1. An mtic
tie e s
Dr.S.Manikandan
Department of Pharmacology
Jawaharlal Institute of Postgraduate Medical
Education and Research (JIPMER),
Pondicherry. INDIA.

2. P athop siolog of Emsis
hy y e
Cancer chemotherapy
Cerebral cortex
Opioids Smell
Sight Anticipatory emesis
Thought
Chemoreceptor Vestibular
Vomiting Centre
Trigger Zone Motion nuclei
(medulla) sickness
(CTZ) Muscarinic, 5 HT3 & Muscarinic
(Outside BBB) Histaminic H1 Histaminic H1
Dopamine D2
5 HT3,,Opioid Chemo & radio therapy
Receptors Gastroenteritis
Pharynx & GIT
5 HT3 receptors

3. N an e this que
ow swr stion
Which group of drugs can be used as antiemetics ?
 Serotonin 5 HT3 Antagonists
 Dopamine D2 Antagonist
 Anticholinergics
 H1 Antihistaminics
 Cannabinoids

4. Se in5HT 3 An on
roton tag ist
 Potent antiemetics
 Even though 5 HT3 receptors are present in
vomiting centre & CTZ, the antiemetic action is
restricted to emesis caused by vagal stimulation.
 High first pass metabolism
 Excreted by liver & kidney
 No dose reduction in renal insufficiency but needed
in hepatic insufficiency
 Given once or twice daily – orally or intravenously.

5. D ru s Av le
g ailab
 Ondansetron 32 mg / day
 Granisetron 10 µg / kg / day
 Dolasetron 1.8 mg / kg / day
I n ation
dic s
 Chemotherapy induced nausea & vomiting – given
30 min. before chemotherapy.
 Postoperative & postradiation nausea & vomiting

6. AdvrseEffets
e c
 Excellent safety profile
 Headache & constipation
 All three drugs cause prolongation of QT interval,
but more pronounced with dolasetron.

7. D op in D 2 An on
am e tag ist
 Antagonise D2 receptors in CTZ.
 Drugs available
Metoclopramide 2.5 mg b.d
Domperidone 10 mg b.d
 Both drugs are also prokinetic agents due to their 5
HT4 agonist activity.
 Domperidone – oral ; Metoclopramide – oral & i.v
 Metoclopramide crosses BBB but domperidone
cannot.

8. N an e this que
ow swr stion
Which is a better antiemetic – Metoclopramide or
Domperidone ?
 As CTZ is outside BBB both have antiemetic
effects.
 But as metoclopramide crosses BBB it has
adverse effects like extrapyramidal side effects..
 Domperidone is well tolerated.

9. P heothiazins & Buty heons
n e rop n e
 Phenothiazines
Prochlorperazine
Promethazine
 Phenothiazines are antipsychotics with potent
antiemetic property due to D2 antagonism.
 Butyrophenone
Droperidol
 Droperidol used for postop. nausea & vomiting,
but cause QT prolongation.

10. H1Antihistam ic
in s
 Most effective drugs for motion sickness
 Drugs available
Meclizine
Cyclizine
Dimenhydrinate
Diphenydramine
Promethazine – Used in pregnancy, used by
NASA for space motion sickness

11. An holinrg s
tic e ic
 Scopolamine (hyoscine) – used as transdermal
patch for motion sickness
C n in
anab oids
 Dronabinol – used as adjuvant in chemotherapy
induced vomiting.It is a psychoactive substance
 Nabilone

12. Now answer this question
A physician prescribed Tab.Ondansetron
for prophylaxis of motion sickness. Even
though ondansetron is a potent antiemetic
it didn’t produce any effect in this patient.
Can you explain why ?

13. Explanation :
Vestibular nuclei has only
muscarinic and H1 histaminic receptors.

14. Points to Ponder

15. Even though both atropine and
scopolamine are antimuscarinic, only
scopolamine is used in the treatment of
motion sickness. Why ?
Generally transdermal patches are
applied over the arm or chest. But
scopolamine transdermal patch is
applied behind the ear. Why?