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Emetics and antiemetics(VK)
Emesis
Is a protective mechanism which serves to eliminate

harmful substances from the stomach and duodenum

Occurs due to stimulation of the emetic center situated in

the medulla oblongata

Multiple pathways can elicit vomiting
CTZ and NTS are the most important relay areas for

afferent impulses arising from GIT, throat and other
viscera

CTZ is also accessible to blood borne drugs, mediators,

hormones, toxins etc.,
Pathophysiology of Emesis

Emesis
Cancer chemotherapy
Opioids

Chemoreceptor
Trigger Zone
(CTZ)
(Outside BBB)
D2, 5 HT3,,Opioid,H1, M1

Smell
Sight
Thought

Cerebral cortex
Anticipatory emesis

Vomiting Centre
(medulla)
M1/M3, 5 HT3 & H1

Motion
sickness
-

Vestibular
nuclei
M1, H1
-

H1 Antagonist
-

DA Antagonist
5-HT3 antagonist

Pharynx & GIT
5 HT3 receptors

Chemo & radio therapy
Gastroenteritis

Antimuscarinic
dugs
Emetics
According to site of action:
a. Centrally acting: Apomorphine & Morphine
b. Peripherally acting: Mustard, Potassium tartrate

(tartar emetic) and hypertonic sodium chloride

c. Both: Ipecacuanha
Emetics –centrally acting
Apomorphine:
Given SC/IM -6mg
Causes vomiting within 15 min
In hypersensitive individuals, however, even a subtherapeutic

dose may elicit severe emesis and collapse
Vomiting is often accompanied by sedation
It should not be used if respiration is depressed
Large doses often produce restlessness, tremors, occasionally

convulsions
Sometimes may cause hypotension, syncope and coma
Emetics –peripherally acting
Mustard:
Volatile oil
Formed as a result of a reaction between a glycoside and

an enzyme in the presence of water
It is safe and easily available
Dose -1 tp in water

Sodium chloride:
Given orally
Withdraws fluid from the cells lining the stomach thus

causes irritation which causes reflex emesis
Emetics –both
Ipecacuanha (Emetine):
Acts by irritating gastric mucosa as well as through CTZ
Dried root of Cephalis ipecacuanha contains emetine
Used as syrup ipecac (15-20ml adults,10-15ml children,

5ml in infants) for inducing vomiting
Takes 15 min or more for the effect
Although apomorphine is highly effective emetic,

syrup ipecac is safer
Emetics –contraindication
All emetics contraindicated in;
Corrosive (alkali, acid) poisoning
CNS stimulant drug poisoning
Kerosine (petroleum) poisoning
Unconscious patient
List of Drugs induce vomiting
Anticancer drugs
Amiodarone
Apomorphine
Chloroquine, quinine
Diltiazem
Emetine
Ergot derivatives
Erythromycin, tetracyclines
Fluroquinolones
Metronidazole
Classification:

Antiemetics

1. Anticholinergics:

Hyoscine, Dicyclomine

2. H1 antihistaminics:

Promethazine, Diphenhydramine, Cyclizine,
Meclozine, Cinnarizine
3. Neuroleptics:

etc.

Chlorpromazine, Prochlorperazine, Haloperidol,

4. Prokinetic drugs:

Metoclopramide, Domperidone, Cisapride,
Mosapride

5. 5HT3 –Antagonists:

Ondansetron, Granisetron, Dolasetron
6. Adjuvant antiemetics:

Corticosteroids, Benzodiazepines, Cannabinoids
Anticholinergics
Hyoscine:
Most effective for motion sickness
0.2 -0.4mg oral, i.m
Brief duration of action
Produces sedation and other anticholinergic side effects
Suitable for short brisk journeys
Transdermal patch 1.5mg applied behind the pinna –to

be delivered over 3 days –suppresses motion sickness
while producing only mild side effects
Anticholinergics

Cont…

Dicyclomine:
10-20mg oral
Used for prophylaxis of motion sickness and for morning

sickness
It has been cleared of teratogenic potential
H1 antihistaminics
 Some antihistaminics are antiemetic
 They are useful mainly in motion sickness and lesser extent in

morning sickness, postoperative and some other forms of vomiting
 Their antiemetic effect appears to be based on anticholinergic,

antihistaminic and sedative properties
 Drugs available
1.

