2. Vomiting:- Expulsion of gastric contents through
mouth due to mass antiperistalsis
Nausea:- An uneasy feeling in anticipation of vomiting
Retching:- Series of weaker and unproductive vomiting
movement
2
Dr Anuj
3. Vomiting results due to stimulation of vomiting centre
(VC) which is located in lateral medullary reticular
formation
3Dr Anuj
5. VC recieves input from GI mucosa, Chemoreceptor
trigger zone(CTZ), and vestibular apparatus.
Efferents fibre from this centre when stimulated ,
cause stimulation of phrenic nerve supplying to
diaphragm and of somatic nerve supplying the
abdominal muscles to promote emesis
5Dr Anuj
6. Irritation of GI mucosa by drugs or irritants leads to
release of serotonin that stimulates VC via 5HT3
receptors
CTZ is rich in dopamine D2 and serotonin 5HT3 and
neurokinin NK1 receptor
Motion sickness occurs due to stimulation of
vestibular apparatus and cerebellum, these structures
result in stimulation of VC by activating M1& H1
receptors
By stimulation of H1 receptors histamine play a
permissive role in all types of vomiting
6Dr Anuj
7. Vomiting centre
(medulla)
Cerebral cortex
Anticipatory emesis
Smell
Sight
Thought
Vestibular
nucleiMotion
sickness
Pharynx & GIT
Chemo & radio therapy
Gastroenteritis
Chemoreceptor
Trigger Zone
(CTZ)
(Outside BBB)
Cancer chemotherapy
Opioids
Muscarinic, 5 HT3 &
Histaminic H1
5 HT3 receptors
Dopamine D2
5 HT3,,Opioid
Receptors
Muscarinic
Histaminic H1
Pathophysiology of Emesis
7Dr Anuj
8. Now answer this question
Which group of drugs can be used as antiemetics ?
Serotonin 5 HT3 Antagonists
Dopamine D2 Antagonist
Anticholinergics
H1 Antihistaminics
Cannabinoids
8Dr Anuj
10. Serotonin 5 HT3 Antagonist
Potent antiemetics
Even though 5 HT3 receptors are present in vomiting
centre & CTZ, the antiemetic action is restricted to
emesis caused by vagal stimulation.
High first pass metabolism
Excreted by liver & kidney
No dose reduction in renal insufficiency but needed in
hepatic insufficiency
Given once or twice daily – orally or intravenously.
10Dr Anuj
11. Drugs Available
Ondansetron (ONDEM) 32 mg / day
Granisetron (GRANISET) 10 mg / kg / day
Dolasetron 1.8 mg / kg / day
Palonosetron 250µg by slow iv inj 30 min before chemo
Indications
Chemotherapy induced nausea & vomiting – given 30
min. before chemotherapy.
Postoperative & postradiation nausea & vomiting
11Dr Anuj
12. Adverse Effects
Excellent safety profile
Headache & constipation
All three drugs cause prolongation of QT interval, but
more pronounced with dolasetron.
Palonosetron :- longest acting 5HT3 receptor blocker
with highest affinity for 5HT3 receptor (t1/2=40 hrs)
Rapid i.v. injection causes blurring of vision
12Dr Anuj
13. Dopamine D2 Antagonist
Antagonise D2 receptors in CTZ.
Drugs available
Metoclopramide(PERINORM, REGLAN) 2.5 mg b.d
Domperidone(DOMSTAL) 10 mg b.d
Both drugs are also prokinetic agents due to their 5
HT4 agonist activity.
Domperidone – oral ; Metoclopramide – oral & i.v
Metoclopramide crosses BBB but domperidone cannot.
13Dr Anuj
14. Now answer this question
Which is a better antiemetic – Metoclopramide or
Domperidone ?
As CTZ is outside BBB both have antiemetic effects.
But as metoclopramide crosses BBB it has adverse
effects like extrapyramidal side effects..
Domperidone is well tolerated.
14Dr Anuj
15. Neuroleptics
: Phenothiazines & Butyrophenones
Phenothiazines
Prochlorperazine( STEMETIL)
Promethazine ( AVOMINE)
Phenothiazines are antipsychotics with potent
antiemetic property due to D2 antagonism.
Butyrophenone
Droperidol(DROPEROL)
Droperidol used for postop. nausea & vomiting, but
cause QT prolongation.
15Dr Anuj
16. H1 Antihistaminics
Most effective drugs for motion sickness
Drugs available
Meclizine
Cyclizine
Dimenhydrinate
Diphenydramine
Promethazine – Used in pregnancy, used by
NASA for space motion sickness
16Dr Anuj
17. Anticholinergics
Scopolamine (hyoscine) – used as transdermal patch
for motion sickness
Cannabinoids
Dronabinol & Nabilone are analogues of delta-9-THC, an active
principle of cannabis sativa.
Probably act by stimulating CB1 subtype of cannabinoid receptor
present in neurons around vomiting centre
Dronabinol – used as adjuvant in chemotherapy induced vomiting. It is
a psychoactive substance
Nabilone
17Dr Anuj
18. NK1 receptor antagonist
Aprepitant :-
selective high affinity NK1 receptor antagonist that
blocks the emetic action of substance P
For pt undergoing multiple cycles of chemotherapy
Well absorbed orally and penetrates BBB
Metabolised in liver by CYP3A4
S/E weakness fatigue flatulence rise in liver enzymes
Dr Anuj 18
19. Now answer this question
A physician prescribed Tab.Ondansetron for prophylaxis of motion sickness. Even
though ondansetron is a potent antiemetic it didn’t produce any effect in this
patient. Can you explain why ?
19Dr Anuj
26. Some more questions
Vitamin used for tt of Morning sickness
Pyridoxine (Vitamin B6)
Antivertigo drug having antimotion sickness property
Cinnarizine
Labyrinthine suppressant having selective antivertigo
and antiemetic action
Prochlorperazine
Blurring of vision caused by
Rapid iv inj of palonosetron
Dr Anuj 26
