Antiemetics

DR.dr.Asep Sukohar, M.Kes

Department of Pharmacology, Faculty Of Medicine,
Lampung University

Asep Sukohar

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

Asep Sukohar

Motion
sickness

5 HT3 receptors

Vestibular
nuclei

Muscarinic
Histaminic H1

Now answer this question

Which group of drugs can be used as antiemetics ?

Serotonin 5 HT3 Antagonists

Dopamine D2 Antagonist
Anticholinergics
H1 Antihistaminics
Cannabinoids
Asep Sukohar

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.
Asep Sukohar

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

Asep Sukohar

Adverse Effects
Excellent safety profile
Headache & constipation
All three drugs cause prolongation of QT interval,

but more pronounced with dolasetron.

Asep Sukohar

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.
Asep Sukohar

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.

Asep Sukohar

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.

Asep Sukohar

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
Asep Sukohar

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
Asep Sukohar

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 ?

Asep Sukohar

 Explanation :

Vestibular nuclei has only

muscarinic and H1 histaminic receptors.

Asep Sukohar

Asep Sukohar
GG 1007

Asep Sukohar
GG 1008

Asep Sukohar