Antiemetics

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

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
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 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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 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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 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

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 Adverse Effects
Excellent safety profile

Headache & constipation

All three drugs cause prolongation of QT interval,

but more pronounced with dolasetron.

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 Dopamine D2 Antagonist

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.
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 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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 Phenothiazines & Butyrophenones

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.
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 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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 Anticholinergics

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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 Now answer this question

A physician prescribed Tab.Ondansetron

for prophylaxis of motion sickness. Even
though ondansetron is a potent antiemetic
it didnt produce any effect in this patient.
Can you explain why ?

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 Explanation :

Vestibular nuclei has only

muscarinic and H1 histaminic receptors.

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 Points to Ponder

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 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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