Meclizine

2.

Cyclizine

3.

Dimenhydrinate

4.

Diphenydramine

5.

Promethazine – Used in pregnancy, used by
NASA for space motion sickness
H1 antihistaminics

Cont..

All antimotion drugs are more effective when taken ½ -1

hr before commencing journey
Once sickness has started, it is more difficult to control
Neuroleptics
Potent antiemetics
Act by blocking D2 receptors in the CTZ
Antagonize apomorphine induced vomiting
Antiemetic dose is much lower than antipsychotic doses
These agents should not be administered until the cause

of vomiting has been diagnosed
Neuroleptics

Cont…

Broad spectrum antiemetic , effective in;
Drug induced and postanesthetic nausea and vomiting
Disease induced vomiting
Chemotherapy induced (mildly emetogenic)
Morning sickness: should not be used except in

hyperemesis gravidarum
Prokinetic drugs
Promote GI transit and speed gastric emptying

Drugs available

Metoclopramide
Domperidone
Cisapride
Mechanism of action of Prokinetic Drugs

D2 antagonism
5-HT4 agonism
5-HT3 antagonism
Prokinetic drugs

Cont…

Metoclopramide
 Introduced in early 1970s as a ‘gastric hurrying agent’
 Widely used antiemetic

Actions:
GIT
CNS
Prokinetic drugs
Interactions:
Hastens absorption of many drugs:
Aspirin,
Diazepam etc. by facilitating the gastric emptying

Reduces absorption of digoxin

Cont…
Prokinetic drugs

Cont…

Adverse effects:
Well tolerated
Sedation, dizziness, diarrhoea, muscle dystonias
Long term use can cause parkinsonism, galactorrhoea

and gynaecomastia
Prokinetic drugs
Uses:
Antiemetic
Gastrokinetic
Dyspepsia
Gastroesophageal reflux

disease

Cont…
Prokinetic drugs

Cont…

Domperidone:
D2 antagonist
Chemically related to haloperidol but pharmacologically related

to metoclopramide
Has lower ceiling antiemetic and prokinetic actions
Poorly crosses BBB
Rare extra pyramidal side effects
Given with levodopa or bromocriptine to counteract their dose

limiting emetic action
Prokinetic drugs

Cont…

Absorbed orally, but bioavailability is only 15% due to first

pass metabolism
Completely metabolized and excreted in urine
t ½ is 7.5hr

Side effects are less than with metoclopramide
 Dry mouth,
 Loose stools
 Headache
 Rashes
 Galactorrhoea
 Cardiac arrhythmias on rapid i.v. injection
Prokinetic drugs

Cont…

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
Prokinetic drugs

Cont…

Cisapride:
Prokinetic drug with little antiemetic property, because it lacks

D2 receptor antagonism
Gastric emptying is accelerated
LES tone is improved, esophageal peristalsis augmented
Devoid of action on CTZ and does not produce extrapyramidal

symptoms

Primary indication of cisapride has been GERD
5-HT3 antagonists
 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.
5-HT3 antagonists
 Ondansetron

32 mg / day

 Granisetron

10 µg / kg / day

 Dolasetron

Cont…

1.8 mg / kg / day

Indications
 Chemotherapy induced nausea & vomiting – given 30

min. before chemotherapy.

 Postoperative & postradiation nausea & vomiting
5-HT3 antagonists

Cont…

Adverse Effects
Excellent safety profile
Headache & constipation (common side effect)
All three drugs cause prolongation of QT interval, but

more pronounced with dolasetron.
Adjuvant antiemetics
Corticosteroids
2. Benzodiazepines
3. Cannabinoids:
1.

