Antiemetics Pharmacology

2. 1. Pathophysiology of Vomiting
2. Classification of drugs used in Vomiting
3. Explain Mechanism of action of antiemetic
drugs

3. Manikandan 3
Vomiting Centre
(medulla)
Cerebral cortex
Anticipatory emesis
Smell
Sight
Thought
Vestibular
nucleiMotion
sickness
Pharynx & GIT
Chemo & radio therapy
Gastroenteritis
Chemoreceptor
Trigger Zone
(CTZ)
(Outside BBB)
Cancer chemotherapy
Opioids
Muscarinic, 5 HT3 &
Histaminic H1
5 HT3 receptors
Dopamine D2
5 HT3,,Opioid
Receptors
Muscarinic
Histaminic H1
Pathophysiology of vomiting

4. Manikandan 4
Now answer this question
Which group of drugs can be used as antiemetics ?
 Muscarinic antagonis
 H1 Antagonist
 Serotonin 5 HT3 Antagonists
 Dopamine D2 Antagonist
 Cannabinoids

5. Manikandan 5
Classification of drugs used in
Vomiting

6. Manikandan 6
1. Anticholinergics
 Scopolamine (hyoscine) –
used as transdermal patch for motion sickness

7.  Useful in motion sickness
 Morning sickness
 Postoperative and other form of vomiting
 Their antiemetic action based on anticholinergic,
antihistaminic, and sedative property.
 Drugs- promethazine, Diphenhydramine,
cyclizine, meclizine, cinnarazine
Manikandan 7
2. H1 antagonist

8. Manikandan 8
3. 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.

9. Manikandan 9
Drugs Available
 Ondansetron 32 mg / day
 Granisetron 10 mg / kg / day
 Dolasetron 1.8 mg / kg / day
Indications
 Chemotherapy induced nausea & vomiting – given
30 min. before chemotherapy.
 Postoperative & postradiation nausea & vomiting

10. Manikandan 10
Adverse Effects
 Excellent safety profile
 Headache & constipation
 All three drugs cause prolongation of QT interval,
but more pronounced with dolasetron.

11. Manikandan 11
4. D2 antagonist - Prokinetic drug
 MOA- Antagonise D2 receptors in CTZ.
 Drugs available
Metoclopramide 2.5 mg b.d
Domperidone 10 mg b.d
 Both drugs acts as antidopaminergic also
prokinetic agents due to their 5 HT4 agonist activity.
 Domperidone – oral ; Metoclopramide – oral & i.v
 Metoclopramide crosses BBB but domperidone
cannot.

12.  D2 antagonism – by blocking D2 receptor in GIT-
increasing gastric emptying, enhancing LES tone
by augmenting Ach release.
 5HT3 antagonism- seen only in high doses
 5-HT4 antagonism- metoclopramide acts in the
GIT to enhance Ach release from myenteric
motor neurons 5-HT4 receptor activation.
Manikandan 12

13. Manikandan 13
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.

14.  Antiemetic – metoclopramide effective in post-
operative, drug induced, diseased associated
vomiting.
 Gastrokinetic – to accelerate gastric emptying –
when emergency general anesthesia given, to,
relieve post vagotomy or diabetes associated
gastric stasis, to facilitate duodenal intubation
 Dyspepsia
 GERD
Manikandan 14

15.  Do not cross BBB
 DO NOT CAUSE EXTRAPYRAMIDAL SIDE
EFFECTS
 DOC FOR LEVODOPA INDUCED
VOMITING
 NO OTHER ACTION
Manikandan 15

16. Manikandan 18
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 ?

17. Manikandan 19
Explanation :
Vestibular nuclei has only
muscarinic and H1 histaminic receptors.

18. Manikandan 20
Points to Ponder

19. Manikandan 22
Extra-pyramidal effects
Dry mouth and blurred vision
Sedation
Tachycardia
Hypotension
Anti-emetic agents: Side effects

20. Manikandan 23
Postoperative
Chemotherapy
Travel sickness
Parkinson’s disease
(especially apomorphine)
Pregnancy
Anti-emetic agents: Choice

21. Manikandan 24