This document discusses the neuroanatomy and pharmacology of nausea and vomiting. It outlines the various receptor types involved in emesis, including dopamine, 5-HT3, opioid, histamine, and muscarinic receptors. It then describes different drug classes that act on these receptors, such as 5-HT3 antagonists, phenothiazines, butyrophenones, antihistamines, corticosteroids, cannabinoids, metoclopramide, domperidone, cisapride and other prokinetic agents. The mechanisms of action, uses, and adverse effects of selected antiemetic medications are also summarized.

1. Dr. RAGHU PRASADA M S
MBBS,MD
ASSISTANT PROFESSOR
DEPT. OF PHARMACOLOGY
SSIMS & RC.
1

2. Vomiting Centre
(medulla)
Stomach
Small intestine
Higher cortical
centres
Chemoreceptor
Trigger Zone
(area prostrema,
4th ventricle)
Memory, fear, anticipationSensory input (pain, smell, sight)
Surgery
Surgery
Labyrinths
Anaesthetics
Vomiting Reflex
Neuronal pathways
Factors which can
cause nausea & vomiting
Chemotherapy
Chemotherapy
Radiotherapy
Opioids
Sites of action of drugs
5HT3
antagonists
Sphincter modulators
Histamine antagonists
Muscarinic antagonists
Gastroprokinetic
agents
Benzodiazepines
Histamine antagonists
Muscarinic antagonists
Dopamine antagonists
Cannabinoids

3. Area Type of receptors Stimulus
Chemoreceptor trigger
zone (CTZ)
a) Dopamine D2
b) 5HT3
c) Opioid
d) H1 anti
1) Cancer chemotherapy
2) Opioids
3) Morning sickness
Vestibular nuclei a) Muscarinic
b) Histamine H1
1) Motion sickness
Pharynx and GIT a) 5HT3 1) Cancer chemotherapy
2) Radio therapy
3) Gastroenteritis
Cerebral cortex 1) Smell
2) Sight
3) Thought
4) Anticipatory emesis

4. 1. Anti-dopaminergic agents
a) Phenothiazines: Prochlorperazine, Promethazine
b) Butyrophenones : Droperidol
2. Anti- 5 HT3 antagonists: Ondansetron,Granisetron
3. Anticholinergics: Atropine, hyoscine , Glycopyrrolate
4. Anti-histamines: Cyclizine, diphenhydramine,
Cinnarizine
5. Glucocorticoids: Dexamethazone
6. Cannabinoids: Dronabinol, Nabilone
7. Miscellaneous: Diphenidol, Droperidol,
Trimethobenzamide

5. Substituted benzamides : Metoclopramide
Benzimidazole Derivative: Domperidone
Anti -5HT4 agonists: cisapride, mosopride,
zacopride, renzapride, prucalopride
Macrolides: motilin agonists: Erythromycin,
Azithromycin, Clarithromycin
CCK1 antagonist: loxiglumide

6.  Phenothiazines are primarily antipsychotic
Mechanism of the antiemetic action: inhibition
of central dopamine, muscarinic and H1
histamine receptors receptors
Use:
 Chemotherapy-induced vomiting
 Radiotherapy-induced vomiting
 postoperative nausea and vomiting

7.  are primarily antipsychotic agents
 Mechanism of the antiemetic action: inhibition
of central dopamine receptors
 Use:
 Chemotherapy-induced vomiting
 Radiotherapy-induced vomiting
 postoperative nausea and vomiting
 Adverse effects: droperidol may prolong the QT
inter, therefore, it should not be used in patients
with QT prolongation (should only be used in
patients who have not responded adequately to
alternative agents).

8. 1. Ondansetron, Granisetron, Dolasetron,
Palonosetron
2. Mechanism of action: Peripheral 5-HT3 receptor
blockade on intestinal vagal afferents.
 Central 5-HT3 receptor blockade in the vomiting
center and chemoreceptor trigger zone
 High first pass metabolism
 Excreted by liver & kidney

9. 1) Chemotherapy induced nausea and vomiting
2) Post radiation nausea & vomiting
3) Vomiting of pregnancy
4) Postoperative vomiting
Adverse drug reactions
 Headache and dizziness
 Constipation or diarrhoea

10. Dexamethazone
Corticosteroids have antiemetic properties
Mechanism of action: possibly by suppressing
peritumoral inflammation and prostaglandin
production.
Use: to enhance efficacy of 5HT3 receptor antagonists
in the treatment of chemotherapy-induced vomiting.

11. Use: prevention or treatment of motion sickness.
Adverse effects: sedation, dizziness,confusion, dry mouth,
cycloplegia, and urinary retention.
.
Diphenhydramine dimenhydrinate First generation H1 receptor blockers
that have anticholinergic and
sedating properties
Meclizine First generation H1 receptor blockers
that have lesser anticholinergic and
sedating properties
Hyoscine Muscarinic receptor blocker

12.  Pharmacokinetics: Readily absorbed after oral
administration
It undergoes extensive first-pass metabolism with
limited systemic bioavailability after single doses.
Metabolites are excreted primarily via the biliary-fecal
route
 Adverse effects: Euphoria or dysphoria, sedation
1. withdrawal syndrome (restless, insomnia and irritability)
2. Autonomic effects (sympathetic) in the form of
tachycardia, palpitation, orthostatic hypotension.
 Use: For the prevention of chemotherapy-induced
nausea and vomiting

13.  Substituted benzamides Metoclopramide
 5HT3 and 5HT4 receptor antagonist
 Mechanism of antiemetic action: Central dopamine-
receptor blockade
 Prokinetic effects- activation of 5HT4 receptors
 Side effects: (mainly extrapyramidal):
 Restlessness,Dystonias
 Parkinsonian symptoms
 Galactorrhoea and gynacomastia

14.  Structurally similar to haloperidol
 MOA similar to metaclopramide
 Used to prevent emetic side effect of
levodopa or bromocriptine

15.  Ipecac is an OTC drug
 Administration
 Take with a glass of water or fluid, not with milk or
carbonated beverage
 Vomiting occurs in 20 to 30 minutes and if not,
repeat dose
 Gastric lavage may be needed if vomiting does not
occur
 Caution: avoid vomiting if substance is caustic or
petroleum
 Apomorphine is a morphine derive emetic, SQ/IM,
Onset 15 min

16.  Cisapride, Mosopride, Zacopride, Renzapride,
Prucalopride
 -no antiemetic effect
 Promote release of Ach from myentric plexus
 Cisapride- facilitates gastric motility,
throughout the GIT
 Hastens gastric emptying, improves LES tone
 And oesophageal peristalsis.

17.  Abdominal cramps, diarrhoea
 QT prolongation
 Cytochrome P450 inhibition


18.  Motilin receptors
 Increase LES tone
 CCK1 receptor antagonist
 Loxiglumide –increase GI motility