anti-emetics

see also:

• vomiting / emesis
• metoclopramide (Maxolon)
• ondansetron
• prochlorperazine (Stemetil)
• domperidone (Motilium)

• the brain stem “vomiting centre” is a loosely organised neuronal region within the lateral medullary reticular formation.
• high concentrations of muscarinic M1, histamine H1, neurokinin NK1 and serotonin 5-HT3 receptors have been detected in this region.

• the traditional anti-emetic, metoclopramide (Maxolon) primarily acts upon the CTZ via D2 antagonism and thus has limited role in Mx of vertigo, and potentially has significant dopamine related extrapyramidal adverse effects as well as prokinetic effects on the GIT.
• the new serotonin 5-HT3 anatagonists such as ondansetron and tropisetron have a much cleaner adverse effect profile as they do not have dopamine-related extrapyramidal reactions such as oculogyric crisis, dystonic reactions, akathisia, nor do they have significant GIT effects, although they may slow colonic transit. They are NOT well suited to Mx of motion sickness or vertigo. They work well for chemotherapy and post-operative nausea.
• anti-muscarinic anticholinergic agents and H1 antihistamines have weak anti-emetic actions but are useful for prevention or Rx of motion sickness.
• phenothiazines such as chlorpromazine (Largactil) and prochlorperazine (Stemetil) along with butyrophenone type antipsychotic agents such as droperidol (Droleptan) have significant antiemetic actions via D2 antagonism and antimuscarinic effects but have significant adverse effects such as sedation, hypotension and exptrapyramidal_reactions
• corticosteroids appear to enhance the anti-emetic effects of 5-HT3 antagonists in chemotherapy patients.
• new neurokinin NK-1 anatagonists such as aprepitant and fosaprepitant also enhance the anti-emetic actions of 5-HT3 antagonists in chemotherapy patients.
• benzodiazepines can be useful for reducing the psychologic component to nuasea and vomiting in some patients.
• cannabinoids have an anti-emetic effect for chemotherapy patients particulary in combination with phenothiazines but have autonomic adverse effects as well as possible sedation, dysphoria and hallucinations.

• motion sickness is an autonomic syndrome similar to that which accompanies vertigo, except that it is due to real motion and not an illusion of motion.
• prevention and Rx is usually best with medications which have anticholinergic activity

• Aust. Prescriber 2009 - preventing motion sickness in children (pdf)
• non-pharmacologic:
  • distraction - keep eyes on horizon where possible
  • avoid reading or playing games whilst traveling
  • avoid unnecssary head movements by using pillow as head rest
  • in a car try sitting towards the front
  • if flying, try sitting over the wing for better stability
  • in a boat, try to keep standing up with legs far apart and keep watching the horizon to help give your brain more stable inputs until it learns the new motions (this takes about 36hrs)
  • avoid heavy, greasy meals prior to travel
  • avoid overheating - allow adequate ventilation
  • keep calm - motion sickness tends to be worse with anxiety
  • ginger may help but no proof, and as it inhibits thromboxane synthetase, high doses may potentiate the effects of anticoagulants.
• pharmacologic:
  • dimenhydrinate
    • take orally 30min before travel
    • dose: child 2-7yrs: 12.5-25mg; 8-12yrs: 25-50mg; adults 50-100mg;
  • hyoscine hydrobromide:
    • as effective as antihistamines, less sedating but more anticholinergic effects
    • take orally 30min before travel
      • dose: child 2-7yrs: 75mcg; 8-12yrs: 150-300mcg; adults 300-600mcg;
    • transdermal patches are available overseas for those above 10yrs of age.
  • promethazine:
    • take orally 1-2 hours before travel
    • dose: child 2-5yrs: 5-6.25mg; 6-10yrs: 10-12.5mg; adults 25mg;
  • NB. non-sedating antihistamines, such as loratadine and cetirizine, penetrate poorly into the central nervous system and are not

effective against motion sickness.

• dimenhydrinate:
  • dose:
    • children: 1 to 1.5 mg/kg orally, 6-hourly, up to 175 mg in any 24-hour period
    • adults: 50 to 100 mg orally, 4- to 6-hourly, up to 400 mg in any 24-hour period
• hyoscine hydrobromide:
  • dose:
    • children: 6 to 8 micrograms/kg orally, 6-hourly, up to 600 micrograms in any 24-hour period
    • adults: 300 to 600 micrograms orally, 4- to 6-hourly, up to 1200 micrograms in any 24-hour period
• promethazine:
  • dose:
    • children: 0.125 to 0.3 mg/kg orally, 6-hourly, up to 100 mg in any 24-hour period
    • adults: 25 to 50 mg orally, then 25 mg orally, 8- to 12-hourly, up to 100 mg in any 24-hour period.

• see ED Mx of vertigo and BPV

• see gastroenteritis

• see hyperemesis gravidarum
• first line includes:
  • avoidance of food smells
  • pyridoxine (vitamin B6)
• second line includes:
  • metoclopramide (Maxolon)
• third line includes:
  • prochlorperazine (Stemetil)
  • ondansetron - but not approved on PBS for this use, thus expensive for outpatient use.

• regional anaesthesia
• propofol for induction and maintenance of anaesthesia
• supplementary oxygen
• hydration
• avoidance of nitrous oxide
• avoidance of volatile anaesthetics
• minimisation of intra- and postoperative opioid use
• minimisation of neostigmine dose (ie. avoid doses > 2.5mg)
• in high risk patients (eg. women non-smokers with PH motion sickness), consider:
  • dexamethasone 4-8mg (adults) prior to induction of anesthesia
  • low dose droperidol post-op, especially if using PCA - no more than 2.5mg droperidol with 100mg morphine in PCA infusion.
    • be aware of the warnings relating to prolonged QT and sudden death, although none have occurred at low dose for prevention of post-op nausea.
  • promethazine at the end of surgery is effective but causes sedation
  • iv cyclizine 25mg appears to decrease PONV by 55-65% but has the usual adverse effects of antihistamines (H1) including sedation and anticholinergic effects
  • NB. THERE IS NO EVIDENCE TO SUPPORT METOCLOPRAMIDE in 10mg IV doses is useful in preventing post-op nausea and vomiting.

• exclude medication and mechanical causes (eg. swallowing blood, abdominal obstruction)
• if using opioid via PCA, add droperidol as above
• ondansetron 4-8mg (25-100mcg/kg up to 4mg in children) slow iv (although studies have shown doses as low as 1mg in adults may be effective), can repeat dose after 6hrs
• if ongoing vomiting, use a different class agent:
  • dexamethasone 4mg iv (100-200mcg/kg up to 8mg in children) if not already given within past 8hrs
  • consider droperidol 0.625mg (adults) slow iv
• if still vomiting:
  • promethazine 12.5mg (adults) iv
• reference: Aust. Ther. Guidelines 2008

• first line tends to be a 5HT3 antagonist such as ondansetron
• there is no evidence to support the use of 5-HT3–receptor antagonists 24 hours beyond the last dose of radiation therapy.

• classically associated with relief from hot showers resulting in compulsive showers/bathing
• cyclical every 2-3weeks
• anti-emetics generally do not work well
• see cannabinoid hyperemesis