Untitled

\
 The act of vomiting and the sensation of

nausea that accompanies it are protective
reflexes that serve to rid the stomach and
intestine of toxic substances and prevent
their further ingestion
 Apomorphine– CTZ ( D2 agonist)
 Ipecacuanha—CTZ & reflexly
 Powdered mustard suspension & Strong salt solution.
 Use: In some cases of poisoning

1. Corrosive poisoning ( Acid, Alkali ):
2. CNS stimulant drugs poisoning:
3. Kerosine poisoning:
4. Unconcious patient:
5. Morphine & Phenothiazine poisoning:

Pathophysiology of Emesis
Cancer chemotherapy
Cerebral cortex
Opioids Smell
Sight Anticipatory emesis
Thought
Chemoreceptor Vomiting Centre Vestibular
Trigger Zone (medulla)
Motion nuclei
(CTZ) sickness
Muscarinic, 5 HT3 & Muscarinic
(Outside BBB) Histaminic H1,CB1 Histaminic H1
Dopamine D2
5 HT3,,Opioid Chemo & radio therapy
Receptors, NK1 Gastroenteritis
Pharynx & GIT

5 HT3 receptors
Group of drugs used as antiemetics
 Serotonin 5 HT3 Antagonists
 Dopamine D2 Antagonist
 Anticholinergics
 H1 Antihistaminics
 Cannabinoids
 Neurokinin-1 antagonists
SEROTONIN 5 HT3 ANTAGONIST
 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.
DRUGS AVAILABLE
 Ondansetron 32 mg / day
 Granisetron 10 g / kg / day
 Dolasetron 1.8 mg / kg / day
 Palonosetron
INDICATIONS
 Chemotherapy induced nausea & vomiting – given
30 min. before chemotherapy.
 Postoperative & postradiation nausea & vomiting
ADVERSE EFFECTS
 Excellent safety profile
 Headache & constipation
 All three drugs cause prolongation of QT interval,

but more pronounced with dolasetron.
DOPAMINE D2 ANTAGONIST
 Antagonise 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.
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.
Metoclopramide: Therapeutic Use
1) Nausea and vomiting that often accompany GI

dysmotility syndromes.
2) Gastroesophageal reflux disease (symptomatic
relief but not healing of esophagitis).
3) Gastroparesis where it improves gastric
emptying.
4) Diagnostic procedures such as intestinal
intubation or contrast radiography of the GI
tract.
5) Postoperative ileus
6) Persistent hiccups
PHENOTHIAZINES & BUTYROPHENONES
( D2 )
 Phenothiazines
Prochlorperazine ( Vertigo with vomiting )

 Phenothiazines are antipsychotics with potent
antiemetic property due to D2 antagonism in
CTZ & antihistamine activity.
 Butyrophenone ( D2 )
Droperidol, Haloperidol
 Droperidol used for postop. nausea & vomiting,
but cause QT prolongation.
H1 ANTIHISTAMINICS
 Effective drugs for motion sickness
 Anticholinergic, Antihistaminic, Sedative
 Drugs available
Meclizine ( LA, sea sickness )

Cyclizine
Dimenhydrinate
Diphenydramine
Promethazine – Used in pregnancy, used by
NASA for space motion sickness
ANTICHOLINERGICS
 Scopolamine (hyoscine) – used as transdermal

patch for motion sickness.
 Dicyclomine– Motion & Morning sickness
CANNABINOIDS ( CB1)
 Dronabinol – used as adjuvant in chemotherapy
induced vomiting.It is a psychoactive substance
 Nabilone
Corticosteroids have antiemetic properties
Mechanism of action: possibly by suppressing
peritumoral inflammation and prostaglandin
production.
Use: to enhance efficacy of 5HT3 receptor
antagonists in the treatment of chemotherapy-
induced vomiting.
-- also reduce certain S/E of primary antiemetic
 Uses:
 Benzodiazepines such as diazepam/
lorazepam are used prior to the initiation of
chemotherapy to reduce anticipatory
vomiting or vomiting caused by anxiety.
MOA
Act as Antiemetic: Selectively block NK1 receptor in
area postrema.
No effect on Serotonin , Dopamine or Corticoid
receptors
 Non peptide, selective, Neurokinin type 1 (NK 1)
receptors antagonist
 Block substance P from binding to NK1 receptor
 Broader spectrum and activity in delayed emesis (In
Preclinical studies)
 Augment the antiemetic activity of 5HT3 receptor
antagonists and dexamethasone
 Inhibit both acute and delayed Cisplatin induced
vomiting
Uses
Used in combination with 5HT3 antagonists &
Corticosteroids for prevention of acute & chronic
nausea and vomiting from Cancer chemotherapy
A/Es
 Fatigue, dizziness & diarrhoea.
 Enzyme inhibition
 Metabolized by CYP3A4 & may inhibit metabolism of many
anticancer drugs (Docetaxel, Paclitaxel, Etoposide,
Vinblastine, Imatinib) ---- ↑ levels --- toxicity.
 Metabolism of Aprepitant may be inhibited by
Ketoconazole, Ciprofloxacin, Clarithromycin, Nafazodone,
Ritonavir, Nelfinavir, Verapamil & Quinidine)
 Aprepitant ↓ INR in patients taking warfarin.
Therapeutic Uses of Anti-emetics
 Motion sickness: Hyoscine
 Vestibular disorders( Menieres, disease): Cinnerazine
 Vomiting due to Uremia, Radiation, Viral gastro enteritis,

