Question 23

College Answer

Successful candidates were those who discussed the multiple locations in the vomiting pathway where a drug acts, the receptors involved and discussed 5 or more classes. Several approaches can be taken to this topic. Classification by drug group works well and then allows more detail to be provided about possible receptor activity. 
For example:
Anithistamines: Promethazine H1 ++++ M ++ D2 ++ 5-HT3
Anitcholinergics: Scopalamine H1 + M ++++ D2 + 5-HT3
Benzamines: Metoclopromide H1 + M -- D2 +++ 5-HT3 ++, 
Neuroleptics: Droperidol H1 + M - D2 +++ 5-HT3 +, 
5-HT3 Antagonists: Ondansetron H1 - M - D2 - 5-HT3 ++++, Granisetron H1 ++++ M ++ D2 ++ 5-HT3 ;
Glucocorticoids: Dexamethasone H1 - M - D2 - 5-HT3 -,
Propofol: GABBA 
Cannabinoids: direct on vomiting center. 
An alternative approach involves a discussion of the distribution of receptor sites: nucleus vestibularis H1 M, area postrema (chemoreceptor trigger zone) 5-HT3 D2 M1 H1, nucleus tractus solitarius 5-HT3 D2 M H2 and then discuss which drugs act where. This material has  also been previously covered in the viva examination and knowledge of both drug properties and receptor distribution is often required. 
Few answers detailed relative activity at various receptors types – “+” scale illustrated above would be sufficient to convey an understanding to the examiners.

Discussion

It feels important to convey an understanding to the readers that "GABA" is the  agreed-upon conventional abbreviation of γ-aminobutyric acid, whereas "GABBA" is an iconic cricket stadium in Brisbane. Beyond spelling weirdness ("scopalamine"?), this table is outrageously inaccurate. For example, granisetron is definitely not a "++++" histamine receptor blocker. Moreover it is not clear what exactly "+" means here; does it reflect receptor affinity, or an agonist effect? It can't possibly be agonist effect, because "scopolamine" is definitely not a "++++" muscarinic agonist, except then what do we make of the "-" signs?

Here is a better, slightly more scientific table from Tomassino (2012), in case anybody still insists on using this system. It is sufficiently similar to all other such tables, in the sense that they are all different, and none of the source material for their data is referenced. At least this one explains what "-" means. 

An alternative classification could instead concentrate on the specific receptor effects, for example:

• 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)

Lyons, Samantha, and Ben Ballisat. "Antiemetic drugs: pharmacology and an
overview of their clinical use" Update in Anaesthesia 31 (2016).

Flake, Zachary A., Robert Scalley, and Austin G. Bailey. "Practical selection of antiemetics." American family physician 69.5 (2004): 1169-1174.

Sanger, Gareth J., and Paul LR Andrews. "A history of drug discovery for treatment of nausea and vomiting and the implications for future research." Frontiers in pharmacology 9 (2018): 913.