1. Department of Pharmacology
Antiemetics
Dr.S.Manikandan
Department of Pharmacology
Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER),
Pondicherry. INDIA.

2. Pathophysiology of Emesis
Cerebral cortex
Cancer chemotherapy
Opioids
Smell
Sight
Thought
Anticipatory emesis
Chemoreceptor Trigger Zone (CTZ)
Vestibular nuclei
Vomiting Centre (medulla)
Motion sickness
Muscarinic Histaminic H1
Muscarinic, 5 HT3 & Histaminic H1
(Outside BBB)
Dopamine D2
5 HT3,,Opioid Receptors
Chemo & radio therapy Gastroenteritis
Pharynx & GIT
5 HT3 receptors
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3. Now answer this question
Which group of drugs can be used as antiemetics ?
Serotonin 5 HT3 Antagonists
Dopamine D2 Antagonist
Anticholinergics
H1 Antihistaminics
Cannabinoids
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4. Serotonin 5 HT3 Antagonist
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.
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5. Drugs Available Indications Ondansetron 32 mg / day
Granisetron mg / kg / day
Dolasetron mg / kg / day
Indications
Chemotherapy induced nausea & vomiting – given 30 min. before chemotherapy.
Postoperative & postradiation nausea & vomiting
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6. Adverse Effects Excellent safety profile Headache & constipation
All three drugs cause prolongation of QT interval, but more pronounced with dolasetron.
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7. Dopamine D2 Antagonist Antagonise D2 receptors in CTZ. Drugs available
Metoclopramide mg b.d
Domperidone 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.
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8. Now answer this question
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.
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9. Phenothiazines & Butyrophenones
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.
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10. H1 Antihistaminics Most effective drugs for motion sickness
Drugs available
Meclizine
Cyclizine
Dimenhydrinate
Diphenydramine
Promethazine – Used in pregnancy, used by
NASA for space motion sickness
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11. Anticholinergics Cannabinoids
Scopolamine (hyoscine) – used as transdermal patch for motion sickness
Cannabinoids
Dronabinol – used as adjuvant in chemotherapy induced vomiting.It is a psychoactive substance
Nabilone
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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 ?
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13. Vestibular nuclei has only muscarinic and H1 histaminic receptors.
Explanation :
Vestibular nuclei has only muscarinic and H1 histaminic receptors.
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14. Points to Ponder
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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?
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16. Thank you
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