emetics and antiemetics medicine

1. EMETICS & ANTIEMETICS
Dr Chinmaya Debasis Panda
MBBS,MD

2. Emesis:
• A protective reflex that serves to rid the stomach and
intestine of toxic substances and prevent their further
ingestion.
• Vomiting consists of:
Pre-ejection phase: gastric relaxation & retroperistalsis
Retching: rhythmic action of respiratory muscles preceding
vomiting and consisting of contraction of abdominal and
intercostal muscles and diaphragm against a closed glottis
Ejection: intense contraction of the abdominal muscles and
relaxation of the upper esophageal sphincter

3. Neuronal path:
• Centre: lateral reticular formation of Medulla Oblongata
• Relay Centres: chemoreceptor trigger zone (CTZ) and nucleus
tractus solitarius (NTS)
• Afferent impulses: GIT, throat (vagus via NTS), other viscera
(spinal cord), cerebral cortex (anticipatory) & vestibular
apparatus(motion sickness)

5. Receptors:
CTZ:
• serotonin(5-HT3),
• dopamine (D2),
• and opioids(µ)
NTS:
• enkephalin,
• Histamine(H1),
• Ach(M),
• and also contains 5-HT3
Also neurokinin(NK1 activated by substance-p), cannabinoid(CB1)

6. Path:
Exposure to Cytotoxic drugs, radiation and other g.i. irritants
release 5-HT from enterochromaffin cells
Acts on 5-HT3 receptors present on extrinsic primary afferent neurones
(PAN) of the enteric nervous system (ENS)
with vagal and spinal visceral afferents impulses reach NTS and CTZ
Vomiting
5-HT may also spill into circulation and reach CTZ via the vascular
route

8. Emetics:
• Drugs which induce vomiting
• Acts on CTZ: Apomorphine
• Acts reflexly and on CTZ: Ipecacuanha
Apomorphine: Morphine derivative – semisynthetic – Dopaminergic agonist in CTZ
• 6 mg IM/SC – acts within 5 minutes
• Respiratory depression
• Orally – not recommended (large dose – slow inconsistent)
• Parkinsonism
Ipecacuanha: Cephaelais ipecacuanha
• Syrup ipecac – 15 to 30 ml (10 to 15 in child)
• Action takes 15 minutes
• MOA: Irritation of Gastric mucosa and directly on CTZ
Also salt water, mustard seed

9. Contraindications:
Corrosive poisoning
CNS stimulant drug poisoning
Kerosine(petroleum product) poisoning
Unconsious patients
Morphine or phenothiazine poisoning

10. ANTIEMETICS:
1. Anticholinergics : Hyoscine, Dicyclomine
2. H1 antihistaminics: Promethazine, Diphenhydramine, Dimenhydrinate,
Doxylamine, Meclozine (Meclizine), Cinnarizine.
3. Neuroleptics (D2 blockers): Chlorpromazine, Triflupromazine,
Prochlorperazine, Haloperidol, etc.
4. Prokinetic drugs: Metoclopramide, Domperidone, Cisapride,
Mosapride, Itopride
5. 5-HT3 antagonists: Ondansetron, Granisetron, Palonosetron,
Ramosetron
6. NK1 receptor antagonists: Aprepitant, Fosaprepitant
7. Adjuvant antiemetics: Dexamethasone, Benzodiazepines, Dronabinol,
Nabilone

11. Anticholinergics:
Hyoscine: Motion Sickness (0.2 to 0.4 mg IM)
• Used IM/SC, but short duration of action
• MOA: Blocking of cholinergic link of vestibular apparatus to
the vomiting centre – does not work in vomiting due to other
aetiology
• ADRs: Sedation, dry mouth and other anticholinergic effects
• Transdermal delivery system (1.5 mg)
Dicyclomine: Prophylaxis of motion sickness and morning
sickness

12. H1 ANTIHISTAMINICS:
• Primarily used in motion sickness, morning sickness and some other
vomiting to lesser extent –
• Also anticholinergic, antihistaminic and antidopaminergic actions
• Promethazine (Phenothiazine), diphenhydramine: 4 – 6 Hours
protection
• Combined with metoclopramide in CINV: additive effect plus counters
extra pyramidal effects
• Promethazine theoclate (Avomine) – motion sickness
• Doxylamine: Sedative H1 antihistaminic – marketed in combination
with Pyridoxine – specifically for morning sickness – duration of
action 10 Hours (at bed time) – drowsiness, dry mouth, vertigo
• Meclizine: Long duration of action – sea sickness
• Cinnarizine: anti vertigo action – inhibits Ca++ influx in endolymph

13. Motion Sickness:
Anticholinergics & H1 Antihistaminics are preferred
antidopaminergics do not work
Morning Sickness:
Preferably drugs should be avoided
Reassurance and dietary modification tried first
Dicyclomine, promethazine or metoclopramide are preferred at low
doses

14. Neuroleptics: (phenothiazines, haloperidol)
Uses:
• Drug induced and postoperative nausea and vomiting (PONV).
• Disease induced vomiting: gastroenteritis, uraemia, liver disease, migraine,
etc.
• Malignancy associated and cancer chemotherapy (mildly emetogenic)
induced vomiting.
• Radiation sickness vomiting (less effective).
• Morning sickness: should not be used except in hyperemesis gravidarum.
ADRs: Sedation, acute muscle dystonia (diagnose the cause first before
administering)
• Prochlorperazine (Stemetil) – D2 blocking agent - labyrinthine suppressant
– antivertigo and antiemetic action. Effective in CINV with vertigo
• EPS and muscle dystonia

