vomitting drugs

1. Emetics ,Antiemetics
Prokinetic Agents
Dr. Akshil Mehta

2. Physiology of Vomiting
• Stimulation of vomiting centre in medulla
oblongata
• It receives afferents from
 CTZ
vestibular apparatus
GI tract
Centres in the Brain

3. Physiology of Vomiting
Cytotoxic drugs / radiation
Damage cells , irritate the gut mucosa
Release mediators from gut mucosa
Activation of vagal afferents in the gut
Emetogenic impulses to NTS,CTZ
Stimulate Emetic centre
Vomiting

4. Emetics
Apomorphine :
• Derivative of morphine
• Given SC/IM
• Produces vomiting in 5-10 min
• Stimulates dopaminergic Rs in CTZ
• Depresses Respiration ..so should be avoided
in presence of respiratory depression

5. Emetics contd.
Ipecacuanha
• Obtained from the dried roots of Cephalis
Ipecacuanha which contains an alkaloid emetine .
• Given as syrup 15- 20 ml  vomiting in 15
minutes
• Acts
Directly on CTZ
Reflexly by irritating the gastric mucosa
• Safe in Children

6. Drugs that produce Emesis
• Most cancer drugs
• Levodopa , bromocriptine, other dopamine
agonists
• Morphine and opioids
• Cholinomimetic drugs
• Metronidazole
• Ergot alkaloids
• Chloroquine, emetine

7. Antiemesis
• Vomiting is a protective mechanism.
• Aimed at eliminating the unwanted harmful
material from the stomach .
• In dehydration , weakness and electrolyte
imbalance .. Vomiting needs to be suppressed
with drugs

8. Antiemetic Classification
• Dopamine D2 antagonists – ( prokinetics )
 Metaclopromide , domperidone , trimethobenamide
• 5HT3 antagonists
 Ondansetron, granisetron, dolasetron
 Tropisetron, palanosetron
• Antimuscarinics
 Hyoscine, Promethazine
 Cyclizine , diphenhydramine
• Neuroleptics
 Chlorpromazine, prochlorperazine
 Haloperidol
• Neurokinin Rs antagonists
 Aprepitant
 Forprepitant
• Other Agents
 Cisapride , corticosteriods
 Cannabinoids – dronabinol, nabilone

9. Dopamine D2 Antagonists
• Metoclopramide and domperidone act
centrally by blocking dopamine D2 Rs in the
CTZ and thereby prevent vomiting .
They enhance the tone of the LES and
increase gastric peristalsis … Prokinetics
• Trimethobenzamide has antihistaminic
activity in addition to dopamine blockade

10. 5HT3 Antagonists
• Blocks 5 HT3 rs in the gut , CTZ and NTS.
• Efficient Antiemetics
• Effective both orally and parenterally
• Largely safe – no sedation or other CNS/
autonomic side effects .
• Adverse effects negligible – headache , GI
disturbances .
• Drugs of choice in postoperative and anticancer
drug- induced vomiting

11. Pharmacokinetics
• 5 HT3 are well absorbed from the gut
• Metabolised by the liver by microsomal
enzymes
• Excreted by the kidneys and partly through
the gut .
• They can be given orally , IM and IV .
• Dose reduction may be required in liver
dysfunction

12. Adverse Effects
• Headache
• Constipation
• Abdominal discomfort
• Rashes
• Dolesetron prolongs QT interval and so should
be avoided in patients with prolonged QT
interval .

13. Uses
• To control vomiting induced by anticancer
drugs or radiotherapy .
IV 30 min before or orally 1 hr before starting
chemotherapy . ( ondansetron 8 mg infusion over
15 min. From 2 nd day.. 8mg orally for 3-7 days ).
• Postoperative vomiting and other drug
induced vomiting (but not in motion sickness )
In pov 4-8mg ondansetron before induction and
the dose may be repeated after 8 hr or as required

14. Ondansetron
• Oral bioavailability is 60 – 70 %
• T ½ of 3- 5 hr and a duration of action of 4 -12 hr.
• Dose 4-24 mg in one / 2 divided doses
• Emset , Osteron 4, 8 mg tab 2mg/ml inj.
Palanosetron has a higher affinity for the 5 HT3 rs
longer t ½

15. Granisetron
• More potent than ondansetron as an
antiemetic
• Though Granisetron , Dolasetron and
Topisetron have longer t ½, their biological t ½
remains the same .
Dose: Granisetron 1-2 mg OD . 10 μg /kg IV .
GRANISET 1,2 mg tab . 1mg /ml/inj.

