Question 2(p.2)

College Answer

Antiemetics can be classified by their receptor actions including, dopamine antagonists,serotonin antagonists, antihistamines, anticholinergics, antimotilinic etc or by their drug type – butyrophenones, phenothiazines, benzamides etc. Marks were divided between each class, and for “other/novel” antiemetics – such as, steroids, GABA agonists, alpha 2 agonists, mu receptor antagonists, canabinoids, propofol and NK1 receptor antagonists. Candidates were expected to mention the drug type, receptor interaction, the location of the receptors and the pathways inhibited by the drug – central CTZ, vestibular nuclei, solitary tract nucleus, vagal afferents or GIT motility and secretions. Most drugs work at one or more of these sites and marks were awarded for mention of this. Commonest errors were omission of adequate detail in each class. Antihistamines, anticholinergics and “others/novel” were frequently omitted. 

Syllabus - Q12e and Q2b2a
Reference: Chp 37 Goodman and Gillman

Discussion

• Dopamine (D2) antagonists:
  • Phenothiazines (promethazine), which also have potent activity against muscarinic, H1, 5-HT₃ and dopamine receptors
  • Butyrophenones (droperidol), which have slightly less potent anticholinergic and antihistamine effects 
  • Benzamides (metoclopramide), which have a prokinetic effect related to indirect cholinergic activity
• Anticholinergic (antimuscarinic): 
  • Hyoscine, atropine (purely antimuscarinic)
  • Phenothiazines and butyrophenones also have strong antimuscarinic effect
• 5-HT₃ antagonists: 
  • ondansetron and granisetron are pure, high-affinity 5-HT₃ antagonists
  • Phenothiazines and butyrophenones also have strong 5-HT₃ antagonist effects
• Antihistamines: 
  • Cyclizine and prochlorperazine have mainly anti-H1 effects
  • Most centrally acting H1 antagonists also have potent antimuscarinic activity
• NK-1 antagonists: 
  • aprepitant 
• Many miscellaneous agents:
  • dexamethasone
  • propofol
  • cannabinoids
  • benzodiazepines
  • pyridoxine (Vit B6)
• Main target receptors and neural pathways
  • Central processing of nausea
    • Nucleus of the solitary tract
    • Chemoreceptor trigger zone
    • Higher cortical areas
    • Vestibular apparatus
  • Neurotransmission in these centres is mediated by:
    • Muscarinic acetylcholine receptors
    • Dopamine receptors
    • 5-HT₃ serotonin receptors

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

Singh, Prashant, Sonia S. Yoon, and Braden Kuo. "Nausea: a review of pathophysiology and therapeutics." Therapeutic advances in gastroenterology 9.1 (2016): 98-112.