This document discusses emetics and antiemetics. It describes the process of emesis and the neurotransmitters involved like serotonin, acetylcholine, dopamine, and histamine. It discusses the vomiting center in the brainstem and various emetic and antiemetic drugs. Emetic drugs discussed include apomorphine, ipecacuanha, and mustard. Antiemetic drug classes covered are anticholinergics, H1 antihistamines, neuroleptics, prokinetic drugs, 5-HT3 antagonists, and NK1 receptor antagonists. Individual drugs like ondansetron, metoclopramide, domperidone, and aprepitant are described in detail

1. Emetics And Antiemetics
By Dr. Chintan Doshi

2. •EMESIS

3. Introduction
Act of emesis and the sensation of nausea that
accompanies it generally are viewed as protective
reflexes that serve :
• to rid the stomach and intestine of toxic substances
• prevent their further ingestion

4. Contd.
Complex process consists of
• Pre-ejection phase
– gastric relaxation
– retro peristalsis
• Retching
– rhythmic action of respiratory muscles preceding
vomiting and
– consisting of contraction of abdominal and intercostal
muscles and diaphragm against a closed glottis

5. Contd.
• Ejection
– intense contraction of the abdominal muscles
– relaxation of the upper esophageal sphincter

6. Neurotransmitters Involved
• Serotonin via 5HT3 receptors
• Acetylcholine via M receptors
• Dopamine via D2 receptors
• Histamine via H1 receptors

7. • VOMITING CENTER
– in the lateral reticular formation of the mid-
brainstem

8. Contraindications
Corrosive poisoning
CNS stimulant drug poisoning
Kerosene poisoning
Unconscious patients
Morphine poisoning

10. Emetic Drugs - Uses
Acute cases of poisoning
Alcoholic intoxication
 Removal of foreign bodies from the oesophagus
To remove the bronchial secretion in cases of bronchitis
To relax spasm of the pharyngeal muscles in cases of
spasmodic laryngitis.

11. Contraindications
Hernias
Peptic ulcer
Hypertension
Pulmonary TB
Pregnancy
Uraemia

12. Emetic Drugs
• Centrally acting: Apomorphine
• Reflexly acting: Ipecacuanha
• Locally acting:
– Alum,
– Sodium Chloride (Conc. .Solution)
– Mustard Powder

13. Contd.
• Other Drugs as Adverse Effect:
– Morphine,
– Digitalis,
– Emetine,
– Aspirin,
– Quinine &
– Anticancer drugs

14. •ANTIEMETIC DRUGS

15. Classification
Group Name
Anticholinergic Hyoscine,Dicyclomine
D2 Blockers(Neuroloeptics) Chlorpromazine, Procholrperazine,
Trifluoperazine
Prokinetic drugs Metoclorpramide,Domperidone,
Cisapride, Mosapride, Itopride
NK1 antagonist Aprepitant,Fosaprepitant
5 HT 3 antagonist Ondansetron,Granisetron,Palonosetr
on

16. Group Name
H1 antihistaminics Promethazine,
diphenhydramine,
demethhydrinate, Doxylamine
Adjuvant Dexamehasone,
benzodiazapine, Dronabinol

17. Anticholinergics
Hyoscine
• USE: Motion sickness
• Brief duration of action:4-6 hrs
• S/E: Sedation, dry mouth
• Dose:
– 0.2 to 0.4 mg oral or i.m.
– Transdermal patch: 1.5 mg applied behind pinna 4
hrs before journey gives protection for 3 days

18. Contd.
Dicyclomine
• Use: Motion sickness
• Dose: 10-20 mg oral

19. H1 Antihistaminics
Promethazine
• Use: Motion sickness, Postoperative nausea
and vomiting
• Duration of action: 4 to 6 hrs
• S/E: sedation, dry mouth
• Blocks extrapyramidal side effect of
metoclopramide and enhance its action

20. Contd.
Doxylamine
• Use: Morning sickness In combination with
pyridoxine
• Oral absorption Slow
• t1/2 : 10 hr
• S/E: Dry mouth, vertigo, drowsiness
• Dose: 10-20 mg oral at bed time

21. Contd.
Meclozine
• Less sedative and longer acting
• Use: Sea sickness
• Duration of action: 24 hrs

22. Contd.
Cinnarizine:
• Use: motion sickness
• Has antihistaminic, anticholinergic,
antiserotonin properties
• Inhibits influx of Ca+2 from endolymph into
vestibular sensory cell

23. Neuroleptics
M/O:
• Acts by blocking D2 receptor in CTZ
• Additional H1 antihistaminic action and
antimuscarinic action
USE:
a. Drug induced and postoperative nausea and
vomiting
b. Disease induced vomiting: gastroenteritis,
migraine, uremia

24. Contd.
c) Malignancy associated and cancer
chemotherapy induced vomiting
d) Radiation sickness
Side effects
• EPS
• sedation
• postural hypotension
• anticholenergic side effects

25. Prokinetic Drugs
METOCLOPRAMIDE
• Chemistry: Substituted Benzamide,Chemically related
to Procainamide
• MOA: Dopamine D2 receptors antagonist
It is potent Antiemetic & Prokinetic agent
As Antiemetic
– It has potent Antiemetic & antinausea effect.
– Blocks D2 receptors in CTZ of the medulla
– Higher dose blocks 5HT3 receptor

26. Contd.
As Prokinetic agent
– It can selectively stimulate gut motor function.
– Blocks D2 receptor in GIT & blocks the normal
inhibitory effect of Dopamine on cholinergic
smooth muscle stimulation--- ↑ motility.
– 5HT4 agonism: ↑ Ach and ↑ motility.

