Antiemetic

drugs
Dr. Jatin Dhanani

Causes of vomiting

Food intolerance,
Viral & Bacterial infection,
Motion sickness
Post operative
Pain
Shock
Drug induced
Radiation
Disturbances of the equilibrium or middle ear
affection

Pathophysiology of
3
vomiting
2

4
1

Emetics

Substances which produce vomiting

Required when an undesirable substance

(poison) has been ingested

Home based ?????

Emetic drugs

Apomorphine
Ipecacuanha

Apomorphine

Semi synthetic derivative

of morphine
directly stimulate CTZ or
VC
Given IM or SC (not
orally) 6 mg
Induces vomiting in 5
-10min
CNS & Respiratory
depressant

Ipecacuanha
Irritate gastric & duodenal
mucosa stimulate
afferent fibers of vagus
nerve Stimulate the VC
Contains two alkaloidsemetine & cephaeline
Used as syrup ipecac
Produces effect in 15 min
Dose
Infants = 5 ml
Children = 10-15ml
Adults = 15-20ml

Contraindications of
emetics

Corrosive poisoning
CNS stimulant drug poisoning
Kerosene poisoning
Unconscious patients
Morphine poisoning

Classification Antiemetic
drugs
Selective 5-HT
H antihistamines
3

Antagonists

Promethazine,
Dimenhydrinate &
Diphenhydramine,
cyclizine, Meclizine,
Cinnarizine

Muscarinic
Antagonist
Hyoscine (Scopolamine),
dicyclomine

Ondansetron,
Granisetron,
Palonosetron &
Dolasetron

Prokinetic
agents
Metoclopramide,
domperidone, cisapride,
mosapride, tagaserod

D2 Antagonists
(neuroleptics)
Haloperidol, chlorpromazine,
prochlorperazine

Cannabinoids
Dronabinol, Nabilone

Neurokinin-I Antagonist

Adjuvant
antiemetics

Aprepitant (oral formulation),

Fosaprepitant (IV formulation)

Glucocorticoids
(Dexamethasone,
Methylprednisolone)
Benzodiazepines
(Diazepam, Lorazepam)

Prokinetic agents

Metoclopramide
Domperidone
Cisapride, Mosepride
tegaserod

Drugs which promote gastrointestinal transit

and speed gastric emptying

Metoclopramide
Chemistry: Substituted Benzamide
MOA: Dopamine D2 receptors antagonist
It is potent Antiemetic & Prokinetic agent
As Antiemetic

Blocks D2 receptors in CTZ of the medulla (area postrema)

Blocks 5-HT3 receptors in CTZ (at high dose)

As Prokinetic agent

1.
2.

3.

5-HT4 agonistic action in gut in excitatory ENS of intrinsic

PAN (main mech.)
Others
Blocks D2 receptor in GIT increase Ach release,
Blockade of 5-HT3 receptor in inhibitory ENS of
intrinsic PAN, and also
Directly sensitize muscarinic receptor of smooth muscle of
GIT --- motility

Pharmacokinetics

Rapidly absorbed from GIT after oral administration

Undergoes a high degree first pass metabolism
Approx. onset of action is 30 60 min, 10 min and
2 min after oral, IM, and IV administration So,
route selected according to severity
Excreted in the urine as free and as metabolites.
Also excreted in the breast milk.
DOSE: 10-20 mg orally or IV every 6 hrs

Uses metoclopramide

As Antiemetic: in various type of vomiting

postoperative, drug induced, disease associated &

radiation sickness

As prokinetic:

During emergency general anesthesia (food taken less

than 4 hr before)
To relieve postvegotomy or diabetic gastric stasis
To facilitate duodenal intubation
GERD: adjuvant to acid suppressant therapy

Dyspepsia and other functional GI disorders

Hiccups

Adverse Effects

Extrapyramidal reactions

facial and skeletal muscle spasms- Restlessness, Dystonias,

Parkinsonian symptoms (Occulogyric crises)
More common in young and very old
Occurs shortly after staring treatment & subside with in 24
hours of stopping the drug

Bowel upsets, Diarrhoea

Drowsiness, fatigue, dizziness, restlessness, anxiety
Galactorrhoea, Gynecomastia, impotence and
menstrual disorders due to increased prolactin
levels

Trimethobenzamide
Substituted Benzamide
Antiemetic like Metoclopramide.
D2 Antagonist & mild anti- histaminic activity
DOSE: 250mg orally,
200mg rectally,
200mg IM

Domperidone

Only blocks D2 in CTZ

Does not cross BBB

Used along with Levodopa and bromocriptine

(prevent peripheral side effect, without affecting its
efficacy)
No EPS

Use: as antiemetic, prokinetic agent & for post

partum lactation stimulation
A/E: less than metoclopramide

Dry mouth, loose stools, headache,

galactorrhoea
cardiac arrhythmia on rapid iv injection

rashes,

Cisapride

MOA: 5-HT4 agonist (main) and weak 5-HT3

antagonist, while no affinity on D2 receptor

Actions

Restore and facilitates motility throughout the GIT

including colon
LES tone improved
Promote cAMP-dependent Cl- secretion in colon
increase water content of stool

