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1. Antiemetics
Prof. Hanan Hagar
Pharmacology Department
College of Medicine

2. Learning objectives
 Classify the main different classes of antiemetic drugsClassify the main different classes of antiemetic drugs
according to their mechanism of action.according to their mechanism of action.
 Know the characteristic pharmacokinetics & dynamics ofKnow the characteristic pharmacokinetics & dynamics of
different classes of antiemetic drugs.different classes of antiemetic drugs.
 Identify the selective drugs that can be used according toIdentify the selective drugs that can be used according to
the cause of vomiting.the cause of vomiting.
 Learn the Adjuvant antiemetics.Learn the Adjuvant antiemetics.
 Describe the major side effects for the different classes ofDescribe the major side effects for the different classes of
antiemetics.antiemetics.

3. Causes of VomitingCauses of Vomiting
Nausea and vomiting may be manifestationsNausea and vomiting may be manifestations
of many conditions and may occur due toof many conditions and may occur due to
stimulation ofstimulation of vomiting center that respond tovomiting center that respond to
inputs from:inputs from:
 Chemoreceptor trigger zoneChemoreceptor trigger zone (CTZ)(CTZ) stimulationstimulation
 Disturbance ofDisturbance of vestibular systemvestibular system
 Higher cortical centers stimulationHigher cortical centers stimulation (CNS)(CNS)
 TheThe periphery (Pharynx, GIT)periphery (Pharynx, GIT) via sensory nervesvia sensory nerves

4. 1.1. Chemoreceptor trigger zone stimulationChemoreceptor trigger zone stimulation
 CTZ is an area of medulla that communicateCTZ is an area of medulla that communicate
with vomiting center to initiate vomiting.with vomiting center to initiate vomiting.
 CTZ is physiologically outside BBB.CTZ is physiologically outside BBB.
 CTZ ContainsCTZ Contains opioid receptors, D2opioid receptors, D2
receptors & 5 HT3 receptors, Substance Preceptors & 5 HT3 receptors, Substance P
 stimulated by:stimulated by:
 Drugs (opioids, general anesthetics),Drugs (opioids, general anesthetics),
 Chemicals and toxinsChemicals and toxins in blood, CSFin blood, CSF..
 Radiation.Radiation.

5. 2. The periphery via sensory nerves2. The periphery via sensory nerves
GIT irritation, myocardial infarction, renal orGIT irritation, myocardial infarction, renal or
biliay stones.biliay stones.
3. Disturbance of vestibular system3. Disturbance of vestibular system
by motion sicknessby motion sickness
4. Higher cortical centers stimulation4. Higher cortical centers stimulation::
emotional factors, nauseating smells or sights.emotional factors, nauseating smells or sights.

6. Receptors Associated with Nausea and VomitingReceptors Associated with Nausea and Vomiting

7. Vomiting Centre
(medulla)
Cerebral cortex
Anticipatory emesis
Smell
Sight
Thought
Vestibular
nuclei
Motion
sickness
Pharynx & GIT
Chemo & radio therapy
Gastroenteritis
Chemoreceptor
Trigger Zone
(CTZ)
(Outside BBB)
chemotherapy
Opioids
Anesthetics
Muscarinic, 5 HT3 &
Histaminic H1
5 HT3 receptors
5 HT3
Dopamine D2
Opioid receptors
Substance p
Muscarinic
Histaminic H1
Pat h op h y siolog y of Em e sis

8. Chemical transmitters & receptorsChemical transmitters & receptors
involved in vomiting include:involved in vomiting include:
 AchAch (Muscarinic receptors)(Muscarinic receptors)
 DopamineDopamine (D2)(D2)
 HistamineHistamine (Histaminergic receptors H(Histaminergic receptors H11))
 SerotoninSerotonin (5 -HT(5 -HT33))
 Substance PSubstance P (Neurokinin receptors, NK1)(Neurokinin receptors, NK1)
 OpioidOpioid (Opioid receptors)(Opioid receptors)

