The document discusses antiemetics and their mechanisms of action. It summarizes that antiemetics act on the vomiting center in the brainstem to prevent nausea and vomiting. The vomiting center receives input from various areas and transmits signals via neurotransmitters like serotonin, dopamine, acetylcholine and substance P. Common antiemetic drug classes include 5-HT3 antagonists, antihistamines, neurokinins, cannabinoids and corticosteroids. Metoclopramide is highlighted as having prokinetic effects via D2 antagonism while ondansetron is an effective 5-HT3 antagonist for chemotherapy-induced nausea.

1. DR. PRUTHA PILANKAR
DEPARTMENT OF PHARMACOLOGY

2.  Drugs used to prevent or suppress vomiting.

3. •Vomiting is a complex process that appears to be
coordinated by a central vomiting center in the
lateral reticular formation of the mid brainstem

4. The vomiting center receives information from
1. The CTZ(Chemoreceptor trigger zone) and
NTS(Nucleus tractus solitarius)
2. The gut, principally by the vagus nerve
3. The cerebral cortex (particularly in anticipatory
nausea or vomiting, pain, sight, smell)
4. The vestibular apparatus (in motion sickness)
via cerebellum, receptor involved are M1 andH1
•Relay information to the vomiting center to trigger
nausea and vomiting

5. •Vomiting(emetic) center is adjacent to
•Chemoreceptor trigger zone (CTZ) in
the area postrema on the floor of the
fourth ventricle and lack blood-brain
barrier
•Nucleus tractus solitarius (NTS)
posterolateral region of the medulla

6. 1. Serotonin (5HT3)
2. Dopamine (D2)
3. Acetylcholine (muscarinic M1)
4. Neurokinin (NK1)
5. Cannabinoid (CB1)
6. Opioids
1. Histamine (H1)
2. Acetylcholine (M1)
3. Serotonin (5HT3)
4. Dopamine (D2)
CTZ
NTS
Antiemetics generally are classified according
to the predominant receptor on which they
are proposed to act

7. Higher centres fear, emotion, smell sight
Emetic centre cerebellum inner ear
NTS CTZ
5HT3, D2, 5HT3, D2,M1
M1,HI
Stomach SI 5HT3
Toxins, Drugs, Irritants
3
1
4
2

8. 1. Prokinetic drugs
 Metoclopramide
antiemetic + prokinetic
 Domperidone
 Mosapride
only prokinetic
 Itopride
 Cisapride banned
Prolongs QTc interval ----- ventricular arrhythmias

9. 2. 5HT3 antagonism
 Ondansetron
 Granisetron
 Palonosetron
 Ramosetron

10. 3. Anticholinergics Hyoscine
Dicyclomine
4. H1 antihistaminics Promethazine
Diphenhydramine
Dimenhydrinate
Doxylamine
Meclizine
Cinnarizine

11. 5. Neuroleptics: Chlorpromazine
Prochlorperazine
6. NK1 receptor antagonist:-Aprepitant , Fosaprepitant
7. Cannabinoids :- Dronabinol, Nabilone
8. Adjuvant antiemetics :- Dexamethasone,
Benzodiazepines.

12.  Promote GI transit &
speed gastric emptying by
enhancing coordinated propulsive movements.

13.  Introduced in 1970s as a ‘gastric hurrying agent’.

14. 1. GIT
 Dopamine is an inhibitory neurotransmitter
in the GIT.
 Delays gastric emptying
 Relaxes LES.

15. a. D2 antagonism in GIT
Prominent effect on upper GIT
Speeds gastric emptying
1. Increases gastric peristalsis
2. Relaxes pylorus & first part of the duodenum
3. Lower esophageal sphincter tone is increased &
gastroesophageal reflux is opposed.

16. b. 5HT4 agonism in GIT
Enhances ACH release from myenteric motor
neurons, thereby increasing GI motility.
C. 5 HT3 antagonism
1. Block 5HT3 rs present on inhibitory myenteric
interneurons & enhance AcH release, thereby
increasing GI motility.

17. 2. CNS
Effective antiemetic
Blocks D2 rs in the CTZ
Block 5HT3 rs in NTS & CTZ

18.  Rapidly absorbed orally.
 Crosses BBB.
 Metabolised in liver excreted in urine
 t½ 3-6 hours
 Onset of action
oral 30 mins
IM 10 mins
IV 2 mins

19. 1. Abolishes the therapeutic effect of levodopa
by blocking DA receptor.
2. Hastens absorption of aspirin, diazepam
by facilitating gastric emptying.
3. Reduces absorption of digoxin, cimetidine.

