Dopamine D2 R antagonists - antiemetic

• Name 3 examples of dopamine D2- receptor antagonists and the types

  1. Benzamides

  • Meto.clop.ramide
  • Dom.peridone

  2. Phenothiazines

  • Pro.chlorp.erazine
• What is the indication of dopamine D2- receptor antagonists

  • Prophylaxis/ treatment of Nausea and vomiting,

  — particularly REDUCED GUT MOTILITY
• What is the general pathways of nausea and vomiting

  • Triggered by drug irritation, motion, vestibular disorders and higher stimuli(sight, smells, emotions.)
  • Inputs sent from CTZ, vagus nerve, vestibular systems and higher centres
  • Act on ‘vomiting centre’ in the medulla
• D2 - receptor antagonist MOA

  1. D2 Main receptor in CTZ

  • Role = sense emetogenic substance (e.g. drugs) in blood
  • t/f inhibits CTZ stimulation + nausea/vomiting

  2. D2 NT in gut - promotes relaxation of stomach + lower oesophageal sphincter, inhibits gasproduodenal coordination

  • t/f have a prokinetic effect :) in reduced gut mobility (e.g opioids/ diabetic gastroparesis) emesis
  • ** particularly metoclopramide** - augmented with enteric 5-HT4 agonist activity
• Common s/e from dopamine D2- receptor antagonists

  Common s/e from dopamine D2- receptor antagonists

  A) Larger outside BBB

  B) QT interval prolongation, arrhythmias

  C) Extra pyramidal effect (abnormal movement)

  D) Antipsychotic MOA

  E) Drowsiness

  
• What warnings for the use of Dopamine D2- receptor antagonists

  What warnings for the use of Dopamine D2- receptor antagonists

  A) Benzamides

  B) Phenothiazines

  C) Safe in Parkinson’s

  D) Cautioned in Parkinson’s

  E) Cautioned in severe renal impairment

  F) Contraindicated in <12 years and <35kg

  G) Contraindicated in neonatal

  H) Cautioned in children and young adults

  I) Most prokinetic

  J) Cautioned in intestinal obstruction

  K) Contraindicated in Perforation

  
• Important interactions with dopamine D2- receptor antagonists


  Important interactions with dopamine D2- receptor antagonists

  A) Antipsychotic cautioned due to extrapyramidal s/e

  B) Drugs that prolong QT interval cautioned e.g SSRIs

  C) Severe interaction with dopaminergic agents

  D) Cautioned in drugs that inhibit CYP 450

  
• What are the doses and practical prescribing for dopamine D2- receptor antagonists 


  What are the doses and practical prescribing for dopamine D2- receptor antagonists

  A) 5-7 days

  B) 10mg

  C) 8

  D) IM, IV

  E) 3

  F) Gastroparesis

  G) Because better safety profile

  H) 2nd

  I) Drowsiness

  
• What is something you should monitor with dopamine D2- receptor antagonists


  • Prolonged use is not recommended
  • Monitor for extrapyramidal features (e.g increased tendency to fall)
• How are dopamine D2- receptor antagonists used in patients with - Chronic condition that slows stomach emptying

  • Requires LT prokinetic treatment
  • Metoclopramide = best prokinetic effect (has additional 5-HT4 agonist activity)
  • Given at lowest effective dose (5mg 8-hrly) to minimise exposure
  • Can be alternated with erythromycin (prokinetic)

  Clinical tip ;) trial treatment suspension: ‘drug holiday’ to see if it is still needed