9. Classification of Antiemetic DrugsClassification of Antiemetic Drugs
1.1. 5-HT3 antagonists5-HT3 antagonists
2.2. DD22 receptor antagonistsreceptor antagonists
3.3. NKNK11 antagonistsantagonists
4.4. HH11-receptor antagonists-receptor antagonists
5.5. Muscarinic receptor antagonistsMuscarinic receptor antagonists
6.6. CannabinoidsCannabinoids
7.7. GlucocorticoidsGlucocorticoids

11. 5-HT3 antagonists5-HT3 antagonists
 Drugs asDrugs as Ondansetron, GranisetronOndansetron, Granisetron
 Orally or parenterallyOrally or parenterally
 Potent antiemetic effectsPotent antiemetic effects
 BlockBlock 5-HT3 receptor in vomiting center, CTZ5-HT3 receptor in vomiting center, CTZ
and 5HT3 receptors on intestinal vagaland 5HT3 receptors on intestinal vagal
afferents.afferents.

12. Uses of 5-HT3 antagonistsUses of 5-HT3 antagonists
 First choice for prevention of:First choice for prevention of:
– Chemotherapy-induced nausea and vomitingChemotherapy-induced nausea and vomiting
(CINV)(CINV) especially cisplatin.especially cisplatin.
– Post-radiation NV& Post-operative NVPost-radiation NV& Post-operative NV
– Their effects is increased by combinationTheir effects is increased by combination
with corticosteroids and NK1 antagonists.with corticosteroids and NK1 antagonists.
Side effectsSide effects
oWell toleratedWell tolerated
omild headache, dizziness and constipationmild headache, dizziness and constipation
ominor ECG abnormalities (QTminor ECG abnormalities (QT
prolongation)prolongation)

13. D2 receptor antagonistsD2 receptor antagonists
 block D2 dopamine receptors in the CTZblock D2 dopamine receptors in the CTZ
 Two types exist:Two types exist:
1)1) Prokinetics drugsProkinetics drugs
2)2) Neuroleptics (antipsychotics)Neuroleptics (antipsychotics)
Uses of D2 receptor antagonistsUses of D2 receptor antagonists
 are among the most commonly used drug forare among the most commonly used drug for
nausea and vomiting of non-specific causes.nausea and vomiting of non-specific causes.
 Effective against vomiting due to drugs,Effective against vomiting due to drugs,
 gastroenteritis, post-operative, toxins,gastroenteritis, post-operative, toxins,
uremia, radiation.uremia, radiation.

14. D2 receptor antagonistsD2 receptor antagonists
1) Prokinetics drugs1) Prokinetics drugs
 Drugs as metoclopramide, domperidoneDrugs as metoclopramide, domperidone
 Both are prokinetic agents due to theirBoth are prokinetic agents due to their 5 HT45 HT4
agonistic activity.agonistic activity.
 used in GERD (gastroesophageal refluxused in GERD (gastroesophageal reflux
disease), gastroparesis.disease), gastroparesis.
 Used as antiemeticsUsed as antiemetics (blocking D2 receptors)(blocking D2 receptors)
 Metoclopramide crosses BBB butMetoclopramide crosses BBB but
domperidone cannotdomperidone cannot (both have antiemetic(both have antiemetic
effects as CTZ is outside BBB).effects as CTZ is outside BBB).

15. Side effectsSide effects (only for metoclopramide):(only for metoclopramide):
 Dyskinesia (Dyskinesia (extra-pyramidal side effects)extra-pyramidal side effects),,
 Galactorrhea, menstrual disorders,Galactorrhea, menstrual disorders,
impotence.impotence.
 Sedation, postural hypotension.Sedation, postural hypotension.

16. D2 receptor antagonistsD2 receptor antagonists
Neuroleptics (Antipsychotics)Neuroleptics (Antipsychotics)
 Chlorpromazine (CPZ), droperidolChlorpromazine (CPZ), droperidol
 used forused for postoperative vomiting andpostoperative vomiting and
chemotherapy-induced nausea & vomiting.chemotherapy-induced nausea & vomiting.
 Side effectsSide effects: extrapyramidal symptoms: extrapyramidal symptoms
sedation, postural hypotensionsedation, postural hypotension

17. Neurokinin1 (NK1) receptor antagonistsNeurokinin1 (NK1) receptor antagonists
AprepitantAprepitant
 Is a substance P antagonists that acts byIs a substance P antagonists that acts by
blocking neurokinin 1 receptors.blocking neurokinin 1 receptors.
 OrallyOrally
 Used in prevention of acute and delayedUsed in prevention of acute and delayed
chemotherapy-induced nausea and vomitingchemotherapy-induced nausea and vomiting
and for prevention of postoperative nauseaand for prevention of postoperative nausea
and vomiting.and vomiting.
 Usually combined with 5-HTUsually combined with 5-HT33 antagonistsantagonists
and corticosteroids.and corticosteroids.

