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Antiemetics

I Made Jawi

Pathophysiology of Emesis
Cancer chemotherapy
Opioids

Chemoreceptor
Trigger Zone
(CTZ)
(Outside BBB)
Dopamine D2
5 HT3,,Opioid
Receptors

Cerebral cortex
Smell
Sight
Thought

Anticipatory emesis

Vomiting Centre
(medulla)
Muscarinic, 5 HT3 &
Histaminic H1

Chemo & radio therapy


Gastroenteritis

Pharynx & GIT


5 HT3 receptors
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Motion
sickness

Vestibular
nuclei

Muscarinic
Histaminic H1

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 g / 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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