Nausea & Vomiting

• Unwanted side effects of many clinically used drugs

  • Chemotherapy
  • Opioids
  • General anaesthetics
  • Digoxin
  • SSRIs
• Symptoms of Underlying Conditions or Diseases

  • Drug toxicity
  • Pregnancy
  • Motion sickness
  • GI obstruction
  • Hepatitis / Pancreatitis
  • Myocardial infarction
  • Renal failure
  • Increased intracranial pressure
  • Asthma
  • Zollinger-Ellison Syndrome
  • Diabetes
  • Thyrotoxicosis
  • Epilepsy
• Vomiting can lead to life threatening conditions

  • Aspiration pneumonia
  • Mallory Weiss Syndrome / Tears
  • Oesophageal rupture
  • Volume and electrolyte depletion
  • Acid base imbalance
  • Malnutrition
• Nausea


  Extremely unpleasant discomfort, may occur without retching or emesis
• Stimuli for nausea


  • Labyrinth stimulation
  • Visceral pain
  • Unpleasant memories
  • Numerous drugs
  • Possibly same pathway that mediates emesis
• Nausea and Intestinal Motility

  • Gastric tone is reduced
  • Gastric peristalsis is diminished or absent
  • The tone of the duodenum and proximal jejunum tends to be increased
  • Reflux of duodenal contents in the stomach is common
• Reflex Mechanisms


  1. Defensive response to remove irritating or toxic material (Triggers release of 5-HT from the enterochromaffin cells in the intestinal mucosa, 5-HT activates vagal afferent fibres)

  2. Physical act is co-ordinated by the vomiting / emetic centre in the medulla

  3. Medulla receives input from chemoreceptor trigger zone (CTZ) in the area postrema

  4. CTZ receives inputs from the vestibular nuclei (motion sickness), Vagal afferents from the GI tract, Higher cortical centres (emotional input), Blood (circulating drugs and toxins)
• Main Neurotransmitters Involved


  • Acetylcholine (M1)
  • Histamine (H1)
  • 5-HT (5-HT3)
  • Dopamine (D2)
  • Substance P (neurokinin receptors)
• Associated Phenomena


  • Hypersalivation
  • Cardiac Rhythm Disturbances
  • Defecation
• Chemoreceptor Trigger Zone (CTZ)

  • Resides outside the blood brain barrier in the area postrema
  • Sensitive to drugs such as: apomorphine (emetogenic agent and treatment for ED; D2agonist), morphine (opioid analgesics), general anaesthetics (eg. Isofluorane), cardiac glycosides (digoxin), certain chemotherapeutic agents, maternal hormones (HCG)
  • Receptors in the CTZ - Dopamine (D2-receptors), 5-HT3
• Inflammation


  SAIDs can help with CINV by inhibiting synthesis and release of cytokines ((TNF and IL-1)
• Neurokinin (NK1)


  • Both serotonin and substance P are agonists at NK1 receptors
  • NK1 receptors found in the brainstem and CTZ
• Emetogenic Agents


  • Ipecacuanha (emetine & cephaeline) with activated charcoal (absorbs toxins)
  • Copper sulphate (CuSO4) either p.o. or i.v.
  • Apomorphine – D2 agonist for ED
• Antiemetics - H1-receptor antagonists

  • Cinnarizine
  • Cyclizine
  • Diphenhydramine
  • Promethazine
• H1-receptor antagonists


  • Effective for labyrinthes (motion sickness) and most causes nausea and vomiting
  • Have anti-muscarinic activity
  • Have mild sedative action
  • Generally effective regardless of cause of emesis
• Antiemetics - Muscarinic receptor antagonists


  • Hyoscine
  • Scopolamine
• Muscarinic receptor antagonists


  • Mainly effective for labyrinthes (motion sickness)
  • Have mild sedative action
  • Generally ineffective for agents acting on CTZ
  • Can cause blurred vision, dry mouth, urinary retention
• Antiemetics - Phenothiazines


  • Chlorpromazine
  • Trifluorphenazine
  • Prochlorphenazine
• Phenothiazines


  • Have anti-histamine & anti-muscarinic action in CTZ
  • Can be given rectally so useful if vomiting has started
  • Uses: Cytotoxic induced N&V, Post-operative N&V
• Antiemetics - Dopamine (D2-receptor) antagonists


  • Metoclopramide
  • Domperidone
• Dopamine (D2-receptor) antagonists


  • Uses: CINV & PONV
  • Can cause extrapyramidal effects and exacerbate Parkinson's Disease
  • Can stimulate prolactin release resulting in galactorrhoea
• Antiemetics - 5-HT3-antagonists


  • Ondansetron
  • Tropisetron
  • Granisetron
• 1. HT3-antagonists


  • Uses: CINV & PONV
  • Can cause headache, GI upsets (motility), depression
• Antiemetics - NK1 Antagonists

  • Prepitant
  • Fosaprepitant
  • Netupitant
  • Rolapitant
• NK1 Antagonists


  • Effective for delayed phase nausea in CINV
  • Rolapitant has a long half-life of 160 h
• Antiemetics - Tetrahydrocannabinol (THC)


  • Nabilone (synthetic derivative)
• Tetrahydrocannabinol (THC)


  • Cannabinoid receptor agonists
  • Uses: CINV and PONV
  • Acts via CB1 receptors in GIT
  • Can cause drowsiness, dizziness and dry mouth
• Antiemetics - Corticosteroids


  • High dose methylprednisolone plus phenothiazine
• Antiemetics for Anticipatory Nausea

  • Benzodiazepines
  • Propranolol
• Antiemetics for Morning Sickness

  • Metoclopramide
• Morning Sickness


  • Occurs (usually) in early pregnancy
  • Dietary and lifestyle recommendations: eat a diet rich in protein and complex carbohydrates, take plenty of fluids, eat in bed
• Hyperemesis


  • Like morning sickness, but becomes more severe and persists
  • Mother can become malnourished, with glycogen depletion, ketosis, weight loss, raised pulse, diarrhoea & sleeplessness
  • If left untreated, can lead to toxaemia with elevated temp, neuritis, dim vision, memory loss, delerium convulsions & coma