Antiemetics

Question 1

What is the indication for Serotonin 5-HT3 receptors (ondansetron; palonosetron)?

Answer 1

Acute Nausea & Vomiting.

This is because they primarily bind to serotonin 5-HT3 receptors in the GIT, to prevent nausea and vomiting triggered by the presence of drug within the GIT (rather than in the blood)

Question 2

How are serotonin 5-HT3 antagonists administered?

Answer 2

Oral or IV administration

Question 3

Describe the mechanism of actions of serotonin 5-HT3 antagonists (ondansetron)

Answer 3

Serotonin 5-HT3 antagonists -> blocks / inhibits serotonin 5-HT3 receptors
- peripherally at the gastrointestinal tract and peripheral nerve terminals
- centrally at the area postrema and chemoreceptor trigger zone in the nucleus at tractus solitarius
These results in inhibition of vagus nerve stimulation -> peripheral and central antiemetic effect

Question 4

Name 2 other drugs that can be combined with serotonin 5-HT3 to enhance its effect.

Answer 4

1. Corticosteroids (Dexamethasone)

2. Neurokinin 1 receptor antagonists (aprepitant, fosaprepitant)

Question 5

When do you give serotonin 5-HT3 antagonist for acute nausea & vomiting?

Answer 5

BEFORE.

Acts as a prophylaxis for acute nasuea and vomiting

Question 6

What is the indication for neurokinin 1 antagonists (aprepitant; fosaprepitant)

Answer 6

Acute Nausea & Vomiting

Delayed Nausea & Vomiting

Question 7

Describe the mechanism of actions of NK1 (receptor for substance P) antagonists.

Answer 7

NK 1 antagonists -> blocks/inhibit NK1 receptors in the central postrema and chemoreceptor trigger zone in the nucleus at tractus solitarius -> central antiemetic effect

Additional inhibition of substance P-induced vomiting due to antagonism.

Question 8

How is aprepitant and fosaprepitant (prodrug of aprepitant) administered?

Answer 8

Aprepitant: oral administration
Fosaprepitant: IV administration

Question 9

What are some adverse side effects of NK1 receptor antagonists?

Answer 9

Fatigue, dizziness, diarrhoea, abdominal pain

Question 10

Any drug interaction with NK1 antagonists?

Answer 10

Aprepitant -> CYP34A inhibitor

Fosaprepitant -> CYP2D6 inhibitor

Question 11

Name a drug of dopamine 2 receptor antagonists.

Answer 11

Metoclopramide.

Question 12

What is the indication of metoclopramide / dopamine 2 receptor antagonists.

Answer 12

• Mild Acute Nausea & Vomiting

- High Non-AC Delayed Nausea & Vomiting (combined with DEX)

Question 13

Describe the mechanism of action of metoclopramide / dopamine 2 receptor antagonists.

Answer 13

Dopamine 2 receptor antagonists (Metoclopramide) -> blocks / inhibits D2 receptors at the area postrema and chemoreceptor trigger zone in the nucleus of tractus solitarius.

Additional cholinergic smooth muscle stimulation -> prokinetic effect

Question 14

Name 2 adverse side effects or major concerns for Metoclopramide.

Answer 14

Hyperprolactinemia

• Gynecomastia and impotence in men
• Galactorrhoea and menstrual disturbance in women

Extrapyramidal side effects:

• parkinsonism
• dystonia
• tardive dyskinesia
• akathasia

Question 15

Name a drug in muscarinic (M1) receptor antagonist used for nausea and vomiting.

Answer 15

Scopalamine (hyoscine)

Question 16

What is the indication for Scopalamine?

Answer 16

Vestibular-induced nausea & vomiting (e.g. motion sickness)

Question 17

Describe the mechanism of action of Scopalamine.

Answer 17

Scopalamine (M1 receptor antagonists) -> inhibits / blocks M1 receptors at the area postrema and vestibular apparatus -> vestibular anti-emetic effect

Question 18

How are Scopalamine administered?

Answer 18

Transdermal patch administration

Because oral administration often result in high incidence of adverse side effects.

Question 19

Describe the adverse side effects of Scopalamine.

Answer 19

Anti-cholinergic side effects

• Dry mouth
• Urinary retention
• Mydiasis (pupil dilation)
• Tachycardia
• Flushing

Question 20

Name one contraindication for Scopalamine.

Answer 20

Acute angle-closure glaucoma due to the anti-cholinergic properties.

Question 21

Name a drug of Histamine 1 Receptor Antagonist.

Answer 21

Diphenhydramine

Question 22

Describe the MOA of Diphenhydramine.

Answer 22

Diphenhydramine (Histamine 1 receptor antagonists) -> blocks / inhibits histamine 1 receptos in the area postrema and vestibular apparatus -> vestibular antiemetic effect

1st gen antihistamine also additionally blocks / inhibits muscarinic receptors

Question 23

Describe the major side effects of DIphenhydramine.

Answer 23

• Antihistamine effect: sedation, drowsiness (as 1st gen antihistamine crosses BBB)
• Anticholinergic effect:
  Dry mouth, urinary retention, mydriasis, tachycardia, flushing

Question 24

Name a drug of the class corticosteroids used for nausea and vomiting?

Answer 24

Dexamethasone

Mimics effects of glucocorticoids / cortisol but exact MOA for nausea and vomiting unknown

Question 25

Corticosteroids (e.g. dexamethasone) are often prescribed with which antiemetic to prevent acute and delayed vomiting?

Answer 25

Serotonin 5-HT3 antagonist As it increases the sensitivity of serotonin 5-HT3 receptors when combined

Question 26

What are the major adverse side effects of dexamethasone?

Answer 26

Short term use not much side effects Long term use can result in iatrogenic Cushing's syndrome

Question 27

What are benzodiazepines?

Answer 27

GABA (gamma-aminobutyric acid) agonists

Question 28

What is the indication for benzodiazepines used for nausea and vomiting?

Answer 28

Anticipatory nausea and vomiting Nausea and vomiting caused by anxiety

Question 29

Describe the MOA of benzodiazepines used as an antiemetics.

Answer 29

Benzodiazepines -> binds to allosteric site of GABA-alpha receptors -> increase chloride conductance -> anxiolytic

Question 30

What are the adverse side effects of benzodiazepines? What happen if there is an overdose?

Answer 30

Sedation Overdose -> respiratory depression

Question 31

Name an atypical antidepressant used for nausea and vomiting.

Answer 31

Olanzapine

Question 32

What is the usage of olanzapine (atypical antidepressant) for nausea and vomiting?

Answer 32

For the treatment of chemotherapy-induced nausea and vomiting

Question 33

Describe the mechanism of action of olanzapine.

Answer 33

They binds to and inhibits the following receptors: - Serotonin 5-HT3 - Dopamine D1-D4 (not just D2) - Muscarinic M1 - Histamine 1

Question 34

What is one adverse side effect of antipsychotics to take note of?

Answer 34

QT Interval prolongation