AntiemeticsDr.S.ManikandanDepartment of PharmacologyJawaharlal Institute of Postgraduate Medical Education and Research (JIPMER),Pondicherry. INDIA.

Manikandan *Vomiting Centre (medulla)Cerebral cortexAnticipatory emesisSmellSightThoughtVestibular nucleiMotion sicknessPharynx & GITChemo & radio therapy GastroenteritisChemoreceptor Trigger Zone (CTZ)(Outside BBB)Cancer chemotherapyOpioidsMuscarinic, 5 HT3 & Histaminic H15 HT3 receptorsDopamine D2 5 HT3,,Opioid Receptors Muscarinic Histaminic H1Pathophysiology of Emesis

Manikandan *Now answer this questionWhich group of drugs can be used as antiemetics ?Serotonin 5 HT3 AntagonistsDopamine D2 AntagonistAnticholinergicsH1 AntihistaminicsCannabinoids

Manikandan *Serotonin 5 HT3 AntagonistPotent antiemeticsEven though 5 HT3 receptors are present in vomiting centre & CTZ, the antiemetic action is restricted to emesis caused by vagal stimulation. High first pass metabolismExcreted by liver & kidneyNo dose reduction in renal insufficiency but needed in hepatic insufficiencyGiven once or twice daily orally or intravenously.

Manikandan *Drugs AvailableOndansetron 32 mg / dayGranisetron 10 mg / kg / day Dolasetron 1.8 mg / kg / dayIndicationsChemotherapy induced nausea & vomiting given 30 min. before chemotherapy.Postoperative & postradiation nausea & vomiting

Manikandan *Adverse EffectsExcellent safety profileHeadache & constipationAll three drugs cause prolongation of QT interval, but more pronounced with dolasetron.

Manikandan *Dopamine D2 AntagonistAntagonise 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.

Manikandan *Now answer this questionWhich 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.

Manikandan *Phenothiazines & ButyrophenonesPhenothiazines Prochlorperazine PromethazinePhenothiazines are antipsychotics with potent antiemetic property due to D2 antagonism.Butyrophenone DroperidolDroperidol used for postop. nausea & vomiting, but cause QT prolongation.

Manikandan *H1 AntihistaminicsMost effective drugs for motion sicknessDrugs available Meclizine Cyclizine Dimenhydrinate Diphenydramine Promethazine Used in pregnancy, used by NASA for space motion sickness

Manikandan *AnticholinergicsScopolamine (hyoscine) used as transdermal patch for motion sicknessCannabinoidsDronabinol used as adjuvant in chemotherapy induced vomiting.It is a psychoactive substance Nabilone

Manikandan *Now answer this questionA 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 ?

Manikandan *Explanation : Vestibular nuclei has only muscarinic and H1 histaminic receptors.

Manikandan *Points to Ponder

Manikandan *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?

Manikandan *