20) Anti-Emetics

Question 1

State the 5 major classes of anti-emetic drugs.

Answer 1

Mixed receptor antagonists  
Dopamine (D2) receptor antagonists  
Muscarinic receptor antagonists  
Serotonin (5-HT3) receptor antagonists  
Cannabinoids

Question 2

What is nausea and vomiting often preceded by?

Answer 2

Sweating, salivation and an increase in heart rate

Question 3

Describe the process of vomiting.

Answer 3

Stomach, oesophagus and associated sphincters are relaxed
Contraction of upper small intestine, pyloric sphincter and pyloric region of stomach
Contents of upper jejunum, duodenum and pyloric region of stomach move to the body and fundus of the stomach
Lower and upper oesophageal sphincters and oesophagus relaxes
Retching/vomiting may occur

Question 4

What are the consequences of severe vomiting?

Answer 4

Dehydration
Hypochloraemic metabolic alkalosis
Contributes to reduction in bicarbonate excretion and increase in bicarbonate reabsorption
Increase in sodium reabsorption and increase in potassium excretion (hypokalaemia)

Question 5

What types of receptors in the stomach transmit signals to the vomiting centre and chemoreceptor trigger zone?

Answer 5

Chemoreceptors and Mechanoreceptors

Question 6

What is special about the location of the CTZ and vomiting centre?

Answer 6

It is located in a part of the brain that has a very porous blood brain barrier
So the CTZ and vomiting centre act as an early warning system to protect the brain from toxin damage

Question 7

Promethazine

Answer 7

mixed receptor antagonist.

Question 8

Describe the mode of action of this drug.

Answer 8

It is a competitive antagonist for the following receptors:
 Histaminergic
 Muscarinic
 Dopaminergic
Order of potency of antagonist activity: H > M > D

Question 9

What are the uses of promethazine / MRA ?

Answer 9

Motion sickness 
Disorders of the labyrinth 
Hyperemesis gravidarium 
Pre and post-operatively  
Relief of allergic symptoms, anaphylactic emergency, night sedation; insomnia

Question 10

What are the unwanted effects of promethazine?

Answer 10

Dizziness 
Tinnitus  
Fatigue 
Sedation  
Convulsions

Question 11

Metoclopramide

Domperidone

Answer 11

dopamine receptor antagonists.

Question 12

Describe the order of agonist potency of these drugs.

Answer 12

D > H > M

Question 13

What effect do Dop-recep-antag drugs have on the GI tract?

Answer 13

They have PROKINETIC effects on the GI tract:
 Increase smooth muscle motility
 Accelerate gastric emptying
 Accelerate the transit time of intestinal contents

Question 14

Why are these drugs poor at treating motion sickness?

Answer 14

The vestibular system has connections to the CTZ and it has direct connections to the vomiting centre
The dopamine antagonists block dopamine receptors in the CTZ but they are not blocking the rest of the signals that are going directly from the vestibular system to the vomiting centre

Question 15

State some uses of metoclopramide and domperidone // Dopamine Receptor Antagonists

Answer 15

Uraemia (severe renal failure)
Radiation sickness
GI disorders
Cancer chemotherapy

Question 16

metoclopramide versus domperidone

Answer 16

Metoclopramide crosses the BBB + gives CNS SEs

both Dop. Rec. Antag.

Question 17

Why must care be given over the bioavailability of co-administered drugs when patients are on dopamine receptor antagonists?

Answer 17

These drugs have prokinetic effects on the GI tract hence they accelerate the transit through the GI tract – this may mean that some drugs are not sufficiently absorbed in the GI tract e.g. digoxin

Question 18

What are some unwanted effects of metoclopramide and domperidone?

Answer 18

CNS side effects only with metoclopramide: 
 Drowsiness 
 Dizziness 
 Anxiety 
 Extrapyramidal reactions (Parkinsonian like syndrome – children more susceptible)
Endocrine side effects: 
 Hyperprolactinaemia 
 Galactorrhoea
 Disorders of menstruation

Question 19

Hyoscine

Answer 19

muscarinic receptor antagonist.

Question 20

What is the mode of action of muscarinic receptor antagonists?

Answer 20

Act centrally on the CTZ, vestibular nuclei and vomiting centre to block the activation of the vomiting centre

Question 21

What is hyoscine used for?

Answer 21

Prevention of MOTION SICKNESS

Sometimes used in operative pre-medication

Question 22

What are the unwanted effects of hyoscine?

Answer 22

Drowsiness 
Dry mouth  
Cycloplegia  
Mydriasis  
Constipation

Question 23

Ondansetron

Answer 23

serotonin receptor antagonist.

Question 24

What is the mode of action of serotonin receptor antagonists?

Answer 24

block transmission in visceral afferents + CTZ

Question 25

What is the main use of serotonin receptor antagonists as an anti-emetic?

Answer 25

MAIN USE: preventing anti-cancer drug induced vomiting (especially cisplatin)
Also used for radiotherapy induced sickness and post-operative nausea and vomiting

Question 26

What are the unwanted effects of ondansetron?

Answer 26

Headache
Sensation of flushing and warmth
Constipation

Question 27

Explain the use of combined ondansetron therapy with glucocorticoids.

Answer 27

Corticosteroids can be used in combination with ondansetron to treat moderate to high emetogenic chemotherapy
The improved efficacy of the combined treatment may be due to the anti-inflammatory properties of corticosteroids