A Power point presentation on Emetics and antiemetics suitable for reading by undergraduate medical students

1. Dr. D. K. Brahma
Associate Professor
Department of Pharmacology
NEIGRIHMS, Shillong

2.  Emetic Response: Relaxation of fundus, body of stomach and also
the oesophageal sphincter and oesophagus – but contraction of
pylorus and duodenum – then rythmic contraction of diaphragm and
abdominal muscles - expulsion via mouth
 Centre: Medulla Oblongata
 Relay Centers: chemoreceptor trigger zone (CTZ) and nucleus tractus
solitarius (NTS)
 Afferent impulses: GIT, throat and other viscera
 Triggering agents: Blood borne drugs, mediators, hormones and
toxins etc. – clinically cytotoxic drugs and radiation
 Transmitter: 5-HT (enterochromaffin cells) – via 5HT3 receptor of
ENS – to vagal and spinal visceral neurones ----- to CTZ and NTS
 Spilling of 5-HT due to massive release – acts on CTZ

3.  Other mediators: H1, D2, 5HT3, Muscarinic M
and opioid μ etc. – expressed in CTZ and NTS
 Vestibular apparatus: generates impulses
◦ Body equilibrium disturbed
◦ Ototoxic drugs
 Mainly relayed by cerebellum to vomiting
centre – Muscarinic and H1 receptors
 Directly in higher centres: Bad smell, ghastly
sight, pain, fear etc. – drug cisplatin

4.  Drugs which induce vomiting
 Acts on CTZ: Apomorphine
 Acts reflexly and on CTZ: Ipecacuanha
 Apomorphine: Morphine derivative – semi-synthetic
– 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

5.  Salt water
• Warm water – mild emetic
• 2 spoonful of common salt in 1 pint of warm water
 Mustard seed
• 1 table spoonful ground mustard seeds in half-pin
of warm water
• Strong coffee is one of the best domestic
stimulants, especially after a narcotic poison

6.  In Corrosive poisoning – acid and alkali (why?)
 In CNS stimulant poisoning
 To unconscious patients
 In Morphine and Phenothiazine poisoning

7. 1. Anticholinergics: Hyoscine, Dicyclomine
2. H1 antihistaminics: Promethazine,
Diphenhydramine, Doxylamine, Cyclizine,
Meclizine and Cinnarazine
3. Neuroleptics (D2 blockers): Chlorpromazine,
Prochlorperazine and Haloperidol
4. Prokinetics: Metoclopramide, Domperidone,
Cisapride, Mosapride and Tegaserod
5. 5HT3 antagonists: Ondansetron, Granisetron
6. Others: Dexamethasone, Benzodiazepines and
Cannabinoids
7. Newer Ones: NK1 receptor antagonist -
Aprepitant

8.  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

9.  Primarily used in motion sickness, morning sickness and some
other vomiting in 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

10.  Motion Sickness: Anticholinergics are
preferred – followed by H1 Antihistaminics –
antidopaminergics do not work
 Morning Sickness: Preferably drugs should be
avoided – reassurance and dietary
modification
◦ Dicyclomine, promethazine or metoclopramide are
preferred at low doses

11.  Uses:
◦ Useful in drug induced post anaesthetic nausea and
vomiting
◦ Disease induced vomiting – Gastroenteritis, uraemia,
liver disease
◦ Cancer chemotherapy
◦ Radiation sickness (less)
◦ Morning sickness
 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

12.  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)

13. 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 interneurones and CTZ
/NTS
 Pharmacokinetics: Absorbed orally, crosses BBB and
placenta and secreted in milk. Conjugated in liver,
t1/2 = 4 – 6 Hrs.

14.  Stimuli – cause 5-HT release
 Stimulates extrinsic and intrinsic
pathway
 Via peripheral 5-HT3 receptors
 Extrinsic pathway – via vagus
and dorsal root ganglia – CNS -
vomiting stimulation –
ondansetron
 Intrinsic pathway – excitatory
and inhibitory interneurones co-ordinates
peristalsis
◦ Contraction of proximal and
relaxation of distal gut muscles
◦ Ach/CGRP and NANC (NO)
◦ Prokinetics (Meto and Csprd) –
activates prejunctional 5-HT4 –
promote release of Ach/CGRP –
contractile activity
◦ Also weak 5-HT3 blocking action
(inhibitory neurones)
◦ Meto and Csprd also inhibits D2
action normally D2 acts as releaser
of Ach – more contraction with Meto

15.  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

16.  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
 Read yourself (Prokinetics) – Cisapride, mosapride, Itopride etc.

17.  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
 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.

18.  ADRs: Headache and dizziness. Mild
constipation and abdominal discomfort.
Hypotension, allergic reactions, chest pain
and bradycardia etc.
 Other Drugs: Granisetron, Palonosetron and
Ramosetron etc. – READ YOURSELF

19.  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.

20.  Corticosteroids, Benzodiazepines and
cannabinoides