The document discusses 5 case scenarios involving the use of anti-emetic drugs and presents information on the classification and mechanisms of action of common anti-emetic medications. It describes how metoclopramide, dicyclomine, promethazine and other drugs work by blocking receptors involved in vomiting pathways in the brain and gastrointestinal tract. The last case scenario discusses a child who developed dystonia after being given an anti-emetic, likely metoclopramide, indicating its potential side effect.

1. A little brain teaser….
• Case Scenario 1:
• A 45 years male, having history of oral cancer is under chemotherapy
• He has been co-prescribed with metoclopramide as a prophylaxis for
chemotherapy induced nausea and vomiting
• Case Scenario 2:
• A 5 years child is about to travel to a hill station. As he feels sick every time he
travels, he was given dicyclomine as a prophylactic
• Case Scenario 3:
• A 28 years female, primigravida, visited to general practitioner for nausea and
vomiting in early morning. The doctor prescribed her promethazine

2. A little brain teaser….
• Case Scenario 4:
• A 6 month child presented in your OPD for some dental procedure. Following
the procedure, he somehow starts to have vomiting.
• To control the new symptom, you have prescribed him some anti-emetic.
• The mother of the child returns to you with complains of abnormal tone of
the limbs (dystonia)
• Which drug could have lead to this symptom?
• Case Scenario 5:
• You are planning to go on a cruise with your friends, but you are afraid of
having sea sickness. What drug would you use as a prophylactic?

3. Anti-emetics
Dr. Pravin Prasad
MBBS, MD Clinical Pharmacology
Assistant Professor, Department of Clinical Pharmacology
Maharajgunj Medical Campus
20 February 2020 (8 Falgun 2076)

4. By the end of this discussion, BDS 2nd year
students will be able to:
• Outline the neural mechanism and chemicals involved in
vomiting
• Classify drugs used as anti-emetics
• Explain the therapeutic basis of different drugs used as ant-
emetics

5. Neural circuits leading to vomiting
Ototoxic drugs

6. Neural circuits leading to vomiting
• Receptors and endogenous
chemicals responsible:
• Serotonin (5-HT) on 5-HT3
receptors
• Histamine on H1 receptors
• Dopamine on D2 receptors
• Acetylcholine on M receptors
• Substance P on NK1 receptors
• Cannabinoid on CB1 receptors
• Opioids on μ receptors
Ototoxic drugs

7. Vomiting pathways with pharmacological
twist!!

8. Anti-emetics: Classification
Class Examples
Anitcholinergics Hyoscine, Dicyclomine, Cyclizine
H1 antihistaminics Promethazine, Diphenhydramine, Dimenhydrinate,
Doxylamine, Meclozine, Cinnarazine
Neuroleptics (D2 blockers) Chlorpromazine, Triflupromazine, Prochlorperazine
Prokinetic drugs Metoclopramide, Domperidone
5-HT3 antagonists Ondansetron, Granisetron
NK1 antagonists Aprepitant
Adjuvant antiemetics Dexamethasone, Benzodiazepines

9. Anti-cholinergic drugs as antiemetics
• Hyoscine, Dicyclomine, Cyclizine
• Acts by blocking cholinergic transmission of nerve impulse from
vestibular apparatus to vomiting center
• Dicyclomine: additional direct smooth muscle relaxation
• Effective in vomiting due to motion sickness
• Should be given prophylactically
• Action lasts for 4-6 hours (hyoscine), transdermal patch acts for 3 days
• Dicyclomine also used for morning sickness (pregnancy)
• Side effects: dry mouth, sedation
• Should be avoided in children below 6 months

10. H1 anti-histaminic as anti-emetics
• Promethazine, Diphenhydramine, Dimenhydrinate, Doxylamine,
Meclozine, Cinnarazine
• Anti-emetic action exerted by:
• Anticholinergic, antihistaminic action
• Additional weak anti-dopaminergic and sedative properties
• Also blocks extrapyramidal side effects of metoclopramide
• Mainly useful in motion sickness
• Effective for 4-6 hours
• Also used in morning sickness*, chemotherapy induced nausea and
vomiting (in combination with metoclopramide)
• Side effects: sedation, dryness of mouth

11. Neuroleptics (D2 blockers) as anti-emetics
• Chlorpromazine, Triflupromazine, Prochlorperazine
• Older D2 blockers: potent anti-emetics
• Acts by blocking D2 receptors in CTZ
• Additional anti-muscuranic, anti-histaminic action
• Prochlorperazine: labyrinthine suppressant (anti-vertigo as well)
• Useful in:
• Drug induced, post-operative nausea and vomiting
• Disease induced vomiting: gastroenteritis, uraemia, liver disease, migraine
• Malignancy associated and cancer chemotherapy induced N/V
• Radiation sickness vomiting
• Hyperemesis gravidarum
• Side effects: sedation, acute muscle dystonia (children, girls), other
extrapyramidal side effects

12. Prokinetic drugs as anti-emetics
• Metoclopramide, Domperidone
• Acts by:
• Serotonin agonism at 5-HT4 receptors
• Increased ACh release from
myenteric motor neurons
• Faster gastric emptying
• Enhanced lower oesophageal
sphincter tone

13. Prokinetic drugs as anti-emetics
• Metoclopramide, Domperidone
• Acts by:
• D2 antagonism: blocks action of dopamine
leading to-
• Increased ACh release in the GIT
• Faster gastric emptying
• Enhanced lower oesophageal
sphincter tone
• Direct blockade of Dopamine action of
area postrema  decreased impulses to
vomiting centre
• Mechanism of action for domperidone

14. Prokinetic drugs as anti-emetics
• Metoclopramide, Domperidone
• Acts by:
• Serotonin antagonism at 5-HT3
receptors
• Present at inhibitory myenteric
interneurons and NTS/CTZ
• Peripheral action: minor role
• Central action: significant when
large doses are used to control
CINV

15. Prokinetic drugs as anti-emetics
Pharmacokinetics:
• Metoclopramide:
• Crosses blood brain barrier
• Crosses placenta
• Secreted in milk
• Action starts in 0.5 – 1 hr (oral), 10 mins (i.m.) 2 mins (i.v.), lasts for 4-6 hours
• Domperidone:
• Poor oral bioavailability
• Crosses blood-brain barrier poorly
• Plasma half life: 7.5 hrs

16. Prokinetic drugs as anti-emetics
Indications:
• Metoclopramide:
• Anti-emetic: post operative, drug induced, disease associated, radiation
sickness
• As gastrokinetic agent
• Dyspepsia and other functional g.i. disorders (persistent hiccups)
• Gastroesophageal reflux disease: as adjuvant
• Domperidone:
• Similar to metoclopramide
• Less effective gastrokinetic and not useful in highly emetogenic chemotherapy
• Levodopa/ bromocriptine induced vomiting in PD

17. Prokinetic drugs as anti-emetics
Side effects:
• Metoclopramide:
• Sedation, dizziness, loose stools, muscle dystonia (children)
• Long term use: Parkinson’s Disease, galactorrhoea, gynaecomastia
• Effects may be seen in suckling infant
• Domperidone:
• Cardiac arrhythmia on rapid i.v. injection
• Dry mouth, loose stools, headache, rashes, galactorrhoea: mild

18. Conclusion
• Vomiting is synchronized by an orchestra of chemicals through
multiple neural mechanisms
• Seven classes of drugs are used for the treatment of vomiting
• Anticholinergic and anti-histaminic agents are used mainly for motion
sickness and morning sickness; neuroleptics and prokinetics are used
for vomiting due to multiple causes