Vomiting can occur due to various causes like chemotherapy, radiation therapy, pregnancy, motion sickness, increased intracranial pressure, and more. It involves three phases - nausea, retching, and vomiting mediated by chemoreceptor trigger zone and vomiting center. Various drugs act on receptors like histamine H1, muscarinic, dopamine D2, 5-HT3 receptors to treat conditions causing nausea and vomiting. Phenothiazines, 5-HT3 antagonists, metoclopramide, cannabinoids, and corticosteroids are commonly used antiemetics for conditions like chemotherapy side effects, vertigo, and morning sickness.

1. VOMITING
(Emesis)

2. What is the major physiological
function of vomiting
to remove non-toxic or
harmless substances
from the body after
ingestion

3. EMESIS
CAN IT BE BENEFICIAL

4. VALUABLE PHYSIOLOGICAL
RESPONSE TO INGESTION OF
TOXIC SUBSTANCES E.G.
ALCOHOL

5. Can you tell us
some clinical
problems that might
occur due to nausea
and vomiting

6. postoperative nausea and
vomiting
• Extended hospital stays,
• Increased bleeding,
• Aspiration pneumonia
• Re-opening of surgical
wounds

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.

12. Neuronal pathways,
transmitters and
receptors involved in
nausea and vomiting

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

15. Afferent neuronal pathways
from the abdomen are the
same regardless of the
stimulus.

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.

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

23. Class Drug
Anti-cholinergic scopolamine (L-hyoscine)
Anti-histamine cinnarizine
cyclizine
promethazine
Dopamine antagonists metoclopramide
domperidone
droperidol (withdrawn 2001)
haloperidol
Cannabinoid nabilone
Corticosteroid dexamethasone
Histamine analogue betahistine
5HT3
-receptor antagonist granisetron
ondansetron
tropisetron

24. Causes of Vomiting

25. Drug/treatment - induced Cancer chemotherapy
Opiates, Nicotine
Antibiotics, Radiotherapy
Labyrinth disorders Motion, Meniere's disease
Endocrine causes Pregnancy
nfectious causes Gastroenteritis
Viral labyrinthitis
ncreased intracranial
pressure
Haemorrhage, Meningitis
Post-operative Anaesthetics, Analgesics
Procedural
CNS causes Anticipatory
Migraine, Bulimia nervosa

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

29. The management of
Nausea &Vomiting

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

31. Antiemetics

32. Class Drug
Anti-cholinergic scopolamine (L-hyoscine)
Anti-histamine cinnarizine
cyclizine
promethazine
Dopamine antagonists metoclopramide
domperidone
droperidol (withdrawn 2001)
haloperidol
Cannabinoid nabilone
Corticosteroid dexamethasone
Histamine analogue betahistine
5HT3
-receptor antagonist granisetron
ondansetron
tropisetron

33. Receptors antagonists
•Which receptors
 H1 - Histamine receptors
 Muscarinic receptors
 5 HT 3 receptors

35. Antiemetic Drugs
H1- receptor antagonist
• Cyclizine
• Meclizine
• Cinnarazine
• Promethazin
• Diphenhydramine
• Dimenhydrinate
• Hydroxyzine
Muscarinic antagonist
• Hyoscine (Scopolamine)

36. D2-receptor antagonist
Phenothiazine
• Chlorpromazine,
prochlorperazine,Promethazine
Trifluoperazine. Thiethylperazine.
Butyrophenones:
• Haloperidol
• Droperidol
Metoclopramide
Domperidone

37. 5 HT3-receptor antagonist
Ondansetron
Granisetron
Dolasetron
Cannabinoids
• Nabilone
• Dronabinol
Steroids
• Dexamethasone
• Methylprednisolone

38. Clinical Uses of Anti emetics
• Histamine H1 receptor antagonist
Cyclizine Motion sickness
Cinnarazine Motion sickness,
vestibular disorders
Promethazine Morning sickness of
pregnancy

39. Muscarinic antagonist
Hyoscine Motion sickness

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
Increase the motility of
esophagus, stomach, and intestine

45. Cannabinoids
Dronabinol, Nabilone
• Synthetic cannabinol derivative
• Mechanism of action: unknown
Adverse effects: common:
• Drowsiness,dizziness, dry mouth.
• Mood changes
• Postural hypotension
• Hallucinations

46. Corticosteroids
High dose Glucocorticoids
• Dexamethasone
• Methylprednisolone
• Mechanism of action: unclear
may involve inhibition
of PGs