30: Anti- Emetics Flashcards
What are the mechanistic triggers that cause nausea and vomiting?
- Cytotoxic drugs
- motion sickness
- gastrointestinal problems
- other higher centers
How can chemotherapy induce nauea and vomiting?
Chemotherapeutica are cytotoxic and might cause
- release of free radicals from enterochromaffin cells
- Cause excessive Release of 5HT
- 5HT binds to 5HT-3A receptors on
- Chemoreceptor trigger zone
- Vominting Centre (VZ)
- Nucleus tractus solaris (NTS) (triggers CTZ)
- Induction of feeling of nause and vomiting
How would you treat chemotherapy induced nausea?
It is due to overstimmulation of 5HT-3A receptors on CTZ
- Ondansetron = 5HT-3A antagonist
- glucocorticoids to reduce release of free radicals
- Arepepritant – neurokinin-1 receptor antagonist (expressed on vominting centre and gets signals from higher centres of the brain)
What is the MOA and use of Ondansetron?
It is a 5HT-3A receptor antagonist –> reduces (chemotherapy induced) nausea and vomiting
Explain the pathophysiology of motion sickness
Neural mismatch between visual and sensory input
- activates histamine receptors on vestibular nucleus
- Vestibular nucleus activates muscarenic recepotrs on CTZ
- Leading to muscarenic activation of VC –> nausea
How can you treat motion sickenss?
- Promethazine - H1 receptor antagonist
- Hyoscine (scopolomine) – non-selective muscarinic receptor antagonist (centrally acting)
What is the MOA and use of Promethazine?
It is a H1 receptor antagonist
- inhibits histamine-mediated activation of vestibular nucleus in motion sickness
What is the MOA and use of Hyoscine?
It is a non-selective muscarenic receptor antagonsit
- Used in treatemnt of motion sickness
- inhibits muscarenic-mediated activation of Chemoreceptor Trigger zone and Vomiting Centre
Explain the Role of dopamine in Nausea and Vomiting
There are Dopamine D2 receptors on CTZ –> when activated might cause nausea and vomiting
Explain the MOA and use of Metoclopramide
Used: treatemtn of nausea and vomiting
Has a dual MOA
- Dopamine D2 receptor antagonist
- inhibits D2 receptors an CTZ
- inhibits activation of CTZ
- (+ enhances gastric emptying e.g. in gastoparesis)
- inhibits D2 receptors an CTZ
- 5HT-3A receptor antagonist
- Inhibits activation of CTZ
Which drug has the following MOA?
- Dopamine D2 receptor antagonist
- inhibits D2 receptors an CTZ
- inhibits activation of CTZ
- (+ enhances gastric emptying e.g. in gastoparesis)
- inhibits D2 receptors an CTZ
- 5HT-3A receptor antagonist
- Inhibits activation of CTZ
Metoclopramide
Summarise the physiological control of nausea and vomiting
Overall: very complex system with many inputs but broken down
- Chemoreceptor trigger zone recievs input from periphery (e.g. stomach) or higher brain centres (e.g. vestibular nucles)
- Causes activation of Vomiting Centre
- Leading to Nausea (and vomiting)
What are the main classes of anti-emetic drugs?
- 5HT-3A receptor antagonsits (Odansetron, (Metroclopramide))
- Dopamine D2 receptor antagonist (Metoclopramide)
- Centrally acting Muscarenic receptor antagonist (Hyoscine)
- Histamine H1 receptor antagonist (Promethazine)
What is the clinical use of Dopamine receptor antagonists as an anti-emetic?
Used in gastroparesis induced N&V (Metoclopramide)
What are the side-effect of a centrally acting muscarenic receptor antagonist?
E.g. Hyoscine
- dry mouth
- drowsiness
