Anti-emetic and Anti-diarrhoeal Drugs

Question 1

List the common drugs used as anti-emetics (plus 1 anti-diarrhoeal)

Answer 1

• Muscarinic receptor antagonists
• H1 receptor antagonists
• 5HT3 (serotonin) receptor antagonists
• D2 receptor antagonist - Metoclopramide, Domperidone, the ‘zines’ and Halperidol
• Corticosteroids
• Cannabinoids
• Neurokinin 1 receptor antagonists
• Opioid receptor agonist

Question 2

List the following for: Muscarinic receptor antagonists

• Use
• Example drugs
• Drug class
• Mechanism of action
• Adverse effects

Answer 2

Anti-emetic, good for:

• People who can’t take tablets
• Motion sickness
• Bowel obstruction

Hyoscine hydrobromide

Muscarinic receptor antagonists

Act at the vestibular nuclei AND central trigger zone
- Competitive blockade of muscarinic ACh receptors

• Sedation
• Memory problems
• Glaucoma
• Dry mouth
• Constipation

Question 3

List the following for: H1 receptor antagonists

• Use
• Example drugs
• Drug class
• Mechanism of action
• Adverse effects
• Warnings / contraindications

Answer 3

Anti-emetic, good for:

• Motion sickness – long plane journeys
• Promethazine – morning sickness in pregnancy

Cyclizine
Levomepromazine
Cinnirazine
Promethazine Diphenhydramine

H1 receptor antagonists

Act at the vestibular nuclei
- Inhibits histaminergic signals from the vestibular system to the CTZ in medulla

• Sedation
• Excitation
• Antimuscarinic - dry mouth, constipation, urinary retention,
• Cardiac toxicity (long QT interval)
• Cyclizine – don’t use with little old ladies and children

Question 4

List the following for: 5HT3 (serotonin) receptor antagonists

• Use
• Example drugs
• Drug class
• Mechanism of action
• Adverse effects

Answer 4

Anti-emetic

Ondansetron
Granisetron
Palonosetron

5HT3 (serotonin) receptor antagonists

Act at the visceral afferents AND central trigger zone
Peripherally at visceral afferents:
- Reduce GI motility
- Reduce GI secretions
Centrally:
- Inhibits central trigger zone

Uncommon

• Constipation
• Headache
• Elevated liver enzymes
• Long QT syndrome
• Extra-pyramidal effects – dystonia and parkinsonism

Question 5

List the following for: D2 receptor antagonist - Metoclopramide

• Use
• Drug class
• Mechanism of action
• Adverse effects

Answer 5

Anti-emetic, good for:

• GORD
• Ileus

D2 receptor antagonist

• Increases Ach at muscarinic receptors in the gut
• Promotes gastric emptying
• Increased tone at lower oesophageal sphincters (closes)
• Increased tone and amplitude of gastric contractions
• Decreased tone of pylorus sphincter (opens)
• Increases peristalsis
• Galactorrhoea via prolactin release
• Extra-pyramidal effects – dystonia and parkinsonism

Question 6

List the following for: D2 receptor antagonist - Domperidone

• Use
• Drug class
• Mechanism of action
• Adverse effects
• Warnings / contraindications

Answer 6

Anti-emetic, good for:
- Improving lactation in breast feeding mothers

D2 receptor antagonist

• Increases Ach at muscarinic receptors in the gut
• Promotes gastric emptying
• Increased tone at lower oesophageal sphincters (closes)
• Increased tone and amplitude of gastric contractions
• Decreased tone of pylorus sphincter (opens)
• Increases peristalsis
• Galactorrhoea
• Sudden cardiac death (long QT and VT)
• Used to be used very frequently BUT new evidence and a few high profile cases showed an increased risk of significant cardiac side effect

Question 7

List the following for: D2 receptor antagonist - the ‘zines’ and Halperidol

• Use
• Example drugs
• Drug class
• Mechanism of action
• Adverse effects

Answer 7

Anti-emetic, good for:

• Motion sickness
• Vertigo
• Pregnancy (Prochlorperazine)
• Chemotherapy and palliation (Haloperidol)

Prochlorperazine
Chlorpromazine
Levomepromazine
Haloperidol

D2 receptor antagonists

• Act at the central trigger zone
• May also block H1 and Muscarinic receptors
• Extra-pyramidal effects – dystonia and parkinsonism
• Sedation
• Hypotension

Question 8

List the following for: Corticosteroids

• Use
• Example drugs
• Drug class
• Mechanism of action
• Adverse effects

Answer 8

Anti-emetic, good for:

• Perioperative nausea and vomiting
• Chemotherapy
• Palliation

Dexamethasone
Methylprednisolone

Corticosteroids

• Assumed to act at the central trigger zone
• May also have properties of D2 receptor
• Insomnia
• Increase appetite
• Increase blood sugar

Question 9

List the following for: Cannabinoids

• Use
• Example drugs
• Drug class
• Mechanism of action
• Adverse effects

Answer 9

Anti-emetic:
- Last line chemotherapy

Nabilone

Cannabinoids

• Assumed to act on the central trigger zone
• Dizziness
• Drowsiness

Question 10

List the following for: Neurokinin 1 receptor antagonists

• Use
• Example drugs
• Drug class
• Mechanism of action
• Adverse effects

Answer 10

Anti-emetic:
- Good for chemotherapy – particularly for delayed emesis

Aprepitant
Fosaprepitant
Netupitant

Neurokinin 1 receptor antagonists

• Prevent the action of substance P at CTZ and in peripheral nerves
• Boosts effects of 5HT3 receptor antagonists
• Anxiolytic and antidepressant properties
• Headache
• Diarrhoea or constipation
• Stevens-Johnson syndrome

Question 11

List the following for: Opioid receptor agonist

• Use
• Example drugs
• Drug class
• Mechanism of action
• Adverse effects

Answer 11

Anti-diarrhoeal

Loperamide
Codeine
Morphine

Neurokinin 1 receptor antagonists

Loperamide
- Specific to Mu receptors in the myenteric plexus
- Decreases tone of longitudinal and circular smooth muscle
- Reduces peristalsis but increases segmental contractions
- Decreases colonic mass movement by supressing gastrocolic reflex
Codeine and Morphine:
- Used most often if patients are also in pain

• Paralytic ileus
• Nausea and vomiting
• Sedation (codeine and morphine)
• Addiction (codeine and morphine)