20.  Sedation
 Diarrhoea
 Dystonia
 Long term
Parkinsonism,
Galactorrhoea,
Gynaecomastia

21. Dose
10 mg tds oral or IM

22. 1. Antiemetic
a. Vomiting d/t GI disorder
b. Postoperative vomiting
c. Drug induced vomiting
d. Disease associated vomiting
e. Radiation sickness vomiting
f. Chemotherapy induced vomiting

23. 2. Gastrokinetic to accelerate gastric emptying
a. When emergency GA has to be given &
pt has taken food less than 4 hours before.
b. To relieve post vagotomy or diabetic gastro paresis
associated gastric stasis.

24.  D2 receptor antagonist.
 Prokinetic action is d/t D2 rs antagonism in GIT.
 Antiemetic action is d/t D2 rs antagonism in CTZ.
 D/N cross BBB.
 D/N cause extrapyramidal SE.

25.  Domperidone & not metoclopramide is used
to counteract emesis d/t Levodopa WHY?
 Domperidone d/n cross BBB
& hence d/n block the therapeutic effect of levodopa.

26.  Headache
 Dryness of mouth
 Diarrhoea
 Rashes

27.  Same as metoclopramide.
 Not useful in chemotherapy induced vomiting.
 DOSE: 10-40 mg tds

28.  5HT4 agonist
myenteric plexus
 5HT3 antagonist
 D/N block D2 receptor
No antiemetic action.
No extrapyramidal SE
Not banned but considered unsafe as there are
chances of ventricular arrhythmias.

29.  D2 antagonistic action
 AntiChE ( Ach potentiating) activity
 Low affinity for 5HT4 receptors
 Less chances of arrhythmias
 SE: Diarrhoea, Galactorrhoea & Gynaecomastia
 No extrapyramidal SE

30.  Ondansetron
 Control cancer chemotherapy or
 Radiation induced vomiting.

31. Cytotoxic drugs / radiation
Cellular damage
Release of 5HT acts on 5HT3 rs in GIT
Impulses are sent to CTZ & NTS
EMESIS

32.  Blocks 5HT3 rs in
GIT
CTZ
NTS
Prevents vomiting
 Powerful antiemetic & can be given orally or IV

33.  Oral BA 60-70%
 t½ 3-5 hrs DOA 8-12 hrs

34.  Well tolerated
Headache
Dizziness
Constipation or Diarrhoea

35.  Chemotherapy induced vomiting : 8mg iv or oral
 Highly emetogenic chemotherapy: Slow IV infusion over
15 mins ;30 mins before chemotherapeutic infusion.
 Dexamethasone 8-20 mg IV
 Less emetogenic administered orally.
 Radiation induced vomiting
 Postoperative vomiting

36.  10 times more potent than ondansetron.
 Long t1/2 of 8-12 hrs
 1-3 mg diluted in 20-50 ml saline & infused IV over
5 mins before chemotherapy, repeated after 12 hrs.

37.  Blocks D2 receptor in CTZ.
 Labyrinthine suppressant.
 Indicated in vertigo associated with vomiting
 limiting features
1. Extrapyramidal SE
2. Muscle dystonias

38.  Aprepitant
 Activation of neurokinin receptor in CTZ & NTS
by substance P released due to emetogenic
chemotherapy & other stimuli plays a role
in the causation of vomiting

39.  Alternative antiemetic for moderately emetogenic
chemotherapy in patients who cannot tolerate
other antiemetics or are unresponsive to them.
 Hallucination, disorientation can occur
 Nabilone is another cannabinoid with antiemetic
property

40.  Corticosteroids are prescribed along with primary
antiemetic drugs like metoclopramide, ondansetron
for highly emetogenic anticancer regimens.
 Corticosteroid has anti-inflammatory action
& alleviates nausea & vomiting.

41. • These are substances intended to promote digestion
of food
1.Pepsin: Maybe used in gastric achylia(absence of
gastric juice) due to atrophic gastritis, gastric
carcinoma, pernicious anemia, etc.
2.Papain: It is a proteolytic enzyme obtained from
raw papaya. Its efficacy after oral ingestion is
doubtful

42. • It is a mixture of pancreatic enzymes
• It contains amylase, trypsin and lipase indicated in
chronic pancreatitis or exocrine pancreatic deficiency
states.
• It has to be used as enteric coated tablets or capsules
to protect the enzymes from being themselves
digested in stomach by pepsin

43. Thank You

44.  Pharmacology test will be held on 3rd June
2023.
 Date: 03/06/2023
 Timings: 11-12 am (1HR).
 Marks: 25marks.
 Portion: 1. Respiratory System
2. Blood
3. GIT