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Bilateral vomiting
centres
The chemoreceptor
trigger zone
Inputs from the vestibular system
of the inner ear.
• Motion sickness.
• Via vestibulocochlear
nerve
• Involvement of H1 type
of histamine receptors in
this system
The enteric nervous system also transmits
signals to the brain via the vagus nerve.
• Activation of 5-HT3 receptors
leading to vomiting
• Drug induced vomiting
• Gag reflex: pharyngeal stimulation
of vagus nerve
Visceral afferents from the gastrointestinal tract (vagus or sympathetic
nerves) - these signals inform the brain of such conditions as
gastrointestinal distention (a very potent stimulus for vomition) and
mucosal irritation.
Visceral afferents from outside the gastrointestinal tract - this includes
signals from bile ducts, peritoneum, heart and a variety of other organs.
Afferents from extramedullary centers in the brain - it is clear that certain
psychic stimuli (odors, fear), vestibular disturbances (motion sickness) and
cerebral trauma can result in vomition.
The chemoreceptor trigger zone
Receptors and neurotransmitters involved in mediating vomiting:
Structures Receptors Agonists Antagonists
Area
postrema
CTZ
D2 Apomorphine
L-DOPA
Antidopaminergi
c drugs
Vestibular
nuclei
N. tractus
solitarius
M, H1 Cholinomimetics
Histamine
Scopolamine
Dramamine
Vomiting
center
M Cholinomimetics
(e.g.,
physostigmine)
Scopolamine
Vagal
sensory
nerve
endings
5-HT3 Serotonin Ondansetron
Granisetron
Tropisetron
Vomiting Centre
(medulla)
Cerebral cortex
Anticipatory emesis
Smell
Sight
Thought
Vestibular
nucleiMotion
sickness
Pharynx & GIT
Chemo & radio therapy
Gastroenteritis
Chemoreceptor
Trigger Zone
(CTZ)
(Outside BBB)
Cancer chemotherapy
Opioids
Muscarinic, 5 HT3 &
Histaminic H1
5 HT3 receptors
Dopamine D2
5 HT3,,
Opioid Receptors
Muscarinic
Histaminic H1
Pathophysiology of Emesis
NAUSEA
RETCHING
VOMETING
An unpleasant sensation that immediately
precedes vomiting
Labored spasmodic respiratory movements
against a closed glottis with contractions of the
abdominal muscles, chest wall and diaphragm
Intense contraction of the abdominal muscles and
relaxation of the upper esophageal sphincter
Rapid and forceful evacuation of stomach
contents up to and out of the mouth
Groups Drugs
Selective 5-HT3 Antagonists Ondansetron, Granisetron, Palonosetron &
Dolasetron.
D2 Antagonists
• Substituted Benzamides Metoclopramide
• Butyrophenones Domperidone
• Neuroleptics Chlorpromazine, Triflupromazine,
Prochlorperazine,
H1 Antihistaminics Promethazine, Diphenhydramine,
Dimenhydrinate, Doxylamine
Anticholinergics Hyoscine, Dicyclomine
Cannabinoids Dronabinol , Nabilone
Glucocorticoids Dexamethasone, Methylprednisolone
Benzodiazepines Diazepam , Lorazepam
Neurokinin-I Antagonist Aprepitant (oral formulation),
Fosaprepitant (IV formulation)
D2 antagonism: Central antidopaminergic
(D2) action of metoclopramide on CTZ
5-HT4 agonism: It acts in the GIT to enhance
Ach release from the myenteric motor
neurons
5HT3 antagonism: At higher concentrations
it blocks 5HT3 receptors in the inhibitory
myentric interneurons and in the CTZ
Neuroleptics
Phenothiazines:
Prochlorperazine
Promethazine
Triflupromazine
Phenothiazines are antipsychotics with potent antiemetic property due
to D2 antagonism and anti-muscarinic properties H1 and
antihistaminic property.
Most of these drugs produce significant degree of sedation. Acute
muscle dystonia may occur
Domperidone (X)
The combination of pyridoxine 10 mg and doxylamine 10 mg was withdrawn
from the market due to increased risk of birth defects with the combination.
Doxylamine/pyridoxine:
• The only FDA-approved drug for treating nausea and vomiting in pregnancy
• A greater form of reduction in Hyperemesis gravidarum
• No teratogenic potential
Ondansetron :
• Class B safety in pregnancy
• Most common parenteral and oral antiemetic used due to its efficacy
Anticholinergics may be used as supportive drugs.
Ginger capsules: 250 mg taken 4 times a day have been demonstrated to be effective
against nausea and vomiting of pregnancy
High Moderate Low Minimal
Intravenous Cisplatin Alemtuzumab Bortezomib Bevacizumab
Cyclophospha-
mide
Cyclophospha
mid
Cetuximab Bleomycin
Gemcitabine Rituximab
Dacarbazine Doxorubicin Docetaxel Vinblastine
Carmustine Epirubicin Etoposide Vincristine
Oral Procarbazine Imatinib Capecitabine Hydroxyurea
Hexamethyl-
melamine
Cyclophospha
mide
Etoposide Methotrexate
Emesis and anti emetic drugs
Emesis and anti emetic drugs
Emesis and anti emetic drugs

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Emesis and anti emetic drugs