 Active principle of the cannabis indica
 Possesses antiemetic efficacy against moderately

emetogenic chemotherapy

Dronabinol – used as adjuvant in chemotherapy

induced vomiting. It is a psychoactive substance

Nabilone –chemotherapy induced nausea and vomiting, used
under close observation, neurological adverse effects
Thank You

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Emetics and antiemetics(VK)

  • 2. Emesis Is a protective mechanism which serves to eliminate harmful substances from the stomach and duodenum Occurs due to stimulation of the emetic center situated in the medulla oblongata Multiple pathways can elicit vomiting CTZ and NTS are the most important relay areas for afferent impulses arising from GIT, throat and other viscera CTZ is also accessible to blood borne drugs, mediators, hormones, toxins etc.,
  • 3. Pathophysiology of Emesis Emesis Cancer chemotherapy Opioids Chemoreceptor Trigger Zone (CTZ) (Outside BBB) D2, 5 HT3,,Opioid,H1, M1 Smell Sight Thought Cerebral cortex Anticipatory emesis Vomiting Centre (medulla) M1/M3, 5 HT3 & H1 Motion sickness - Vestibular nuclei M1, H1 - H1 Antagonist - DA Antagonist 5-HT3 antagonist Pharynx & GIT 5 HT3 receptors Chemo & radio therapy Gastroenteritis Antimuscarinic dugs
  • 4. Emetics According to site of action: a. Centrally acting: Apomorphine & Morphine b. Peripherally acting: Mustard, Potassium tartrate (tartar emetic) and hypertonic sodium chloride c. Both: Ipecacuanha
  • 5. Emetics –centrally acting Apomorphine: Given SC/IM -6mg Causes vomiting within 15 min In hypersensitive individuals, however, even a subtherapeutic dose may elicit severe emesis and collapse Vomiting is often accompanied by sedation It should not be used if respiration is depressed Large doses often produce restlessness, tremors, occasionally convulsions Sometimes may cause hypotension, syncope and coma
  • 6. Emetics –peripherally acting Mustard: Volatile oil Formed as a result of a reaction between a glycoside and an enzyme in the presence of water It is safe and easily available Dose -1 tp in water Sodium chloride: Given orally Withdraws fluid from the cells lining the stomach thus causes irritation which causes reflex emesis
  • 7. Emetics –both Ipecacuanha (Emetine): Acts by irritating gastric mucosa as well as through CTZ Dried root of Cephalis ipecacuanha contains emetine Used as syrup ipecac (15-20ml adults,10-15ml children, 5ml in infants) for inducing vomiting Takes 15 min or more for the effect
  • 8. Although apomorphine is highly effective emetic, syrup ipecac is safer
  • 9. Emetics –contraindication All emetics contraindicated in; Corrosive (alkali, acid) poisoning CNS stimulant drug poisoning Kerosine (petroleum) poisoning Unconscious patient
  • 10. List of Drugs induce vomiting Anticancer drugs Amiodarone Apomorphine Chloroquine, quinine Diltiazem Emetine Ergot derivatives Erythromycin, tetracyclines Fluroquinolones Metronidazole
  • 11. Classification: Antiemetics 1. Anticholinergics: Hyoscine, Dicyclomine 2. H1 antihistaminics: Promethazine, Diphenhydramine, Cyclizine, Meclozine, Cinnarizine 3. Neuroleptics: etc. Chlorpromazine, Prochlorperazine, Haloperidol, 4. Prokinetic drugs: Metoclopramide, Domperidone, Cisapride, Mosapride 5. 5HT3 –Antagonists: Ondansetron, Granisetron, Dolasetron 6. Adjuvant antiemetics: Corticosteroids, Benzodiazepines, Cannabinoids
  • 12. Anticholinergics Hyoscine: Most effective for motion sickness 0.2 -0.4mg oral, i.m Brief duration of action Produces sedation and other anticholinergic side effects Suitable for short brisk journeys Transdermal patch 1.5mg applied behind the pinna –to be delivered over 3 days –suppresses motion sickness while producing only mild side effects
  • 13. Anticholinergics Cont… Dicyclomine: 10-20mg oral Used for prophylaxis of motion sickness and for morning sickness It has been cleared of teratogenic potential
