Anti-emetics Flashcards
describe the vomiting pathway
- deep breath, glottis closes, larynx rises to open upper oesophageal sphincter
- soft palate elevates
- diaphrgam contracts sharply to create -ve intrathoracic pressure
- facilitates sphincter opening
- abdo walls contract as well to squeeze stomach and raise intra-gastric pressure
- pylorus closed
- upper sphincters opens
- pressure escapes proximally
what does cisplatin do? which cells particularly associated with nausea?
- kills quickly replicating cells
- has impact on enterochromaffin cells
- these cell apoptose
what happens when these cells apoptose?
- release excessive 5-HT
- also release free radicals
What is the 5-HT3aR? where is it expressed?
- receptors of 5-HT
- expressed on loads of cells
- IMPORTANT:
- on nerve fibres to nucleus tractus solitarius
- on nerve fibres to vomiting centre
- on nerve fibres to CTZ
describe the location of the CTZ and its significance
- CTZ closely associated to VC on brainstem
- outside of BBB so can detect signals in blood
- detect signals outside BBB and send it into VC
what is the treatment of chemo-induced nausea?
- ondansetron (5HT3A receptor antagonist)
- blocks signals and so reduces nausea and vomiting by chemo
what should ondansetron be coadministered with?
- glucocorticoid: reduce free radical production
- aprepitant: neurokinin-1 receptor antagonist (reduce free radicals)
where does motion sickness originate?
- labyrinthe
- neural mismatch
- labyrinthe projects to vestibular system via muscarinic receptors
how is the hypothalamus involved in motion sickness pathway?
- labyrinthe somehow connected to hypothalamus
- in hypothalamus, get inc. hypothalamic histamine release (H)
- activated H1 receptors in CTZ
how do the vestibular system and hypothalamus activate VC?
through cholinergic system
what is the treatment of motion sickness?
- promethazine: H receptor antagonist
- Hyoscine: non selective muscarinic receptor antagonist
what is gastroparesis?
- delayed emptying of stomach
- get vomiting due to unknown cause, abdo pain, bloating
- get reduced stomach contraction –> 5-HT
how does this trigger vomiting?
- direct fibres contact to vomiting centre
- 5HT activated 5-HT3a receptors on nerve fibres to VC
- activates these receptors to CTZ
- also get dopamine release which acts on D2 receptors on VC
how do you treat this nausea?
- metoclopramine
- 5HT3aR antagonist
what is the MoA of metoclopramine?
- dopamine D2 receptor antagonist
- stimulates gastric emptying
- inhibits D2 receptors in VC
