This document discusses the pathophysiology of vomiting and its control. It begins by outlining the various central and peripheral mechanisms that can trigger vomiting, including inputs from the vestibular system, enteric nervous system, and various visceral afferents. It then describes the receptors and neurotransmitters involved, including 5-HT3, dopamine D2, muscarinic, and histamine H1 receptors. Common antiemetic drugs are grouped based on their mechanisms of action, such as 5-HT3 antagonists and antihistamines. The roles of various drug classes like phenothiazines, neurokinin-1 antagonists, and cannabinoids are explained. Antiemetic treatment for nausea and vomiting

5. Bilateral vomiting
centres
The chemoreceptor
trigger zone

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

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)

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

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

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

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