Antiemetics Flashcards
What is the indication for Serotonin 5-HT3 receptors (ondansetron; palonosetron)?
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)
How are serotonin 5-HT3 antagonists administered?
Oral or IV administration
Describe the mechanism of actions of serotonin 5-HT3 antagonists (ondansetron)
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
Name 2 other drugs that can be combined with serotonin 5-HT3 to enhance its effect.
- Corticosteroids (Dexamethasone)
2. Neurokinin 1 receptor antagonists (aprepitant, fosaprepitant)
When do you give serotonin 5-HT3 antagonist for acute nausea & vomiting?
BEFORE.
Acts as a prophylaxis for acute nasuea and vomiting
What is the indication for neurokinin 1 antagonists (aprepitant; fosaprepitant)
Acute Nausea & Vomiting
Delayed Nausea & Vomiting
Describe the mechanism of actions of NK1 (receptor for substance P) antagonists.
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.
How is aprepitant and fosaprepitant (prodrug of aprepitant) administered?
Aprepitant: oral administration
Fosaprepitant: IV administration
What are some adverse side effects of NK1 receptor antagonists?
Fatigue, dizziness, diarrhoea, abdominal pain
Any drug interaction with NK1 antagonists?
Aprepitant -> CYP34A inhibitor
Fosaprepitant -> CYP2D6 inhibitor
Name a drug of dopamine 2 receptor antagonists.
Metoclopramide.
What is the indication of metoclopramide / dopamine 2 receptor antagonists.
- Mild Acute Nausea & Vomiting
- High Non-AC Delayed Nausea & Vomiting (combined with DEX)
Describe the mechanism of action of metoclopramide / dopamine 2 receptor antagonists.
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
Name 2 adverse side effects or major concerns for Metoclopramide.
Hyperprolactinemia
- Gynecomastia and impotence in men
- Galactorrhoea and menstrual disturbance in women
Extrapyramidal side effects:
- parkinsonism
- dystonia
- tardive dyskinesia
- akathasia
Name a drug in muscarinic (M1) receptor antagonist used for nausea and vomiting.
Scopalamine (hyoscine)
What is the indication for Scopalamine?
Vestibular-induced nausea & vomiting (e.g. motion sickness)
Describe the mechanism of action of Scopalamine.
Scopalamine (M1 receptor antagonists) -> inhibits / blocks M1 receptors at the area postrema and vestibular apparatus -> vestibular anti-emetic effect
How are Scopalamine administered?
Transdermal patch administration
Because oral administration often result in high incidence of adverse side effects.
Describe the adverse side effects of Scopalamine.
Anti-cholinergic side effects
- Dry mouth
- Urinary retention
- Mydiasis (pupil dilation)
- Tachycardia
- Flushing
Name one contraindication for Scopalamine.
Acute angle-closure glaucoma due to the anti-cholinergic properties.
Name a drug of Histamine 1 Receptor Antagonist.
Diphenhydramine
Describe the MOA of Diphenhydramine.
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
Describe the major side effects of DIphenhydramine.
- Antihistamine effect: sedation, drowsiness (as 1st gen antihistamine crosses BBB)
- Anticholinergic effect:
Dry mouth, urinary retention, mydriasis, tachycardia, flushing
Name a drug of the class corticosteroids used for nausea and vomiting?
Dexamethasone
Mimics effects of glucocorticoids / cortisol but exact MOA for nausea and vomiting unknown
Corticosteroids (e.g. dexamethasone) are often prescribed with which antiemetic to prevent acute and delayed vomiting?
Serotonin 5-HT3 antagonist
As it increases the sensitivity of serotonin 5-HT3 receptors when combined
What are the major adverse side effects of dexamethasone?
Short term use not much side effects
Long term use can result in iatrogenic Cushing’s syndrome
What are benzodiazepines?
GABA (gamma-aminobutyric acid) agonists
What is the indication for benzodiazepines used for nausea and vomiting?
Anticipatory nausea and vomiting
Nausea and vomiting caused by anxiety
Describe the MOA of benzodiazepines used as an antiemetics.
Benzodiazepines -> binds to allosteric site of GABA-alpha receptors -> increase chloride conductance -> anxiolytic
What are the adverse side effects of benzodiazepines?
What happen if there is an overdose?
Sedation
Overdose -> respiratory depression
Name an atypical antidepressant used for nausea and vomiting.
Olanzapine
What is the usage of olanzapine (atypical antidepressant) for nausea and vomiting?
For the treatment of chemotherapy-induced nausea and vomiting
Describe the mechanism of action of olanzapine.
They binds to and inhibits the following receptors:
- Serotonin 5-HT3
- Dopamine D1-D4 (not just D2)
- Muscarinic M1
- Histamine 1
What is one adverse side effect of antipsychotics to take note of?
QT Interval prolongation
