 26

What agents work on the CTZ?

Answer 26

``` 5HT3 receptor antagonists H1 receptor antagonists Muscarinic receptor antagonists D2 receptor antagonists Corticosteriods Cannabinoids NK1 receptor antagonists ```

Question 27

Name a cannabinoid and its mechanism of action

Answer 27

Nabilone -Act on the CTZ | Good for chemotherapy - last line

Question 28

What are the side effects of cannabinoids

Answer 28

Dizziness | Drowsiness

Question 29

Name some corticosteroids which work on the CTZ

Answer 29

Dexamethasone | Methylprednisolone

Question 30

What are corticosteriods good for and what are their side effects?

Answer 30

Perioperative N&V Chemotherapy Palliation Side effects: Insomnia, increased appetite and blood sugar. May have properties of D2 receptor antagonists

Question 31

Name a NK1 receptor antagonist

Answer 31

Aprepitant Fosaprepitant Netupitant

Question 32

How do NK1 receptor antagonists work?

Answer 32

Prevent action of substance P at CTZ and in peripheral nerves Boosts effects of 5HT3 receptor antagonists Anxiolytic and antidepressant properties. Good for chemotherapy - delayed emesis

Question 33

What are the side effects of NK1 receptor antagonists

Answer 33

- headache - diarrhoea/ constipation - Stevens-Johnson syndrome

Question 34

How do the D2 receptor antagonists work and name them?

Answer 34

Prochlorperazine Chlorpromazine Levomepromazine Haloperidol Act on the CTZ, may also block H1 and muscarinic receptors.

Question 35

What are the H1 receptor antagonists good for?

Answer 35

Motion sickness, vertigo | Prochlorperazine in pregnancy

Question 36

What are the side effects of D2 receptor antagonists?

Answer 36

Extra-pyramidal effects Sedation Hypotension

Question 37

What is haloperidol good for?

Answer 37

Chemotherapy and palliative care

Question 38

Domperidone ad metoclopramide can’t be used for?

Answer 38

Obstruction | Risk of perforation

Question 39

What is hyperemesis gravidarum and why is it dangerous?

Answer 39

Rapid rise in beta-HCG stimulate the CTZ, typically between 4-16 weeks. Higher risk with multiple pregnancies. Risk of dehydration, weight loss, electrolyte imbalance, urinary ketones.

Question 40

What is the drug pathway for treating hyperemesis gravidarum?

Answer 40

Promethazine/prochlorperazine Then metoclopramide Then ondansetron (risk of cleft lip/palate)

Question 41

What is the pathway for chemotherapy anti-emetic agents?

Answer 41

Low risk- dexamethasone Mod risk- dexamethasone + ondansetron High risk- dexamethasone +ondansetron + anprepitant For rescue, all use metoclopramide

Question 42

What are the post operative N&V risk factors?

Answer 42

Female Young Non-smoker History of PONV or motion sickness General anaesthetic Use of volatile gas or NO Po opioids Duration of surgery Laparoscopy

Question 43

What is the pathway for post operative anti-emetics?

Answer 43

Low risk- wait Med risk- 1 or 2 agents High risk - 2 agents