Anti-emetics Flashcards
List the main mechanistic triggers of vomiting
Cytotoxic drugs (=CISPLATIN), motion sickness, gastrointestinal problems
Outline the physiological control of vomiting
Vomiting centre (area postrema): innervated by the nucleus of the tractus solitarius
Chemoreceptor Trigger Zone: communicates with the vomiting centre
How can chemotherapy cause vomiting
Cisplatin toxic to enterochromaffin cells (mainly in fundus), leading to apoptosis
Apoptosis causes release of free radicals and damage causes serotonin release
Free radicals lead to inflammation and vomiting
Seratonin released too
State the neural pathways by which vomiting can be induced in chemotherapy
5-HT3A receptors are bound by serotonin
Leading to activation of 5HT receptors on:
1, Nerve fibres to the NTS. This then leads to activation of VC
- Nerve fibres to the VC
- Nerve fibres to chemoreceptor trigger zone (distinct from the area postrema)
Note that NTS, VC and CTZ are all in the brainstem in the medulla
(I think this means vagal afferents activated which then go to these areas)
Where is the NTS found
Mostly in the medulla oblongata
(GVA and SVA)
Solitary nucleus is only nucleus in this column
TASTE (chorda tympani, glossopharyngeal and vagus)
GVA:
1. Mechano/chemoceptors on the vasculature (CNIX for carotid bodies, CNX for aortic bodies and SAN)
- Mechano/chemoceptors for heart, lungs, airways GI, pharynx via CN IX and X
The vagus carries GVA back to NTS
Which brain area involved in vomiting has an incomplete BBB
The CTZ (note that the CTZ is within the area postrema, but does not itself initiate vomiting. The area postrema, incl. CTZ, is a circumventricular organ)
When activated, the CTZ does not initiate vomiting itself, but relays stimuli to the integrative vomiting centre which produces the actual act of emesis.
How can nausea in chemotherapy patients be prevented
Ondansetron- 5-HT3A receptor antagonist
In addition to 5-HT3A receptor antagonists, what else can be given for chemo patients experiencing vomiting
Glucocorticoids to reduce free radical production by the EC cells (leading to inflammation)
Arepepritant (neurokinin-1 receptor antagonist BLOCKS connection from the NTS to the VC)
Outline the connection between the NTS and the VC
NK-1 receptors on the neurons projecting from NTS to VS
Blocked with arepepritant
Outline how motion sickness can lead to vomiting
Auditory labyrinth - neural mismatch so projections to vestibular system (via muscarinic receptors M1-M5, mainly M1)
Projection from vestibular system to the CTZ via hypothalamus releasing histamine. Acts on H1 receptors on the CTZ
Also direct connection from vestibular system to the VC via muscarinic receptors receptors
Drugs used in the treatment of motion sickness. Where do they act
- Promethazine is a H1 receptor antagonist (acts at the CTZ)
- Hyoscine is a non-selective muscarinic receptor antagonist (acts at vestibular system and at the VC)
What is gastroparesis
Delayed emptying of the stomach occurring in T2DM
Reduced stomach contraction
What causes vomiting in gastroparesis
MORE TO DO WITH D2 receptors. It’s not because of 5-HT or oxygen free radical production like it was in chemotherapy
5HT recpetors activated on neurons leadingto the CTZ and the VC
In this case, the nerves from the stomach are releasing dopamine onto the VC
Outline the drug treamtnet for gastropatesis
Metoclopramide
How does metoclopramide work
Dopamine D2 receptor antagonist
- prokinetic, stimulates gastric emptying AND
- inhibits D2 receptors in VC)
5-HT3A receptor antagonist
(inhibits activation of CTZ)
