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Emetics and antiemetics
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
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.