AntiemeticsAntiemetics

Dr.S.Manikandan

Department of Pharmacology

Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER),

Pondicherry. INDIA.

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Vomiting Centre (medulla)

Cerebral cortex

Anticipatory emesisSmellSight

Thought

Vestibular nucleiMotion

sickness

Pharynx & GIT

Chemo & radio therapy Gastroenteritis

Chemoreceptor Trigger Zone

(CTZ)(Outside BBB)

Cancer chemotherapyOpioids

Muscarinic, 5 HT3 & Histaminic H1

5 HT3 receptors

Dopamine D2

5 HT3,,Opioid Receptors

Muscarinic Histaminic H1

P athophysiology of Emesis

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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 HT 3 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 AvailableOndansetron 32 mg / day

Granisetron 10 µg / kg / day

Dolasetron 1.8 mg / kg / day

I ndicationsChemotherapy induced nausea & vomiting – given

30 min. before chemotherapy.

Postoperative & postradiation nausea & vomiting

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Adverse EffectsExcellent safety profile

Headache & constipation

All three drugs cause prolongation of QT interval, but more pronounced with dolasetron.

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Dopamine D 2 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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P henothiazines & 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 didn’t 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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