16. Drugs for vomiting due to various causes
Conditions Drugs
Motion sickness Hyoscine , cyclizine , Promethazine ,
Cinnarizine
Vomiting due to
cytotoxic drugs
1. Ondansetron + Dexamethsone +
aprepitant
2. Metoclopramide + dexamethasone +
diphenhydramine + lorezepam
Vomiting due to
other drugs
Chlorpromazine , Metoclopramide
Postoperative
vomiting
Ondansetron , Metoclopramide
Vomiting in
Pregnancy
Doxylamine , Dicyclomine , pyridoxine ,
cyclizine , meclizine , Metoclopramide

17. The stimuli , pathways and centre mediating emetic
reflex and Rs involved
Fear emotion,
Anticipation , Smell,
sight
Higher Centres
Emetic
Centre Cerebellum
Inner
Ear
NTS, 5 HT3 ,
D2, M3, H1
CTZ, (Area postrema ),
5 HT3, D2 , M1
Pharynx Stomach , Small intestines ( 5 HT3)
Toxins , Drugs , Irritants

18. Anti Muscarinics
Hyosine
• It is a labyrinthine sedative very effective in motion
sickness( due to over stimulation of vestibular
apparatus along with psychological environmental
factors ).
• It relaxes the gastrointestinal smooth muscle.
• Taken 30 min before journey ,( 0.4 – 0.6 mg oral)
acts for 6 hrs and the dose should be repeated if the
journey is longer than that .
• A transdermal patch delivers hyoscine constantly
over 3 days and is to be applied behind the ear .
• Sedation and dry mouth are common side effects .

19. • Dicyclomine : is used to control vomiting in
morning sickness and motion sickness – orally
in the dose of 10 -20 mg .
• H1 antihistamine : Like promethazine ,
diphenhydramine , doxylamine , cyclizine and
cinnarizine have ant cholinergic properties
.Antihistamines block H1 rs in the area
postrema as well as muscarinic rs in the CNS
.they also act in GIT. Useful in motion sickness
and post operative vomiting .

20. Doxylamine
• Available in combination with pyridoxine for
morning sickness .
• Free of teratogenic potential but its safety is
not proved .
• Dose : 10 mg + pyridoxine 10mg GRAVIDOX.
DOXINATE 10 mg tab.

21. Neuroleptics
• Blocks D2 rs in the CTZ
• Useful in vomiting due to most causes except
motion sickness
• Common side effects :Sedation and extra
pyramidal symptoms .
• Prochlorperazine is anti emetic as well useful
in vomiting with vertigo.Dose ( 5- 25 mg .
STEMETIL 5 , 25mg tab , 12.5 mg /ml Inj.

22. Neurokinin Rs Antagonists
These drugs bind to Neurokinin (nk1) rs in the
area postrema and act as anti emetics .
Aprepitant available for oral use while
fosaprepitant is given IV and gets converted to
aprepitant in the body .Has a t ½ of 12 hr . It is
metabolised in the liver by microsomal
enzymes CYP3A4 and may compare with other
drugs metabolised by the same pathways .

23. NK1 antagonist may cause dizziness , weakness
and diarrhoea .
NK1 antagonist used for prevention of
chemotherapy induced vomiting in
combination with 5 HT3 antagonists and a
glucocorticoid.
Dose : Aprepiant 125mg 1 hr before
chemotherapy followed by 80mg daily for next
days .

24. Corticosteroids
• used in combination with other antiemetics like
ondansetron or metoclopramide .
• Controls delayed vomiting following anti cancer
drug therapy .
• Act by activating the glucocorticoid rs in the NTS .
Pyridoxine ( Vitamin B6 )
• Used as prevention of vomiting in pregnancy
without any known pharmacological basis .
• Serves as a co factor in GABA synthesis and GABA
acting as the inhibitory neurotranmitter at CTZ
may suppress vomiting .
• Dose 20 – 60 mg

25. Sedatives hypnotics :
• Barbiturates and benzodiazipines may raise
the threshold for vomiting by depressing the
CNS .
• Their anxiolytic and sedative properties also
help.
• Used as a adjuvants to other antiemetics in
treating anticancer drug – inducing vomiting .

26. Cannabinoids :
• Dronabinol , a cannabiniod is 9 tetra
hydrocannabinol.
• It has antiemetic properties
• Acts by the stimulation of the Cannabinoid rs
(CB1 ) in the vomiting centre .
• It also increases appetite
Dronabinol is orally effective and almost
completely absorbed on oral administration
Dose 5mg/ m2, 2 hr before chemotherapy and
the dose may be repeated every 4 hr

27. • Dronabinol : causes hallucinations , euphoria
, dysphoria , behavioural abnormalities ,
dependence , incresed appetite , dryness of
mouth and hypotension .
• Can be used as an alternative in the
prevention of anticancer drug induced
vomiting in combination with other anti
emetics – when the other drugs are ineffective
.
Also usedas an appatite stimulant.