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  • 6. Inputs from the vestibular system of the inner ear. • Motion sickness. • Via vestibulocochlear nerve • Involvement of H1 type of histamine receptors in this system The enteric nervous system also transmits signals to the brain via the vagus nerve. • Activation of 5-HT3 receptors leading to vomiting • Drug induced vomiting • Gag reflex: pharyngeal stimulation of vagus nerve
  • 7. Visceral afferents from the gastrointestinal tract (vagus or sympathetic nerves) - these signals inform the brain of such conditions as gastrointestinal distention (a very potent stimulus for vomition) and mucosal irritation. Visceral afferents from outside the gastrointestinal tract - this includes signals from bile ducts, peritoneum, heart and a variety of other organs. Afferents from extramedullary centers in the brain - it is clear that certain psychic stimuli (odors, fear), vestibular disturbances (motion sickness) and cerebral trauma can result in vomition. The chemoreceptor trigger zone
  • 8. Receptors and neurotransmitters involved in mediating vomiting: Structures Receptors Agonists Antagonists Area postrema CTZ D2 Apomorphine L-DOPA Antidopaminergi c drugs Vestibular nuclei N. tractus solitarius M, H1 Cholinomimetics Histamine Scopolamine Dramamine Vomiting center M Cholinomimetics (e.g., physostigmine) Scopolamine Vagal sensory nerve endings 5-HT3 Serotonin Ondansetron Granisetron Tropisetron
  • 9. Vomiting Centre (medulla) Cerebral cortex Anticipatory emesis Smell Sight Thought Vestibular nucleiMotion sickness Pharynx & GIT Chemo & radio therapy Gastroenteritis Chemoreceptor Trigger Zone (CTZ) (Outside BBB) Cancer chemotherapy Opioids Muscarinic, 5 HT3 & Histaminic H1 5 HT3 receptors Dopamine D2 5 HT3,, Opioid Receptors Muscarinic Histaminic H1 Pathophysiology of Emesis
  • 10. NAUSEA RETCHING VOMETING An unpleasant sensation that immediately precedes vomiting Labored spasmodic respiratory movements against a closed glottis with contractions of the abdominal muscles, chest wall and diaphragm Intense contraction of the abdominal muscles and relaxation of the upper esophageal sphincter Rapid and forceful evacuation of stomach contents up to and out of the mouth
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  • 17.
  • 18.
  • 19. Groups Drugs Selective 5-HT3 Antagonists Ondansetron, Granisetron, Palonosetron & Dolasetron. D2 Antagonists • Substituted Benzamides Metoclopramide • Butyrophenones Domperidone • Neuroleptics Chlorpromazine, Triflupromazine, Prochlorperazine, H1 Antihistaminics Promethazine, Diphenhydramine, Dimenhydrinate, Doxylamine Anticholinergics Hyoscine, Dicyclomine
  • 20. Cannabinoids Dronabinol , Nabilone Glucocorticoids Dexamethasone, Methylprednisolone Benzodiazepines Diazepam , Lorazepam Neurokinin-I Antagonist Aprepitant (oral formulation), Fosaprepitant (IV formulation)
  • 21.
  • 22.
  • 23.
  • 24.
  • 25.
  • 26.
  • 27.
  • 28. D2 antagonism: Central antidopaminergic (D2) action of metoclopramide on CTZ 5-HT4 agonism: It acts in the GIT to enhance Ach release from the myenteric motor neurons 5HT3 antagonism: At higher concentrations it blocks 5HT3 receptors in the inhibitory myentric interneurons and in the CTZ
  • 29.
  • 30.
  • 31.
  • 32.
  • 33.
  • 34.
  • 35. Neuroleptics Phenothiazines: Prochlorperazine Promethazine Triflupromazine Phenothiazines are antipsychotics with potent antiemetic property due to D2 antagonism and anti-muscarinic properties H1 and antihistaminic property. Most of these drugs produce significant degree of sedation. Acute muscle dystonia may occur
  • 36.
  • 37.
  • 38.
  • 39.
  • 40.
  • 41.
  • 42.
  • 43. Domperidone (X) The combination of pyridoxine 10 mg and doxylamine 10 mg was withdrawn from the market due to increased risk of birth defects with the combination. Doxylamine/pyridoxine: • The only FDA-approved drug for treating nausea and vomiting in pregnancy • A greater form of reduction in Hyperemesis gravidarum • No teratogenic potential Ondansetron : • Class B safety in pregnancy • Most common parenteral and oral antiemetic used due to its efficacy Anticholinergics may be used as supportive drugs. Ginger capsules: 250 mg taken 4 times a day have been demonstrated to be effective against nausea and vomiting of pregnancy
  • 44.
  • 45. High Moderate Low Minimal Intravenous Cisplatin Alemtuzumab Bortezomib Bevacizumab Cyclophospha- mide Cyclophospha mid Cetuximab Bleomycin Gemcitabine Rituximab Dacarbazine Doxorubicin Docetaxel Vinblastine Carmustine Epirubicin Etoposide Vincristine Oral Procarbazine Imatinib Capecitabine Hydroxyurea Hexamethyl- melamine Cyclophospha mide Etoposide Methotrexate

Editor's Notes

  1. is a bilateral set of centers in the brainstem lying under the floor of the fourth ventricle
  2. In astudy, 61.8 percent of pregnant women with hyper-emesis were found to be positive for the H. pylori genome,