19. Antiemetics Flashcards
What is vomiting?
Involuntary, forceful expulsion of gastric contents through the mouth
What is the mechanism for vomiting?
Vomiting Centre in Medulla signals to vomit:
- Nausea, salivation, sweating
- Retrograde peristalsis
- Deep inspiration
- Closure of glottis
- Abdominal muscles contract
- Lower oesophageal sphincter relaxes
What is the chemoreceptor trigger zone?
Contains receptors that detect emetic agents in the blood and relays that information to the vomiting centre which is responsible for inducing the vomiting reflex
Where is the chemoreceptor trigger zone located?
Dorsal surface of the medulla at the caudal end of the fourth ventricle in a region known as the area postrema
- outside the blood brain barrier
What can stimulate the CTZ? (4)
- sensory afferents via the midbrain
- vestibular nuclei
- visceral afferents from the gut (Vagus)
- direct triggers (e.g. drugs)
What drugs act on the vestibular nuclei?
- Muscarinic receptor Antagonists
- H1 receptor antagonists
Give examples of muscarinic receptor antagonist used to treat emesis. (2)
Hyoscine hydrobromide
How does Hyoscine hydrobromide work?
Competitive blockade of muscarinic acetylcholine receptors
• In the vestibular nuclei • Also at the CTZ
- block parasympathetic action
Who are Hyoscine hydrobromide good for?
- People who can’t take tablets (available as a patch)
- Motion sickness
- Bowel obstruction
What are the side effects of hyoscine hydrobromide?
- Sedation
- Memory problems
- Glaucoma
- Dry mouth and constipation
Give examples of H1 receptor antagonists used to treat emesis.
Cyclizine! Levomepromazine! Cinnirazine Promethazine Diphenhydramine
How do H1 receptor antagonists work?
Centrally
• Acts on the vestibular nuclei
• Inhibits histaminergic signals from the vestibular system to the CTZ in medulla
What is the association between vestibular nuclei and emesis?
The vestibular nuclei are a group of four small special sensory nuclei in the lower pons and upper medulla for the vestibular nerve component of the vestibulocochlear nerve. movement of sterocilia on semicircular canals can stimulate the vestibular nerve leading to emesis like in motion sickness
Who are H1 receptor antagonists good for?
Good for :
• Motion sickness - long plane journeys
• Promethazine - morning sickness in pregnancy
Who is cyclizine not good for?
Little old ladies and children - can get disorientated and confused
What are the side effects of H1 receptor antagonists?
- Sedation
- Excitation
- Antimuscarinic - dry mouth, constipation, urinary retention,
- Cardiac toxicity (long QT interval)
What drugs act on the visceral afferents from the gut?
- 5HT3 receptor Antagonists
- D2 receptor antagonists
Where is most the serotonin in the body located and what is it produced by here?
95% serotonin in the body is located in the gut
• Produced by the enterochromaffin cells
WHat is serotonin produced in response to in the gut?
In response to parasympathetic stimulation,
what is the action of serotonin?
serotonin excites enteric neurones
• Smooth muscle contraction increases motility (except in the stomach)
• Increases gut secretions
• Regulates appetite
Give examples of 5HT3 receptor Antagonists used to treat emesis
Ondansetron!
Granisetron
Palonosetron
What are the effects of 5HT3 receptor Antagonists?
Peripherally • Reduces GI motility • Reduces GI secretions Centrally • Acts to inhibit the CTZ
Who are 5HT3 receptor Antagonists good for?
Almost everyone - it’s often the 1st line treatment
What are the side effects of 5HT3 receptor Antagonists?
Side effects - uncommon • Constipation • Headache • Elevated liver enzymes • Long QT syndrome • Extra-pyramidal effects - dystonia, parkinsonism
Give examples of D2 receptor antagonists that act on visceral afferents of gut? (2)
Metoclopramide, Domperidone
What are the effects of metoclopramide?
• Increases acetylcholine at muscarinic receptors in the gut
Promotes gastric emptying:
• ↑ tone at lower oesophageal sphincter so it closes
• ↑ tone and amplitude of gastric contractions
• ↓ tone of pylorus so it opens
• Increases peristalsis
What is metoclopramide good for?
- GORD
* Ileus
What is ileus?
lack of peristalsis
What are the side effects of metoclopramide?
- Galactorrhoea via prolactin release
* Extra-pyramidal effects - dystonia, parkinsonism
What are the effects of domperidone?
• Similar mechanism as metoclopramide
not used as much - significant cardiac side effect
what are the side effects of domeperidone?
- Sudden cardiac death (long QT and VT)
* Galactorrhoea
what is domperidone good for?
Improving lactation in breastfeeding mothers
When should prokinetics not be used?
- bowel obstruction
- risk of perforation
What drugs act directly on the CTZ? (7)
- 5HT3 receptor antagonists
- H1 receptor antagonists
- Muscarinic receptor antagonists
- D2 receptor antagonists
- Corticosteroids
- Cannabinoids
- NK1 receptor antagonists
Give examples of D2 receptor antagonists that act directly on the CTZ. (4)
Prochlorperazine
Chlorpromazine !
Levomepromazine
Haloperidol !
what are The ‘zine’s good for?
Motionsickness,vertigo.
action of the The‘zine’s?
- Act on the CTZ
* May also block H1 and Muscarinic receptors
which of the zines is used in pregnancy?
Prochlorperazine
What is haloperidol used for?
Good for:-chemotherapy and palliation
What are the side effects of these D2 receptor antagonists?
• Extra-pyramidal effects - dystonia, parkinsonism • Sedation • hypotension