Indication

GERD
Nonulcer dyspepsia, impaired gastric emptying,
chronic constipation

A/E
Abdominal cramp and diarrhoea
Dizziness
Rise in serum transaminase level
Torsades de pointes and ventricular arrhythmia (at
high conc./ with CYP 3A4 inhibitors)

Mosapride

Not caused ventricular arrhythmia

Tegaserod

No 5-HT3 action
Less efect on LES tone & mainly increase colonic
motility, gastric emptying and intestinal transit
Indication: constipation predominant irritable
bowel syndrome

5-HT3 antagonists

Mechanism of action

Ondensetron
Granisetron
Dolasetron
Palnosetron

Blocks Peripheral 5HT3 receptors on intestinal vagal

and spinal afferent fibers (main)
Also block central 5HT3 receptors in Vomiting center &
CTZ

Antiemetic action

restricted to emesis caused by vagal stimulation (eg

post op) & chemotherapy/ radiotherapy
Also effective in vomiting with drug overdose,
uremia and certain neurological injuries

Pharmacokinetics 5-HT3 blockers

High first pass metabolism

t1/2 : 4-9 hrs (Ondansetron, Granisetron & Dolasetron)
40 hrs (Palonosetron)
Given once or twice daily orally or intravenously
No dose reduction in renal insufficiency but needed
in hepatic insufficiency (Ondansetron)

Dose: (ondansetron)
Chemotherapy: 8 mg IV 15min hr b/f therapy
f/b 2 dose 4 hr apart f/b 8 mg bid for 3-5 days
Post operative: 4-8 mg IV b/f induction f/b 8 hrly

Adverse Effects

Excellent safety profile

Headache & Dizziness
Mild constipation or diarrhea and abdominal
discomfort
Rashes and allergic reaction
Prolongation of QT interval (dolasetron)

H1antihistamines & Muscarinic

Antagonists

Most effective drugs for motion sickness

MOA
H1 antihistaminics

Muscarinic antagonists
Promethazine
Anticholinergic, H1 antagonist
& sedative
Hyoscine
& Dicyclomine
Diphenhydramine
properties
Dimenhydrinate
Produce specific depression of conduction in
Doxylamine
Cyclizine,
meclizine
vestibulocerebellar
pathway via cranial nerve VIII
Cinnarizine

rich in Cholinergic M1 & Histamine H1receptors

Hyoscine

Most effective drug for motion sickness

Dose: 0.2 0.4 mg oral or IM
1.5 mg Transdermal patch for 3 days

Dicyclomine (10-20 mg)

For motion and morning sickness

Promethazine, diphenhydramine,
dimenhydrinate

Antihistaminics with anticholinergic properties

Added with metoclopramide

Doxylamine

Widely used in morning sickness: along with

pyridoxine

Cyclizine & meclizine

Less sedative and less anticholinergic

Meclizine long acting (use in seasickness)

Cinnarizine

Antivertigo drug also useful in motion sickness

Inhibits the influx of Ca ++ ion from endolymph to
vestibular sensory cells

Neuroleptics

Chlorpromazine
Prochlorperazine
Haloperidol

Mechanism of Action

Acts by blocking D2 receptor in the CTZ

Additional antimuscarinic and antihistaminic
property

Potent and broad spectrum antiemetic

agents

Drug induced and post anesthetic N & V

Disease induced: uremia, liver diseases,
migraine, gastroenteritis
Malignancy and cancer chemotherapy induced
vomiting
Radiation sickness (less effective)
Hyperemesis gravidarum
Not use in motion sickness

Problems

High potential of side effects like muscle dystonia,

sedation
Not use widely

Cannabinoids

semisynthetics
MOA:

activate CB1 receptors at vomiting center or higher

center

Ph.K:

Dronabinol
Nabilone

complete absorption on oral adm, significant 1st pass

effect, metabolites excreted slowly over days to weeks
in faeces & urine

Use:

Cancer chemotherapy induced N & V with

Phenothiazines synergistic
Appetite stimulant in cachectic/AIDS patients

Neurokinin-1 (NK1 )Antagonists

Aprepitant,
Fosaprepitant

MAO:

Non peptide, selective, NK 1 receptors antagonist

Block substance P from binding to NK1 receptor

Augment the antiemetic activity of 5HT3 receptor

antagonists and dexamethasone
Broader spectrum and activity in delayed emesis
Inhibit both acute and delayed Chemotherapy
induced N & V

Adjuvant antiemeticsDexomethasone

Glucocorticoids

As an adjuvant to the other antiemetic drugs

during cancer chemotherapy
Acts by ing inflammation and PG production at
peritumor areas
Use in refractory cases only

Benzodiazepines

Methylprednisolone

Diazepam
Lorazepam

Action is based on sedative property

Weak antiemetics
Use as an adjuvant to other antiemetic

Thank You