  • 14. H1 antihistaminics  Some antihistaminics are antiemetic  They are useful mainly in motion sickness and lesser extent in morning sickness, postoperative and some other forms of vomiting  Their antiemetic effect appears to be based on anticholinergic, antihistaminic and sedative properties  Drugs available 1. Meclizine 2. Cyclizine 3. Dimenhydrinate 4. Diphenydramine 5. Promethazine – Used in pregnancy, used by NASA for space motion sickness
  • 15. H1 antihistaminics Cont.. All antimotion drugs are more effective when taken ½ -1 hr before commencing journey Once sickness has started, it is more difficult to control
  • 16. Neuroleptics Potent antiemetics Act by blocking D2 receptors in the CTZ Antagonize apomorphine induced vomiting Antiemetic dose is much lower than antipsychotic doses These agents should not be administered until the cause of vomiting has been diagnosed
  • 17. Neuroleptics Cont… Broad spectrum antiemetic , effective in; Drug induced and postanesthetic nausea and vomiting Disease induced vomiting Chemotherapy induced (mildly emetogenic) Morning sickness: should not be used except in hyperemesis gravidarum
  • 18. Prokinetic drugs Promote GI transit and speed gastric emptying Drugs available Metoclopramide Domperidone Cisapride
  • 19. Mechanism of action of Prokinetic Drugs D2 antagonism 5-HT4 agonism 5-HT3 antagonism
  • 20. Prokinetic drugs Cont… Metoclopramide  Introduced in early 1970s as a ‘gastric hurrying agent’  Widely used antiemetic Actions: GIT CNS
  • 21. Prokinetic drugs Interactions: Hastens absorption of many drugs: Aspirin, Diazepam etc. by facilitating the gastric emptying Reduces absorption of digoxin Cont…
  • 22. Prokinetic drugs Cont… Adverse effects: Well tolerated Sedation, dizziness, diarrhoea, muscle dystonias Long term use can cause parkinsonism, galactorrhoea and gynaecomastia
  • 24. Prokinetic drugs Cont… Domperidone: D2 antagonist Chemically related to haloperidol but pharmacologically related to metoclopramide Has lower ceiling antiemetic and prokinetic actions Poorly crosses BBB Rare extra pyramidal side effects Given with levodopa or bromocriptine to counteract their dose limiting emetic action
  • 25. Prokinetic drugs Cont… Absorbed orally, but bioavailability is only 15% due to first pass metabolism Completely metabolized and excreted in urine t ½ is 7.5hr Side effects are less than with metoclopramide  Dry mouth,  Loose stools  Headache  Rashes  Galactorrhoea  Cardiac arrhythmias on rapid i.v. injection
  • 26. Prokinetic drugs Cont… 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
  • 27. Prokinetic drugs Cont… Cisapride: Prokinetic drug with little antiemetic property, because it lacks D2 receptor antagonism Gastric emptying is accelerated LES tone is improved, esophageal peristalsis augmented Devoid of action on CTZ and does not produce extrapyramidal symptoms Primary indication of cisapride has been GERD
  • 28. 5-HT3 antagonists  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.
  • 29. 5-HT3 antagonists  Ondansetron 32 mg / day  Granisetron 10 µg / kg / day  Dolasetron Cont… 1.8 mg / kg / day Indications  Chemotherapy induced nausea & vomiting – given 30 min. before chemotherapy.  Postoperative & postradiation nausea & vomiting
  • 30. 5-HT3 antagonists Cont… Adverse Effects Excellent safety profile Headache & constipation (common side effect) All three drugs cause prolongation of QT interval, but more pronounced with dolasetron.
  • 31. Adjuvant antiemetics Corticosteroids 2. Benzodiazepines 3. Cannabinoids: 1.  Active principle of the cannabis indica  Possesses antiemetic efficacy against moderately emetogenic chemotherapy Dronabinol – used as adjuvant in chemotherapy induced vomiting. It is a psychoactive substance Nabilone –chemotherapy induced nausea and vomiting, used under close observation, neurological adverse effects

Notes de l'éditeur

  1. Lower esophageal sphincter (LES) tone is increased and GER is opposed Also increases intestinal peristalsis to some extent CNS: Acts on the CTZ, blocks apomorphine induced vomiting No neuroleptic action GIT: Prominent effect on upper g.i.t; increases gastric peristalisis Speeds gastric emptying, specially if it was slow