Anti-emetics Flashcards
Summarise the physiological control of nausea/vomiting.
Vomiting centre (area postrema): innervated by the nucleus of the tractus solitarius. Chemoreceptor trigger zone: communicates with the vomiting centre.
Identify the main mechanistic triggers of nausea/vomiting.
Cytotoxic drugs (e.g. cisplatin as chemotherapy)
Motion sickness
Gastrointestinal problems, e.g. gastroparesis
Pregnancy
Identify the main classes of antiemetic drugs.
5-HT3A receptor antagonists
Histamine H1 receptor antagonists
Muscarinic receptor antagonists
Dopamine D2 receptor antagonists
Discuss the pathophysiology of chemotherapy induced nausea and vomiting (CINV).
Cisplatin is toxic to enterochromaffin cells (ECs)- release of free radicals.
Free radicals- excessive 5-HT release from stomach.
5-HT activates 5-HT3A receptors on: nerve fibres to nucleus tractus solitaris (NTS) which projects up to the vomiting centre; nerve fibres to vomiting centre (VC); nerve fibres to chemoreceptor trigger zone (CTZ).
What is used to treat chemotherapy induced nausea and vomiting (CINV)?
Ondansetron: 5-HT3A receptor antagonist- most effective way of blocking CINV.
Glucocorticoids: reduce free radical production (inflammatory mediators- GCs reduce inflammation).
Aprepitant: neurokinin-1 receptor antagonist.
Discuss the pathophysiology of motion sickness.
Auditory labyrinth- neural mismatch- vestibular system (via muscarinic receptors).
Increased hypothalamic histamine release- activates H1 receptors in CTZ.
Vestibular system and hypothalamus may also activate the VC through cholinergic system.
What is used to treat severe motion sickness?
Promethazine: H1 receptor antagonist.
Hyoscine: non-selective muscarinic receptor antagonist.
Discuss the pathophysiology of gastroparesis induced nausea and vomiting.
Gastroparesis- delayed emptying of the stomach.
Reduced stomach contraction.
5-HT activates 5-HT3A receptors on: nerve fibres to vomiting centre; nerve fibres to chemoreceptor trigger zone.
What is used to treat nausea and vomiting as a result of gastroparesis?
Metoclopramide (dopamine D2 receptor antagonist):
-prokinetic (stimulates gastric emptying)
-inhibits D2 receptors in vomiting centre
5-HT3A receptor antagonist: Inhibits activation of CTZ
What are the main side effects of 5-HT3A receptor antagonists?
Headaches and constipation
What is the main side effect of histamine H1 receptor antagonists?
Drowsiness
What are the main side effects of muscarinic receptor antagonists?
Dry mouth, drowsiness and constipation
What are the main side effects of dopamine D2 receptor antagonists?
Extrapyramidal side effects
