Vomiting can occur due to various causes like chemotherapy, radiation therapy, pregnancy, infections, increased intracranial pressure, and postoperative issues. It involves three phases - nausea, retching, and vomiting mediated by chemoreceptor trigger zone and vomiting center. Various drugs like antihistamines, anticholinergics, dopamine antagonists, 5HT3 antagonists, cannabinoids, and corticosteroids are used as antiemetics depending on the cause of vomiting. Their mechanism of action involves blocking receptors like histamine, muscarinic, dopamine, and 5HT3 receptors. Phenothiazines, metoclopramide, 5HT3 antagonists, and dexamethasone
7. Reflex mechanism of vomiting
• Chemoreceptor Trigger Zone (CTZ)
• Vomiting centre
Three phases:
NAUSEA, RETCHING and VOMITING
8. Nausea
• an unpleasant sensation that
immediately precedes vomiting.
Cold sweat, pallor, salivation.
Noticeable disinterest in the surroundings,
Loss of gastric tone.
Reflux of intestinal contents into the stomach
Accompanying symptoms
9. Retching
• follows nausea
comprises
labored spasmodic respiratory movements
against a closed glottis with contractions of the
abdominal muscles, chest wall and diaphragm
without any
expulsion of gastric contents.
can occur
without vomiting
but
normally it generates the pressure gradient that
leads to vomiting.
10. Vomiting
caused by:
• the powerful sustained contraction of the
abdominal and chest wall musculature,
accompanied by
• The descent of the diaphragm and the opening of
the gastric cardia.
It results in the
• rapid and forceful evacuation of stomach
contents up to and out of the mouth
Reflex activity that is not under voluntary
control.
13. Mechano and Chemo receptors
located in
• stomach, jejunum and ileum
involved with
• detection of emetic stimuli in the
gastrointestinal tract.
14. Mechanoreceptors are
tension receptors that initiate emesis
in response to
distension and contraction
e.g. from bowel obstruction.
Chemo receptors respond to
a variety of toxins in the intestinal lumina
16. 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
17. Vomiting Centre
final common pathway for efferent responses that produce emesis
• controls the act of vomiting.
• not a discrete anatomical site, but represents inter-
related neuronal networks.
• inputs include: vagal sensory pathways from the
gastro-intestinal tract and neuronal pathways from
the labyrinths, higher centres of the
cortex, intracranial pressure receptors and the
chemoreceptor trigger zone.
• When activated induces: vomiting via stimulation of
the salivary and respiratory centres and the
pharyngeal, gastrointestinal and abdominal muscles.
18. Chemoreceptor Trigger Centre
(CTZ)
• in the area prostrema of the 4th
ventricle of the brain
• acts as the entry point for emetic stimuli
• CTZ is outside the blood-brain barrier
• therefore responds to stimuli from either
the cerebral spinal fluid (CSF) or the
blood.
19.
20.
21. Mechanism
• Impulses from CTZ pass to area
of brainstem called vomiting
centre that control and integrate
the visceral and somatic
functions involved in vomiting.
22. Main neurotransmitters involved in
control of vomiting
• Acetylcholine
• Histamine
• 5-HT
• Dopamine
• Enkephalins
• Substance P
26. Drugs causing emesis.
a. Drugs acting on CTZ.
• apomorphine
• emetine (when given parenterally and only at
large doses)
• L-DOPA
• estrogens (morning sickness of pregnancy)
• ergot alkaloids
• cardiac glycosides
• opiates
• cancer chemotherapeutic agents
27. b. Drugs acting locally on the G-I tract.
• Activate enterochromaffin cells
• secrete serotonin
• acts on the 5-HT3 receptors
• at the nerve endings of the vagal sensory fibers.
• The afferent fibers transmit excitation to the N.
tractus solitarius,
• which in turn activates the VC.
• These drugs are traditionally called "local
irritants".
• Ipecac, zinc salts, copper sulfate,
28. Cancer chemotherapeutic agents and
radiation therapy
• produce free radicals
enterochromaffin cells
serotonin.
• also stimulate CTZ receptors
30. • Identification and elimination of the
underlying cause if possible
• Control of the symptoms if it is not
possible to eliminate the underlying
cause
• Correction of electrolyte, fluid or
nutritional deficiencies
40. Dopamine D2 receptor antagonist
Phenothiazines vomiting caused by
Prochlorperazine uremia, radiation,viral
gastroenteritis, severe
morning sickness of
pregnancy.
Metoclopramide uremia,
radiation, GI disorders,
cytotoxic drugs.
41. 5-HT3- receptor antagonist
Drugs Vomiting caused by
Ondansetron
Granisetron
Dolasetron
cytotoxic anticancer drugs,
post operative vomiting,
radiation induced vomiting
Cannabinoids Vomiting caused by
anticancer drugs
42. 5 HT3 Antagonists
Ondansetron, Granisetron,
Dolasetron, Tropisetron
Primary site of action: CTZ
Therapeutic Use:
chemotherapy and radiation induced
nausea & vomiting
Adverse effects: Rare (headache,GI
upsets).
43. Phenothiazines
• Antipsychotics
• Commonly used for: nausea and vomiting
associated with vertigo, motion sickness,
and migraine.
• Act mainly as: antagonist at dopamine D-2
receptors in the CTZ
• Also block: muscarinic and histamine
receptors
• Adverse effects: sedation,hypotension,
extra pyramidal symptoms
44. Metoclopramide and Domperidone
• D2 receptor antagonist in CTZ.
• Peripheral prokinetic activity:
• Domperidone does not cross BBB.
Incontrast
• Metoclopramide crosses BBB
Movement disorder, fatigue, spasmodic
torticollis, occulogyric crises, increased prolactin
release galacorrhea,menstrual irregularities
Increase the motility of
esophagus, stomach, and intestine