Liver disease, Migraine, Prochlorperazine ,
Metroclopramide
 Vomiting due to pregnancy ( hyperemesis gravidarum),

Meclizine with vit. B6 (Navidoxine)
 Vomiting due to Cytotoxic Anticancer drugs: 5HT3
Antagonists Metroclopramide,
Cannabinoids, corticosteroids , Aprepitant
 Anticipatory Vomiting due to Cytotoxic

Anticancer drugs. Benzodiazepines (Diazepam)
 Post Operative Vomiting: Metoclopramide ,

Prochlorperazine , Dimenhydrinate, 5HT3 Antagonists
(Ondensetron)
 Cisplatin
- Acute emesis NK1 + 5-HT3 + DEX
- Delayed emesis NK1 + DEX or

DEX + MTC or
DEX + 5-HT3
 Moderately emetogenic chemotherapy

- Acute emesis 5-HT3 + DEX NK1
- Delayed emesis NK1 or DEX

 1. Which of the following drug is not used for
moton sickness?
 •Metoclopramide
 • Cyclizine
 • Cinnarizine
 • Scopolamine
 A
 Ondansetron acts by inhibitng which of the
following
 receptors
 • 5-HT1
 • 5-HT2
 •5-HT3
 • 5-HT4
 C
 3. Which of the following receptor is not
involved in nausea and vomitng?
 • Dopamine
 • Acetylcholine
 • Histamine
 All of the above
 B
 Which drug work by blocking serotonin
receptor in the GI tract, vomitng center,
and CTZ?
 • Meclizine
 • Metoclopramide
 •Ondansetron
 • Droperidol
 C
 All are antiemetics except :
a) Domperidone
b) Ondensetron
c) Phenazocine
d) Cyclizine
 C
 . Which one is NK1 receptor antagonist?
 a. Aprepitant
 b. Fosaprepitant
 c. a$b
 d. None
 A
 What are the side effects of
Metoclopramide?
 a. Muscle dystonia
 b. Dizziness
 c. Loose motion
 d. All of above
 D
 Drugs promote g.i.t transit and speed
gastric emptying by enhancing coordinated
propulsive motility.
 a. Prokinetic drugs
 b. Antihistaminics
 c. Anticholinergics
 d. Corticosteroids
 A
 . Which are the examples of
antihistaminics used as antiemetics?
 a. Promethazine
 b. Diphenhydramine
 c. Dimenhydrinate
 d. All of above
 D
Thank you

Untitled

Uploaded by

Copyright:

Available Formats

Untitled

Uploaded by

Document Information

Original Description:

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Untitled

Uploaded by

Copyright:

Available Formats

\

 The act of vomiting and the sensation of

 Ipecacuanha—CTZ & reflexly

 Powdered mustard suspension & Strong salt solution.

 Use: In some cases of poisoning

2. CNS stimulant drugs poisoning:

5. Morphine & Phenothiazine poisoning:

Pharynx & GIT

 Even though 5 HT3 receptors are present in

 Excreted by liver & kidney

 No dose reduction in renal insufficiency but needed

 Excellent safety profile

 Headache & constipation

 All three drugs cause prolongation of QT interval,

Metoclopramide 2.5 mg b.d

 Metoclopramide crosses BBB but domperidone

 As CTZ is outside BBB both have antiemetic

1) Nausea and vomiting that often accompany GI

Prochlorperazine ( Vertigo with vomiting )

 Anticholinergic, Antihistaminic, Sedative

Meclizine ( LA, sea sickness )

 Scopolamine (hyoscine) – used as transdermal

 Motion sickness: Hyoscine

 Vestibular disorders( Menieres, disease): Cinnerazine

 Vomiting due to Uremia, Radiation, Viral gastro enteritis,

 Vomiting due to pregnancy ( hyperemesis gravidarum),

 Anticipatory Vomiting due to Cytotoxic

 Post Operative Vomiting: Metoclopramide ,

- Delayed emesis NK1 + DEX or

 Moderately emetogenic chemotherapy

- Delayed emesis NK1 or DEX

You might also like