15. PROKINETIC DRUGS: Metoclopramide
Actions on GIT: On upper GIT – Increases gastric peristalsis
• Relaxes pylorus and 1st part of duodenum – better gastric emptying
• LES tone increased – also increases Intestinal peristalsis
Actions on CNS: Acts on CNS – can counter Apomorphine induced
vomiting
• Gastrokinetic action contributes
• No antipsychotic property, but has extra pyramidal and prolactin
secreting effects (Promethazine context)

16. MOA:
1. D2 antagonism: Dopamine is inhibitory transmitter via D2
receptor – delays gastric emptying – also relaxation of LES –
nausea and vomiting – Metoclopramide causes opposite
effect
• Also central antidopaminergic action
2. 5-HT4 agonism: enhanced Acetylcholine release in
myenteric plexus – gastric hurrying and increased LES tone
3. 5-HT3 antagonism: at high concentration
• Blocks at inhibitory myenteric interneurons and CTZ/NTS
Pharmacokinetics: Absorbed orally, crosses BBB and
placenta and secreted in milk. Conjugated in liver, t1/2 = 4 –
6 Hrs.

18. Conntd.
ADRs: Sedation, dizziness, loose stool and muscle dystonia
• Long use: Parkinsonism, galactorrhoea, gynaecomastia
• Safe in pregnancy but in lactating mother children may have loose stool,
dystonia etc. DI – abolishes levodopa action
Uses:
• Antiemetic: Postoperative, drug induced, disease associated, radiation
induced etc. but not effective in motion sickness. Still preferred in vomiting
due to anticancer drug – in combination with Promethazine
• Gastrokinetic: To accelerate gastric emptying – Emergency GA,
gastroparesis (post vagotomy), duodenal intubation etc.
• Dyspepsia: stops hiccup
• GERD: Does not aid in healing, PPIs are preferred – used as adjuvant

19. Domperidone:
• Chemically related to haloperidol but action like Metoclopramide
• D2 antagonist – in upper GIT (not attenuated by atropine)
• Rarely EP side effect – does not cross BBB, but hyperprolactinemia occurs
• Acts mainly through CTZ – outside BBB
• Does not abolish action of levodopa
• Kinetics: absorbed orally but 15% bioavailability – high 1st pass
metabolism, completely metabolized and excreted in urine.T1/2 – 7 – 8 Hrs
• ADRs: Less than Metoclopramide – dry mouth, loose stool, headache,
galactorrhoea etc. Arrhythmia on injection
• Uses: Similar as Metoclopramide but milder spectrum of action –not
effective in chemotherapy

20. Cisapride:
• Lacks D2 receptor action(no antiemetic action)
• Fascilitate motility throughout the GI tract(also colon)
• Also 5-HT4 mediated Cl– secretion in the colon- loose stool
• Prolongs QTc- not marketed now
Mosapride:
• Relatively safer
Itopride:
• D2 and Ach receptor blocking action, less 5HT4 affinity.
• Lack QTc prolongation and metabolized by flavin monooxigenases
• safer

21. 5-HT3 ANTAGONISTS: Ondansetron
• Developed for Chemotherapy/radiotherapy induced vomiting – also
effective in others (PONV)
• MOA: Acts peripherally as well as centrally – Blocks depolarizing
action of 5-HT3 receptors in vagus at GIT and CTZ/NTS
• No action on Dopamine receptor – does not block Apomorphine
induced vomiting and mild gastrokinetic effect
• Kinetics: 60 – 70% bioavailability – first pass metabolism.
• Metabolized as glucoronide and sulfate. Eliminated in urine and
faeces. T1/2 life 5-7 Hrs

22. • Dose: 8 mg slow IV for 15 minutes ½ hr before
chemotherapy. Followed by 2 such doses 4 hours apart. Then
8 mg orally twice daily for 1 week. For others 4 – 8 mg IV
followed by every 8 hourly.
• 80% success – better/equal to Metoclopramide – no dystonia
or sedation. Adjuvant improve response.
• ADRs: Headache and dizziness. Mild constipation and
abdominal discomfort. Hypotension, allergic reactions, chest
pain and bradycardia etc.
Granisetron: 10 times more potent, Palonosetron: longest
acting and highest affinity for 5-HT3 receptor(t1/2-40hrs)

23. NK 1 receptor antagonists:
Aprepitant: Newer antiemetic
MOA: Emetogenic chemotherapy releases Substance P – stimulates CTZ
and NTS by acting on NK1 - blocking of NK1 receptors causes emesis
blocking
• Little effect on 5-HT3 or D2 receptor
• GIT motility not affected
Uses: 125 mg + 80 mg + 80 mg for 3 days with IV Ondansetron and
Dexamethasone – for cisplatin induced vomiting – useful in multiple
cycle patients – Orally 40 mg can be used for PONV
• Kinetics: well absorbed orally, metabolized in liver, excreted in faeces
and urine. T1/2 10 – 13 Hrs
• ADRs: Weakness, fatigue, flatulence etc.

24. ADJUVANT ANTIEMETICS:
Corticosteroids: through anti-inflammatory action, also reduce side
effects of other antiemetics
Benzodiazepines: Through sedative action, reduce psychogenic
component and suppress dystonic side effects of others
Cannabinoids: CB1 receptors on CTZ and vomiting center
e.g: dronabinol, nabilone

25. T
H
A
N
K
Y
O
U