Anti- emetics is a process of getting rid of stomach contents.

1. ANTI-EMETICS
SUBJECT: SYSTEMIC PHARMACOLGY
23-10-2014
MERIN BABU
M.Pharm 1st Semester
Department of Pharmacology
Amrita School Of Pharmacy, Kochi

2. NAUSEA & VOMITING
ACT OF EMESIS: To get rid the stomach and intestine toxic substances and
prevent further ingestion.
VOMITING: Expulsion of gastric contents through mouth due to mass
antiperistalsis.
NAUSEA: Uneasy feeling of vomiting.
RETCHING: Series of weaker and unproductive vomiting movements.

3. VOMITING
• Vomiting is a complex process that consists of :
• PRE-EJECTION PHASE:
Gastric relaxation and retro peristalsis.
• RETCHING:
Rhythmic action of respiratory muscles preceding vomiting and
consist of abdominal & intercoastal muscles and diaphragm against a closed
glottis.
• EJECTION:
Intense contraction of abdominal muscles and relaxation of upper
oesophageal sphincter.
• Followed by multiple autonomic phenomena:
Salivation, Shivering, Vasomotor changes

4. ANTI-EMETIC MECHANISM

5. ANTI-EMETIC MECHANISM
• Anti-emesis process is
coordinated by a central emesis
center in lateral reticular
formation of midbrain adjacent
to both chemoreceptor trigger
zone (CTZ) in the area
postrema (AP) at the bottom of
4th ventricle and solitary tract
nucleus (STN).
• Lack of blood-brain barrier
(BBB) allows CTZ to monitor
the blood and CSF for toxic
substances and to relay
information to emesis center to
trigger nausea and vomiting.

6. ANTI-EMETIC MECHANISM
 Vestibular apparatus generates impulses during motion sickness which
reach vomiting center via cerebellum. Vestibular apparatus is rich in M1, H1
receptors.
 Emesis also receives information from gut through vagus nerve (via STN)
and splanchnic afferent nerves via spinal cord. They are rich in 5HT3
receptors.
 Irritants of GIT mucosa ( irritants, chemotherapeutic drugs, radiation,
endogenous toxins and poisons ) --- release mucosal serotonin from
entero-chromaffin like cells (ECL cells) which activate 5HT3 receptors.
 Inputs to emesis center also come from cerebral cortex ( particularly in
anticipatory nausea & vomiting.
 M1, H1,5HT3 and neurokinin-1 (NK1) receptors are
present in vomiting center.

7. CLASSIFICATION OF ANTI-EMETIC DRUGS
• 5HT3 ANTAGONISTS:
Ondansetron, Granisetron, Dolansetron, Palonosetron,
Ramosetron, Tropisetron.
• CENTRALLY ACTING DOPAMINE RECEPTOR ANTAGONIST:
Metoclopramide, Domperidone, Chlorpromazine, Prochlorperazine
• HISTAMINE (H1) RECEPTOR ANTAGONIST:
Cyclizine, Promethazine, Diphenhydramine, Hydroxyzine
• ANTICHOLINERGIC ( MUSCARINIC RECEPTOR ANTAGONIST):
Hyoscine (Scopolamine)
• NEUROKININE RECEPTOR ANTAGONIST:
Aprepitant
• CANABINOID RECEPTOR AGONIST:
Dronabinol, Nabilone

8. OTHER ANTI-EMETIC DRUGS
• CORTICOSTEROIDS:
Betamethasone, Dexamethasone
• VITAMIN B6 (PYRIDOXINE):
• PHOSPHATED CARBOHYDRATE SOLUTION:

9. 5HT-3 ANTAGONISTS
DRUG MOA PK USE ADVERSE
EFFECTS
ONDANSETRON-prototype
drug
5-HT is released
from
enterochromaffin
cells (ECL) of
small intestine in
response to
chemotherapy
agents.
These stimulate
vagal afferents
initiating vomiting
reflex.
Antagonism of
5HT-3 receptors
suppress nausea
& vomiting
Anti-emetic
effect persists for
long time even
after they
disappear from
circulation.
A: well absorbed
from GIT.
M: metabolised
by CY1A2,
CYP2D6, CYP3A4
followed by
glucouridination
Chemotherap
y induced
emesis
Constipation/
Diarrhoea
Headache
Lightheadness

10. 5HT-3 ANTAGONISTS
DRUG MOA PK USE ADVERSE
EFFECTS
GRANISETRON M: liver - Chemotherapy
induced nausea
- Nausea
secondary to
upper
abdominal
irradiation
- Hyperemesis
of pregnancy
Constipation/
Diarrhoea
Headache
DOLANSETRON
PALONOSETRON M: CYP2D6
E: urine
Delayed emesis-due
to long half
life

11. DOPAMINE RECPTOR ANTAGONISTS
METOCLOPRAMIDE:
• Acts centrally blocking D2 receptors in CTZ.
• Used in nausea and vomiting due to GI disorders, in
postoperative period and vomiting due to cytotoxic
drugs and radiotherapy.
DOMPERIDONE:
• Blocks D2 receptors in CTZ and acts as antiemetic.
• Advantage: doesn’t cross BBB – rare extrapyramidal
effects
• SE: headache, dryness of mouth, diarrhoea, rashes

12. ANTI-HISTAMINERGIC DRUGS
• H1 antagonists --- useful for motion sickness and post-operative emesis.
• Act on vestibular afferents and within brainstem.
CYCLIZINE, HYDROXYCYZINE, PROMETHAZINE, DIPHENHYDRAMINE.
PROMETHAZINE:
• Most potent and effective.
• Drug must be taken 1 hr before the motion.
• Useful for chemotherapy/ radiation therapy for malignancies.

