Anti emitics Flashcards
name a drug induced cause of vomiting presentation
Chemotherapy (Cisplatin) for lung cancer
Chemotherapy induced nausea & vomiting (CINV)
what cells does cisplatin damage in fundus
Cisplatin is toxic to enterochromaffin cells (ECs)
what are the consequences of this damage that trigger vomiting
ECs apoptose and release free radicals
excessive 5-HT is released
5-HT – activates 5-HT3A receptors
which locations are 5-HT3A receptors found
Nerve fibres to nucleus tractus solaris (NTS)
Nerves fibres to vomiting centre (VC) -DIRECT
Nerve fibres to chemoreceptor trigger zone (CTZ)
what location of the brain do these receptors reside in
Medulla oblongata (brainstem)
how exactly does the CTZ contribute
incomplete blood brain barrier (sense hormones etc.) - signals to VC (independent of VC)
what is the treatment for Chemotherapy induced nausea & vomiting (CINV)
Ondansteron - 5-HT3A receptor antagonist
what is it often coadmistered with (not essential)
Glucocorticoids - reduce free radical production
Arepepritant – neurokinin-1 receptor antagonist
what are 5-HT rc otherwise known as
serotonin receptors
simply what causes motion sickness
Auditory labyrinth - neural(sensory) mismatch
describe what areas the labyrinth projects to after this sensory mismatch
Vestibular system (via muscarinic (M) receptors)
Increased hypothalamic histamine (H) release
what do both these pathways affect which produces the effect of motion sickness
Vomiting centre
what receptors does the hypothalmic histamine act on
activates H1 receptors in CTZ
describe a separate pathway by which sensory mismatch in labyrinth travels
Vestibular system & hypothalamus may also activate the VC though cholinergic system (M1-5)
the hypothalamus affects the VC in 2 ways. describe them
via the CTZ (histamine release) which then sends input to VC
Directly via cholinergic stimulation)
is pharmacological therapy first line treatment for motion sickness
No
associated with drowsiness
how do drugs lessening affects of motion system act
H1 rc antagonist
or
non selective muscarinic rc antagonist
name these drugs and ther mechanisms
Promethazine - H1 receptor antagonist
Hyoscine (scopolomine) – non-selective muscarinic receptor antagonist
what is a cause of bloating and vomiting in T2DM
Gastroparesis – delayed emptying of the stomach
Reduced stomach contraction
besides the 5-HT rc pathway what other pathway is triggered in this condition
direct stimulation of the VC via dopamine D2 receptors
name a drug treatment for gastroparesis
Metoclopramide
Dopamine D2 receptor antagonist
state some additional MOAs that metoclopramide has
Prokinetic – stimulates gastric emptying
Inhibits D2 receptors in VC
5-HT3A receptor antagonist
Inhibits activation of CTZ
summarise the physiological control of vomiting
Vomiting centre (area postrema): innervated by the nucleus of the tractus solitarius
CTZ: communicates with the vomiting centre
summarise the Mechanistic triggers of vomiting
Cytotoxic drugs, motion sickness, gastrointestinal problems
what is side effect profile of motion sickness drugs
drowsiness
what is side effect profile of D2 rc antagonists
galactorrhea and extrapyramidal side effects
5-HT3A receptor antagonists side effects
constipation and headaches
