Describe the neural integration of vomiting. (60% of marks)
Describe the pharmacology of ondansetron. (40% of marks)
Candidates who failed the question did not answer the actual question. They did not discuss the neural integration but instead listed various inputs into the CTZ and vomiting centre. It was expected candidates could detail the pathways involved (afferent and efferent limbs) and describe the relationship with the coordinating centres. For example, afferent pathways to the vomiting centre include stretch and chemoreceptors located throughout the GIT via vagal and sympathetic nerves, pharyngeal touch receptors via glossopharyngeal nerves etc. Again structuring pharmacology answers was often poor.
Neurology of nausea and vomiting:
Pharmacology of ondansetron:
|Class||5-HT3 receptor antagonist|
|Routes of administration||Oral, IV, IM, s/c, sublingual|
|Absorption||Rapidly and completely absorbed, bioavailability ~ 60%|
|Solubility||pKa 7.4, sparingly soluble in water|
|Distribution||VOD= 2.5L/kg, 70-76% protein bound|
|Target receptor||5-HT3 serotonin receptor antagonist - which are ligand-gated cation channels and which mainly conduct depolarising sodium and potassium currents|
|Metabolism||95% of the dose is cleared by hepatic oxidative metabolism|
|Elimination||Clearance is almost completely hepatic; only some minimal amount is eliminated by the kidneys|
|Time course of action||Half life is about 3.8 hours; duration of effect is about 4-8 hours|
|Mechanism of action||Main mechanism of antiemetic activity is the antagonism of 5-HT3 ligand-gated cation channels at the chemoreceptor trigger zone. No anticholinergic or antidopaminergic effects, and therefore no effects on gastric motility or nausea related to vertigo|
|Clinical effects||- Antiemetic effects
- QT prolongation
- Headache, potentiation of migraine
|Single best reference for further information||Naylor et al, 1992|
Horn, Charles C. "The physiology of vomiting." Nausea and Vomiting. Springer, Cham, 2017. 15-25.
Parkes J.D. (1986) A Neurologist’s View of Nausea and Vomiting. In: Davis C.J., Lake-Bakaar G.V., Grahame-Smith D.G. (eds) Nausea and Vomiting: Mechanisms and Treatment. Advances in Applied Neurological Sciences, vol 3. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-70479-6_12
Markham, Anthony, and Eugene M. Sorkin. "Ondansetron." Drugs 45.6 (1993): 931-952.