13. ANTI-CHOLINERGIC DRUGS
HYOSCINE (SCOPOLAMINE):
• Labyrinthine sedative.
 Very effective in motion sickness.
• Motion sickness is due to over stimulation of vestibular
apparatus along with psychological and environmental
factors.
 Given as transdermal patch.
 Useful for post-operative nausea & vomiting.

14. SUBSTANCE P ANTAGONISTS
Nausea and vomiting associated with Cisplatin have
2 components:
Acute Phase: within 24hrs after chemotherapy
Delayed Phase: affects only some patients ( only
days 2-5)
Antagonists for NK1 receptors for substance P
-- APREPITANT
Have anti-emetic effects in delayed nausea and
improve the efficiency of standard anti-emetic
regimen.
Aprepitant given along with highly emetogenic
chemotherapy in combination with 5HT3
ANTAGONIST + CORTICOSTEROID.

15. CANNABINOIDS
DRONABINOL- naturally occurring cannabinoid.
Stimulates CB1 subtype of cannabinoid receptors
on neuron in and around vomiting center in brain
stem.
PHARMACOKINETICS:
Highly lipid soluble drug.
Onset of action within 1 hr. Peak levels within 2-
4hrs.
E: urine.
USE:
Useful prophylactic agent in chemo patients when others are not effective.
ADVERSE EFFECTS:
Complex effects on CNS-central sympathomimetic effect.
Palpitation, tachycardia, vasodilation, hypotension.
Abrupt withdrawal --- abstinence syndrome.

16. OTHER ANTI-EMETICS
GLUCOCORTICOIDS:
DEXAMETHASONE:
• Useful for treatment in nausea in
patients with widespread cancer.
• Suppress peritumoural inflammation & PG
production.
PHOSPHATED CARBOHYDRATE SOLUTION:
• Aqueous solution of glucose, fructose and
phosphoric acid- relieve nausea.
• It is taken for a short period of time.

17. TYPES OF EMESIS
 MOTION SICKNESS
 MORNING SICKNESS (VOMITING
DURING PREGNANCY)
 CHEMOTHERAPY/ RADIATION
INDUCED NAUSEA AND EMESIS
(CIE)
 POST OPERATIVE EMESIS
 VOMITING OF VARIED ORIGIN &
ADJUVANT ANTI-EMETIC

18. TYPES OF EMESIS-MOTION SICKNESS
Result during space flights, taking off and
landing of an aeroplane etc.
It is a labyrinthine vomiting via stimulation of
vestibular nuclei.
Drugs used:
H1 ANTAGONIST/ CENTRAL ACTING
ANTICHOLINERGIC.
Hyoscine.
Side effects of hyoscine: anticholinergic
Blurred vision, dryness of mouth,
cyclopelgia, sedation and sleepiness.
DIPHENHYDRAMINE, CYCLIZINE, MECLIZINE
– prevents motion sickness and treatment of
vertigo due to labyrinth dysfunction.
CINNARAZINE-Anti vertigo drug.
Used in prevention of motion
sickness.
Acts as antihistaminic,
anticholinergic, antiserotonin &
Ca2+ channel blocker.
Inhibits influx of Ca2+ from
endolymph into vestibular
apparatus.

19. TYPES OF EMESIS-MORNING SICKNESS
• Morning sickness ( Vomiting during
pregnancy).
• During 1st trimester of pregnancy due to
effect of increased oestrogen levels on
CTZ.
• DOXYLAMINE- safest drug.
CYCLIZINE, MECLIZINE
• VITAMIN B6 (PYRIDOXINE):
High doses (60mg/d) acts as
cofactor for enzyme glutamate
decarboxylase and increases GABA.
• Inhibits neurotransmitter at CTZ.

20. TYPES OF EMESIS- CIE
• Anti-cancer drugs induce emesis by direct
activation of 5HT3 receptors in CTZ / may activate
vagal and splanchnic 5HT3 receptors to send
emetogenic signals to vomiting center through
neurotransmitters.
 ONDANSETRON
 GRANISETRON
 DOLASETRON
 TROPISETRON
 PALONOSETRON
 RAMOSETRON

21. TYPES OF EMESIS-POST OPERATIVE VOMITING
• Complications in patients receiving general
anaesthesia.
• 5HT3 ANTAGONIST- preferred
• PROCHLORAZINE- blocks Dopamine 2 and
muscarinic receptors.
• PROMETHAZINE- potent anticholinergic and
antihistaminic.

22. TYPES OF EMESIS-VOMITING OF VARIED ORIGIN
 Drug induced vomiting.
 Increased intra-cranial pressure induces emesis.
 Vomiting in patients due to brain injury, cerebral tumour,
hydrocephalous- increases CSF pressure.
- Activates receptors on CTZ.
 NABILONE, DRONABINOL.

23. REFERENCE
i. Laurence L.B, Bruce A C, Bjorn C K. Goodman and Gilman’s The
Pharmacological Basis of Therapeutics.2011. 12th edition. China: Mc
Graw Hill books; pp: 1341-6.
ii. Padmaja Udayakumar. Textbook of medical pharmacology.2nd edition.
New Delhi: CBS Publishers and distributors; pp: 326-9.
iii. Sharma HL , Sharma KK. Principles of pharmacology.2nd edition.
Hyderabad: Paras publisher; pp: 395-9.