18. H1-receptor antagonistsH1-receptor antagonists
 Effective for motion sickness, morningEffective for motion sickness, morning
sickness in pregnancysickness in pregnancy
 Drugs asDrugs as
– DiphenhydramineDiphenhydramine
– Meclizine - CyclizineMeclizine - Cyclizine
– Promethazine: severe morning sickness ofPromethazine: severe morning sickness of
pregnancypregnancy (if only essential).(if only essential).
Side effects:Side effects:
– prominent sedation, hypotension,prominent sedation, hypotension,
anticholinergic effects (dry mouth, dilatedanticholinergic effects (dry mouth, dilated
pupils, urinary retention, constipation.pupils, urinary retention, constipation.

19. Muscarinic receptor antagonistsMuscarinic receptor antagonists
 Hyoscine (scopolamine)Hyoscine (scopolamine)
 Orally, injection, patchesOrally, injection, patches
 Used as transdermal patches in motionUsed as transdermal patches in motion
sicknesssickness (applied behind the external ear)(applied behind the external ear)..
 Not in chemotherapy-induced vomitingNot in chemotherapy-induced vomiting
 Side effects:Side effects: tachycardia, blurred vision,tachycardia, blurred vision,
dry mouth, constipation, urinary retentiondry mouth, constipation, urinary retention
(atropine-like actions).(atropine-like actions).

20. CannabinoidsCannabinoids
 Nabilone, dronabinolNabilone, dronabinol
 mechanism of action not understood.mechanism of action not understood.
 act at central cannabinoid receptors.act at central cannabinoid receptors.
 Used in vomiting due to cytotoxicUsed in vomiting due to cytotoxic
anticancer drugsanticancer drugs (adjuvant therapy).(adjuvant therapy).
 Not commonly used.Not commonly used.
Side effects:Side effects: euphoria, dysphoria, sedation,euphoria, dysphoria, sedation,
hallucination.hallucination.

21. GlucocorticoidsGlucocorticoids
 Dexamethasone -Dexamethasone - methylprednisolonemethylprednisolone
 Used in chemotherapy-induced vomitingUsed in chemotherapy-induced vomiting
 combined withcombined with 5-HT5-HT33 antagonists or NK1antagonists or NK1
receptor antagonists.receptor antagonists.

22. GlucocorticoidsGlucocorticoids
 Side effects:Side effects:
– HyperglycemiaHyperglycemia
– Hypertension
– Cataract
– Osteoporosis
– Increased intraocular pressure
– Increased susceptibility to infection
– Increased appetite & obesity

23. SummarySummary
The choice of antiemetic depends on the etiologyThe choice of antiemetic depends on the etiology
Motion sicknessMotion sickness
Muscarinic antagonistsMuscarinic antagonists
AntihistaminicsAntihistaminics
Vomiting with pregnancy (morning sicknessVomiting with pregnancy (morning sickness((
avoid all drugs in the first trimesteravoid all drugs in the first trimester
Pyridoxine (B6Pyridoxine (B6((
Promethazine ( late pregnancyPromethazine ( late pregnancy(.(.

24. Drug- induced vomiting (CTZDrug- induced vomiting (CTZ((
Dopamine antagonistsDopamine antagonists
Post operative nausea & vomitingPost operative nausea & vomiting
Dopamine antagonistsDopamine antagonists
55--HTHT33 antagonistsantagonists
NK1 antagonistsNK1 antagonists
Vomiting due to cytotoxic drugsVomiting due to cytotoxic drugs..
55--HTHT33 antagonistsantagonists
NK1 antagonistsNK1 antagonists
D2- antagonistsD2- antagonists
GlucocorticoidsGlucocorticoids

25. Thank you
Questions?