The document discusses the mechanisms and pharmacology of vomiting and its treatment, highlighting the emetic response and the role of various neurotransmitters and receptors involved in this process. It outlines different emetic agents and medications that can induce or prevent vomiting, including their mechanisms of action, indications, dosing, and adverse effects. Additionally, it categorizes drugs based on their use in conditions like motion sickness, chemotherapy-induced nausea, and other vomiting disorders.

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