27. Uses - Metoclopramide
Potent antiemetic controls / reduces vomiting due to
• Uremia
• Radiation
• Viral gastro enteritis, hepatic-biliary disease
• Anticancer drugs
• Migraine
• Post operatively & pre-operatively

28. As prokinetic agent useful in
 GERD
Only symptomatic relief. May be combined with anti- secretory
agents in refractory cases.
 Impaired GI emptying
o After surgery (vagotomy , antrectomy)
o Diabetic gastropresis.
 To promote advancement of nasoenteric feeding tube from
stomach to intestine.
 Non-ulcer dyspepsia
Only symptomatic relief in chronic dyspepsia
 Emergency general anesthesia and patient has taken food less
than 4 hrs before

29. Pharmacokinetics
• Rapidly absorbed orally
• Act in ½ hr after orally and 10 min after i.m. and 2
min after i.v. injection
• Partly conjugated in liver
• Excreted in urine
• t1/2 : 4-6 hrs

30. Adverse effect
• Sedation, dizziness, loose stools
• Acute muscle dystonias
• Parkinsonism, tardive dyskinesia
• Galactorrhoea, gynecomystia
• Methemoglobinemia: occasionally in premature
and full-term neonates

31. Domperidone
• D2 receptor antagonist
• Chemically: haloperidol
• Pharmacologically: metoclopramide
• Not cross blood brain barrier so extrapyramidal side
effect are rare
• Oral bioavailability-15% due to first pass metabolism
• t1/2 : 7.5 hr

32. Contd.
Adverse effects
• Loose stools, dry mouth
• Headache
• Galactorrhoea
• Rashes
• Cardiac arrhythmia on rapid i.v. injection

33. Cisapride
M/O:
• 5 HT4 agonist: ↑ Ach and ↑ motility
• Weak 5 HT3 blocking action
Pharmacokinetics
• Inactivated via CYP3A4
• t1/2 : 10 hrs

34. Contd.
Side effects
 Prolongs Q-Tc interval and cause torsades de
pointes /ventricular fibrillation
 Serious ventricular arrhythmia and death
among patients who take CYP3A4 inhibitors

35. Itopride
• D2 antagonist and anti-chE activity
• Low affinity for 5 HT4 receptor
• No prolongation of Q-Tc interval
• Metabolized by flavin monooxygenase
Side effects:
• Diarrhoea, abdominal pain, headache
• Galactorrhoea and gynecomastia rarely

36. Prucalopride
• Safe analogue of cisapride
• Highly selective for 5 HT4 receptor
• Use: severe constipation
• No prolongation of Q-Tc interval

37. • Mosapride, zacopride and renzapride are newer
congner
• No prolongation of Q-Tc interval
• Other properties are same as cisapride

38. 5-HT3 Receptor Antagonists
DRUG
CHEMICAL
NATURE
RECEPTOR
INTERACTIONS
t1/2 DOSE (IV)
Ondansetron
Carbazole
derivative
5-HT3 antagonist and
weak 5-HT4 antagonist
3.9 h 0.15 mg/kg
Granisetron Indazole 5-HT3 antagonist 9-11.6
h
10mcg/kg
Dolasetron Indole moiety 5-HT3 antagonist 7-9 h 1.8 mg/kg
Palonosetron Isoquinoline 5-HT3 antagonist;
highest affinity for 5-HT3
receptor in this class
40 h 0.25 mg

39. Contd.
M/O:
 Act as anti-emetic by Selectively blocking
central 5HT3 receptors in Vomiting center &
CTZ &
 by blocking periphery 5HT3 receptors on
intestinal vagal and spinal afferent fibers

40. USES
• Prevention of acute chemotherapy induced Nausea &
vomiting
• Delayed CINV: Palonosetron
• To prevent & treat post operative & post radiation Nausea &
vomiting
• Hyperemesis of pregnancy
• Granisetron is available as a transdermal formulation that is
applied 24-48 hours before chemotherapy

41. Adverse effects
• Diarrhoea, headache and lightheadedness
• Hypotension, chest pain and allergic reaction
on rapid i.v. injection
• Prolong Q-Tc interval by Dolasetron

42. NK1 receptor antagonist
Aprepitant
 FDA approved on March 2003
 NK1 receptor antagonist that blocks action of
substance P
 USE:
– delayed CINV with single or repeated courses of
highly emetogeneic chemotherapy
– improve the efficacy of standard anti-emetic
regimens

43. MCQ
• Ondansetron acts by:
• (a) Acting on CTZ
• (b) 5-HT3 antagonism
• (c) D1 and D2 receptor antagonism
• (d) Increasing GIT motility
• (e) Blocking cholinergic receptors

44. • Which of the following prokinetic drugs
produces extrapyramidal side effects?
• (a) Metoclopramide
• (b) Cisapride
• (c) Domperidone
• (d) All of the above

45. • Which of the following drugs is not used for
motion sickness
• (a) Metoclopramide
• (b) Cyclizine
• (c) Cinnarizine
• (d) Scopolamine

46. • Antiemetic used in vomiting induced by
anticancer drugs is:
• (a) Ondansetron
• (b) Cisapride
• (c) Metoclopramide
• (d) Trifluopromazine

47. • Which of the following is the most potent
5HT3 antagonist?
• (a) Ondansetron
• (b) Granisetron
• (c) Dolasetron
• (d) Palonosetron

48. • All of the following are true for
metoclopramide except:
• (a) Chemically related to procainamide
• (b) Speeds gastric emptying
• (c) Stimulates chemoreceptor trigger zone
• (d) Blocks D2 receptors

49. • Which of the following 5-HT receptors play
an important role in causing emesis?
• (a) 5HT1
• (b) 5HT2A/2C
• (c) 5HT3
• (d) 5HT4