Drugs for vomiting

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
nuclei
Motion
sickness
Pharynx & GIT
Chemo & radio therapy
Gastroenteritis
Chemoreceptor
Trigger Zone
(CTZ)
(Outside BBB)
Cancer chemotherapy
Opioids
Muscarinic, 5 HT
3&
Histaminic H
1
5 HT
3receptors
Dopamine D
2
5 HT
3,,Opioid
Receptors
Muscarinic
Histaminic H
1
Pathophysiology of vomiting

4. Manikandan 4
Now answer this question
Which group of drugs can be used as antiemetics ?
Muscarinic antagonis
H
1Antagonist
Serotonin 5 HT
3Antagonists
Dopamine D
2Antagonist
Cannabinoids

5. Manikandan5
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 sedativeproperty.
Drugs-promethazine, Diphenhydramine,
cyclizine, meclizine, cinnarazine
Manikandan 7
2. H1 antagonist

8. Manikandan 8
3. 5 HT
3Antagonist
Potent antiemetics
Even though 5 HT
3receptors 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 D
2receptors 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 HT
4agonist 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.
Manikandan12

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
Manikandan14

15. Do not cross BBB
DO NOT CAUSE EXTRAPYRAMIDAL SIDE
EFFECTS
DOC FOR LEVODOPA INDUCED
VOMITING
NO OTHER ACTION
Manikandan15

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 H
1histaminic receptors.

18. Manikandan 20
Points to Ponder

19. Manikandan22
Extra-pyramidal effects
Dry mouth and blurred vision
Sedation
Tachycardia
Hypotension
Anti-emetic agents: Side effects

20. Manikandan23
Postoperative
Chemotherapy
Travel sickness
Parkinson’s disease
(especially apomorphine)
Pregnancy
Anti-emetic agents: Choice

21. Manikandan 24