Question 23

College Answer

Antiemetics, as a topic has been frequently asked, in various formats in the past. Candidates who performed well had a good depth and breadth of knowledge as well as sufficient integration of knowledge to be able to classify and understand the basis to the various classifications. Essentially it was expected that candidates mention the classifications of Anticholinergics, Antihistamines, Anti 5HT, Antidopaminergics (benzamides, butyrophenones, phenothiazines), Steroids and other agents with known antiemetic activity (e.g. propofol, benzodiazepines, etc). In relation to metoclopramide it was expected that candidates would mention that it lowers pressure threshold for occurrence of intestinal peristaltic reflex, reduces intestinal muscle fatigue, enhances frequency and amplitude of longitudinal muscle contraction, coordinates gastric, pyloric and duodenal activity to improve GI motility, mechanism of action appears to depend on intramural cholinergic neuron, acts primarily by augmenting release of ACh and perhaps by inhibition of 5-HT release, increases lower oesophageal sphincter pressure, relaxes the pyloric sphincter and antagonize the inhibitory neurotransmitter, dopamine.

Discussion

Classification of antiemetics:

• Dopamine (D2) antagonists:
  • Phenothiazines (promethazine)
  • Butyrophenones (droperidol)
  • Benzamides (metoclopramide)
• Anticholinergic (antimuscarinic): 
  • Hyoscine, atropine (purely antimuscarinic)
• 5-HT₃ antagonists: 
  • ondansetron and granisetron
• Antihistamines: 
  • Cyclizine and prochlorperazine
• NK-1 antagonists: 
  • aprepitant 
• Many miscellaneous agents:
  • dexamethasone
  • propofol
  • cannabinoids
  • benzodiazepines
  • pyridoxine (Vit B6)

Gastrointestinal effects of metoclopramide:

• Oesophageal effects:
  • Increased amplitude of oesophageal perstaltic contractions (though not every study is able to demonstrate this effect)
  • Increased resting tone of the lower gastro-oesophageal sphincter (a short-term effect, lasting approximately one hour)
• Gastric effects:
  • Accelerates gastric emptying, including the scenarios of diabetic and post-operative gastroparesis - this is described by the college as "appears to depend on intramural cholinergic neuron". In actual fact it appears to be an indirect effect, where metoclopramide enhances the acetylcholine release from suitable nerve endings (Sanger, 1985)
  • Increased antral contractions
  • Improved "antroduodenal coordination" (Lee & Kuo, 2010)
• Intestinal effects
  • Increases the peristaltic activity of the upper small intestine

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.